pnCnpmmattCbscwf

●

●

●

tliTws

●

●

●

A

EXECUTIVE SUMMARY

●

●

rGddqilstthtcttarmtdortaptcpog

pha

INTRODUCTION

Regular evaluation of nutritional status androvision of adequate nutrition are key compo-ents in the overall management of children withKD. The traditional and predominant focus ofutritional management for children with im-aired kidney function is to prevent the develop-ent of PEM and meet the patient’s vitamin andineral needs. More recently, overnutrition char-

cterized by obesity and the long-term implica-ions of unbalanced dietary and lifestyle prac-ices are of increasing concern to the pediatricKD population, and attention to this issue muste incorporated into the nutrition managementcheme. Thus, the focus of nutritional care forhildren across the spectrum of CKD must al-ays be centered on the achievement of the

ollowing goals:

Maintenance of an optimal nutritional status(ie, achievement of a normal pattern of growthand body composition by intake of appropri-ate amounts and types of nutrients).Avoidance of uremic toxicity, metabolic abnor-malities, and malnutrition.Reduction of the risk of chronic morbiditiesand mortality in adulthood.

This publication represents the first revision ofhe K/DOQI Pediatric Clinical Practice Guide-ines for Nutrition in Chronic Renal Failure ands a completely revised and expanded document.he revision of the document published in 2000as considered necessary for the following rea-

ons:

To modify prior guideline statements basedupon the availability of information publishedsubsequent to the development of the 2000guidelines.To expand the target population with recom-mendations to address patients with CKDstages 2 to 5 and kidney transplant recipients,in addition to the dialysis population ad-dressed in the prior publication.To address a variety of topics not covered inthe original guidelines, such as the dietarymodification of sodium, potassium, fluid, cal-cium, and phosphorus, all of which can have a

profound impact on patient outcomes.

merican Journal of Kidney Diseases, Vol 53, No 3, Suppl 2 (Marc

To incorporate references to dietary recommen-dations, anthropometric reference values, andgrowth charts for the healthy population thatreplaced those on which the 2000 guidelineswere based.To reconcile discrepancies in recommenda-tions for nutrient modification that exist be-tween the pediatric nutrition guidelines andrecent KDOQI guidelines on Hypertensionand Dialysis Adequacy.

One of the challenges for the Work Group inevising the 2000 K/DOQI Pediatric Nutritionuidelines was the remarkable lack of publishedata available for the topic of nutrition in chil-ren with all stages of CKD. In addition, theuality of evidence in pediatric nephrology stud-es related to the issues addressed in these guide-ines was frequently low due to small sampleize, the lack of randomized controlled trials, andhe lack of information for both short- and long-erm clinical outcomes. Thus, the Work Groupas generated a set of guideline recommenda-ions to provide guidance to practitioners on thelinical aspects of nutrition management while athe same time recognizing the limited evidencehat exists. These recommendations are based onvailable evidence, such as it exists; they alsoely heavily on the opinion of the Work Groupembers and are graded accordingly. All submit-

ed suggestions from physicians, nurses, andietitians who participated in the public reviewf the draft recommendations were carefullyeviewed and considered for incorporation intohe recommendations by the Work Group Chairsnd individual Work Group members. Most im-ortantly, the absence of randomized controlledrials to support the recommendations made pre-ludes the subsequent development of clinicalerformance measurements by oversight bodiesn most, if not all, of the issues addressed by theuidelines.The process of revising the guidelines has also

rovided a unique opportunity to detect andighlight deficiencies in the scientific literaturend to identify much needed areas of research for

© 2009 by the National Kidney Foundation, Inc.0272-6386/09/5303-0102$36.00/0

doi:10.1053/j.ajkd.2008.11.017

h), 2009: pp S11-S15 S11

ctsCosbcrtitomtete

cccvwtrptmatwa

tLKaDtd

Ra

1

1

1

R

2

2

2

Executive SummaryS12

linicians and scientists to undertake in the fu-ure. Areas of uncertainty arose for several rea-ons. For some issues, research in the pediatricKD population has never been undertaken. Forthers, studies have provided indeterminate re-ults, either because of small sample size orecause infants, children, and adolescents wereonsidered together, precluding the ability toelate outcomes to specific age groups. Studieshat are rigorously designed to consider thesessues and more and that address such topics ashe role of inflammation on the nutritional statusf children, the contribution of nutrition manage-ent to modification of cardiovascular risk, and

he impact of frequent hemodialysis (HD) onnergy, protein, and vitamin needs are requiredo ensure that future recommendations are trulyvidence based.

The charge to the Work Group was to developomprehensive guideline recommendations thatould provide valuable assistance to all clini-ians (eg, dietitians, physicians, and nurses) in-olved in the nutritional management of childrenith CKD. We believe we have accomplished

hat goal. Of course, the primary use of theseecommendations is to complement—but not re-lace—clinical judgment and to recognize thathis is a “living document” that requires regularodification as new information becomes avail-

ble. When used in this manner, we are confidenthat the information contained in this documentill contribute to improved clinical management

nd outcomes of children with CKD.Finally, the Work Group expresses its apprecia-

ion to Michael Cheung, Dekeya Slaughter-arkem, and Donna Fingerhut of the NKF-DOQI Management Team and to Katrin Uhlig

nd Ethan Balk at the Tufts Center for Kidneyisease Guideline Development and Implemen-

ation for their guidance and assistance in theevelopment of this guideline.

RECOMMENDATIONS

ecommendation1: EvaluationofGrowthndNutritional Status

.1 The nutritional status and growth of allchildren with CKD stages 2 to 5 and 5Dshould be evaluated on a periodic basis.

(A)

.2 The following parameters of nutritionalstatus and growth should be considered incombination for evaluation in childrenwith CKD stages 2 to 5 and 5D. (B)

i Dietary intake (3-day diet record orthree 24-hour dietary recalls)

ii Length- or height-for-age percentileor standard deviation score (SDS)

iii Length or height velocity-for-age per-centile or SDS

iv Estimated dry weight and weight-for-age percentile or SDS

v BMI-for-height-age percentile or SDSvi Head circumference-for-age percen-

tile or SDS (<3 years old only)vii Normalized protein catabolic rate

(nPCR) in hemodialyzed adolescentswith CKD stage 5D.

.3 It is suggested that the frequency of moni-toring nutritional and growth parametersin all children with CKD stages 2 to 5 and5D be based on the child’s age and stageof CKD (Table 1). (C) In general, it issuggested that assessments be performedat least twice as frequently as they wouldbe performed in a healthy child of thesame age. (C) Infants and children withpolyuria, evidence of growth delay, de-creasing or low BMI, comorbidities influ-encing growth or nutrient intake, or re-cent acute changes in medical status ordietary intake may warrant more fre-quent evaluation. (C)

ecommendation2: Growth

.1 Identification and treatment of existingnutritional deficiencies and metabolic ab-normalities should be aggressively pur-sued in children with CKD stages 2 to 5and 5D, short stature (height SDS <�1.88 or height-for-age < 3rd percentile),and potential for linear growth. (A)

.2 Serum bicarbonate level should be cor-rected to at least the lower limit of normal(22 mmol/L) in children with CKD stages2 to 5 and 5D. (B)

.3 Recombinant human growth hormone(rhGH) therapy should be considered inchildren with CKD stages 2 to 5 and 5D,

short stature (height SDS < �1.88 or

Ra

3

3

3

3

RT

4

4

4

4

4

4

RT

5

5

Executive Summary S13

height-for-age < 3rd percentile), andpotential for linear growth if growthfailure (height velocity-for-age SDS <�1.88 or height velocity-for-age < 3rdpercentile) persists beyond 3 monthsdespite treatment of nutritional deficien-cies and metabolic abnormalities. (B)

ecommendation3: NutritionalManagementndCounseling

.1 Nutrition counseling, based on an indi-vidualized assessment and plan of care,should be considered for children withCKD stages 2 to 5 and 5D and theircaregivers. (B)

.2 Nutritional intervention that is individual-ized according to results of the nutritionalassessment and with consideration of thechild’s age, development, food prefer-ences, cultural beliefs, and psychosocialstatus should be considered for childrenwith CKD stages 2 to 5 and 5D. (B)

.3 Frequent reevaluation and modificationof the nutrition plan of care is suggestedfor children with CKD stages 2 to 5 and5D. (C) More frequent review is indicatedfor infants and children with advancedstages of CKD, relevant comorbiditiesinfluencing growth or nutrient intake,evidence of inadequate intake or malnutri-tion, or if acute illness or adverse eventsoccur that may negatively impact on nutri-tional status. (C)

.4 Nutritional management, coordinated bya dietitian who ideally has expertise inpediatric and renal nutrition, is suggestedfor children with CKD stages 2 to 5 and5D. (C) It is suggested that nutritionalmanagement be a collaborative effort in-volving the child, caregiver, dietitian, andother members of the multidisciplinarypediatric nephrology team (ie, nurses,social workers, therapists, and nephrolo-gists). (C)

ecommendation4: EnergyRequirements andherapy

.1 Energy requirements for children withCKD stages 2 to 5 and 5D should be

considered to be 100% of the EER for

chronological age, individually adjustedfor PAL and body size (ie, BMI). (B)Further adjustment to energy intake issuggested based upon the response in rateof weight gain or loss. (B)

.2 Supplemental nutritional support shouldbe considered when the usual intake of achild with CKD stages 2 to 5 or 5D fails tomeet his or her energy requirements andthe child is not achieving expected rates ofweight gain and/or growth for age. (B)

.3 Oral intake of an energy-dense diet andcommercial nutritional supplementsshould be considered the preferred routefor supplemental nutritional support forchildren with CKD stages 2 to 5 and 5D.(B) When energy requirements cannot bemet with oral supplementation, tube feed-ing should be considered. (B)

.4 A trial of intradialytic parenteral nutri-tion (IDPN) to augment inadequate nutri-tional intake is suggested for malnour-ished children (BMI-for-height-age < 5thpercentile) receiving maintenance HD whoare unable to meet their nutritional re-quirements through oral and tube feed-ing. (C)

.5 A balance of calories from carbohydrateand unsaturated fats within the physiolog-ical ranges recommended as the AMDR ofthe DRI is suggested when prescribingoral, enteral, or parenteral energy supple-mentation to children with CKD stages 2to 5 and 5D. (C)

.6 Dietary and lifestyle changes are sug-gested to achieve weight control in over-weight or obese children with CKD stages2 to 5 and 5D. (C)

ecommendation5: ProteinRequirements andherapy

.1 It is suggested to maintain dietary pro-tein intake (DPI) at 100% to 140% ofthe DRI for ideal body weight in chil-dren with CKD stage 3 and at 100% to120% of the DRI in children with CKDstages 4 to 5. (C)

.2 In children with CKD stage 5D, it issuggested to maintain DPI at 100% of the

DRI for ideal body weight plus an allow-

5

RR

6

6

6

RR

7

7

7

RR

8

Executive SummaryS14

ance for dialytic protein and amino acidlosses. (C)

.3 The use of protein supplements to aug-ment inadequate oral and/or enteralprotein intake should be consideredwhen children with CKD stages 2 to 5and 5D are unable to meet their proteinrequirements through food and fluidsalone. (B)

ecommendation6: Vitamin andTrace Elementequirements andTherapy

.1 The provision of dietary intake consistingof at least 100% of the DRI for thiamin(B1), riboflavin (B2), niacin (B3), panto-thenic acid (B5), pyridoxine (B6), biotin(B8), cobalamin (B12), ascorbic acid (C),retinol (A), �-tocopherol (E), vitamin K,folic acid, copper, and zinc should beconsidered for children with CKD stages2 to 5 and 5D. (B)

.2 It is suggested that supplementation ofvitamins and trace elements be providedto children with CKD stages 2 to 5 ifdietary intake alone does not meet 100%of the DRI or if clinical evidence of adeficiency, possibly confirmed by lowblood levels of the vitamin or trace ele-ment, is present. (C)

.3 It is suggested that children with CKDstage 5D receive a water-soluble vitaminsupplement. (C)

ecommendation7: BoneMineral andVitaminDequirements andTherapy

.1: Calcium7.1.1 In children with CKD stages 2 to 5

and 5D, it is suggested that the totaloral and/or enteral calcium intakefrom nutritional sources and phos-phate binders be in the range of100% to 200% of the DRI forcalcium for age. (C)

.2: Vitamin D7.2.1 In children with CKD stages 2 to 5

and 5D, it is suggested that serum25-hydroxyvitamin D levels be mea-sured once per year. (C)

7.2.2 If the serum level of 25-hydroxyvi-

tamin D is less than 30 ng/mL (75

nmol/L), supplementation with vita-min D2 (ergocalciferol) or vitaminD3 (cholecalciferol) is suggested. (C)

7.2.3 In the repletion phase, it is suggestedthat serum levels of corrected totalcalcium and phosphorus be mea-sured at 1 month after initiation orchange in dose of vitamin D and atleast every 3 months thereafter. (C)

7.2.4 When patients are replete with vita-min D, it is suggested to supple-ment vitamin D continuously andto monitor serum levels of 25-hydroxyvitamin D yearly. (C)

.3: Phosphorus7.3.1 In children with CKD stages 3 to 5

and 5D, reducing dietary phospho-rus intake to 100% of the DRI forage is suggested when the serumparathyroid hormone (PTH) con-centration is above the target rangefor CKD stage and the serum phos-phorus concentration is within thenormal reference range for age. (C)

7.3.2 In children with CKD stages 3 to 5and 5D, reducing dietary phospho-rus intake to 80% of the DRI forage is suggested when the serumPTH level is above the target rangefor CKD stage and the serum phos-phorus concentration exceeds thenormal reference range for age. (C)

7.3.3 After initiation of dietary phospho-rus restriction, it is suggested thatserum phosphorus concentration bemonitored at least every 3 monthsin children with CKD stages 3 to 4and monthly in children with CKDstage 5 and 5D. (C) In all CKDstages, it is suggested to avoid se-rum phosphorus concentrationsboth above and below the normalreference range for age. (C)

ecommendation8: Fluid andElectrolyteequirements andTherapy

.1 Supplemental free water and sodium supple-ments should be considered for children

with CKD stages 2 to 5 and 5D and polyuria

8

8

8

8

R

9

Ro

1

1

1

1

1

1

1

Executive Summary S15

to avoid chronic intravascular depletionand to promote optimal growth. (B)

.2 Sodium supplements should be consid-ered for all infants with CKD stage 5D onperitoneal dialysis (PD) therapy. (B)

.3 Restriction of sodium intake should be con-sidered for children with CKD stages 2 to 5and 5D who have hypertension (systolicand/or diastolic blood pressure > 95th per-centile) or prehypertension (systolic and/ordiastolic blood pressure > 90th percentileand < 95th percentile). (B)

.4 Fluid intake should be restricted in chil-dren with CKD stages 3 to 5 and 5D whoare oligoanuric to prevent the complica-tions of fluid overload. (A)

.5 Potassium intake should be limited for chil-dren with CKD stages 2 to 5 and 5D whohave or are at risk of hyperkalemia. (A)

ecommendation9: Carnitine

.1 In the opinion of the Work Group, there iscurrently insufficient evidence to suggesta role for carnitine therapy in childrenwith CKD stage 5D.

ecommendation10: NutritionalManagementf Transplant Patients

0.1 Dietary assessment, diet modifications,and counseling are suggested for chil-dren with CKD stages 1 to 5T to meetnutritional requirements while minimiz-ing the side effects of immunosuppres-sive medications. (C)

0.2 To manage posttransplantation weightgain, it is suggested that energy require-ments of children with CKD stages 1 to5T be considered equal to 100% of theEER for chronological age, adjusted for

PAL and body size (ie, BMI). (C) Further

adjustment to energy intake is suggestedbased upon the response in rate of weightgain or loss. (C)

0.3 A balance of calories from carbohydrate,protein, and unsaturated fats within thephysiological ranges recommended bythe AMDR of the DRI is suggested forchildren with CKD stages 1 to 5T toprevent or manage obesity, dyslipide-mia, and corticosteroid-induced diabe-tes. (C)

0.4 For children with CKD stages 1 to 5Tand hypertension or abnormal serummineral or electrolyte concentrations as-sociated with immunosuppressive drugtherapy or impaired kidney function,dietary modification is suggested. (C)

0.5 Calcium and vitamin D intakes of atleast 100% of the DRI are suggested forchildren with CKD stages 1 to 5T. (C) Inchildren with CKD stages 1 to 5T, it issuggested that total oral and/or enteralcalcium intake from nutritional sourcesand phosphate binders not exceed 200%of the DRI (see Recommendation 7.1).(C)

0.6 Water and drinks low in simple sugarsare the suggested beverages for chil-dren with CKD stages 1 to 5T with highminimum total daily fluid intakes (ex-cept those who are underweight, ie,BMI-for-height-age < 5th percentile)to avoid excessive weight gain, pro-mote dental health, and avoid exacer-bating hyperglycemia. (C)

0.7 Attention to food hygiene/safety andavoidance of foods that carry a high riskof food poisoning or food-borne infectionare suggested for immunosuppressed

children with CKD stages 1 to 5T. (C)

gaiscbccttss

1

1

DH

H

E

B

H

n

S

RECOMMENDATION 1: EVALUATION OF GROWTH

AND NUTRITIONAL STATUS

1

INTRODUCTIONNormal growth and development are major

oals of pediatric CKD management. Becausedequate nutritional status is important in achiev-ng these goals, careful monitoring of nutritionaltatus is essential. Nutritional status is a complexoncept that cannot be adequately summarizedy a single measurement. Multiple measures,onsidered collectively, are required to give aomplete and accurate picture of nutritional sta-us. Growth parameters are particularly impor-ant in children and should be accurately mea-ured using calibrated equipment andtandardized techniques (see Appendix 1).

.1 The nutritional status and growth ofall children with CKD stages 2 to 5 and5D should be evaluated on a periodicbasis. (A)

.2 The following parameters of nutritionalstatus and growth should be considered incombination for evaluation in childrenwith CKD stages 2 to 5 and 5D. (B)

i Dietary intake (3-day diet record orthree 24-hour dietary recalls)

Table 1. Recommended Parameters and Fwith CKD Sta

Measure

Age 0 to �1 y

CKD 2-3 CKD 4-5 CKD 5D C

ietary intake 0.5-3 0.5-3 0.5-2eight or length-for-agepercentile or SDS 0.5-1.5 0.5-1.5 0.5-1eight or lengthvelocity-for-agepercentile or SDS 0.5-2 0.5-2 0.5-1

stimated dry weightand weight-for-agepercentile or SDS 0.5-1.5 0.5-1.5 0.25-1

MI-for-height-agepercentile or SDS 0.5-1.5 0.5-1.5 0.5-1ead circumference-for-age percentile or SDS 0.5-1.5 0.5-1.5 0.5-1

PCR N/A N/A N/A

Abbreviation: N/A, not applicable.

*Only applies to adolescents receiving HD.

American Journal of Kidney D16

ii Length- or height-for-age percentileor standard deviation score (SDS)

iii Length or height velocity-for-age per-centile or SDS

iv Estimated dry weight and weight-for-age percentile or SDS

v BMI-for-height-age percentile or SDSvi Head circumference-for-age percen-

tile or SDS (<3 years old only)vii Normalized protein catabolic rate

(nPCR) in hemodialyzed adolescentswith CKD stage 5D.

.3 It is suggested that the frequency of moni-toring nutritional and growth parametersin all children with CKD stages 2 to 5 and5D be based on the child’s age and stageof CKD (Table 1). (C) In general, it issuggested that assessments be performedat least twice as frequently as they wouldbe performed in a healthy child of thesame age. (C) Infants and children withpolyuria, evidence of growth delay, de-creasing or low BMI, comorbidities influ-encing growth or nutrient intake, or re-

cy of Nutritional Assessment for Childrento 5 and 5D

Minimum Interval (mo)

Age 1-3 y Age �3 y

CKD 4-5 CKD 5D CKD 2 CKD 3 CKD 4-5 CKD 5D

1-3 1-3 6-12 6 3-4 3-4

1-2 1 3-6 3-6 1-3 1-3

1-3 1-2 6 6 6 6

1-2 0.5-1 3-6 3-6 1-3 1-3

1-2 1 3-6 3-6 1-3 1-3

1-2 1-2 N/A N/A N/A N/AN/A N/A N/A N/A N/A 1*

requenges 2

KD 2-3

1-3

1-3

1-6

1-3

1-3

1-3N/A

iseases, Vol 53, No 3, Suppl 2 (March), 2009: pp S16-S26

cb

sbs

racagdiwEidptpsdp(aoCdufHcrnfmtacah

i

asapomcsga

tbcr3dctigimhpndtwushlcltbCtl

aeoi

ci

Evaluation of Growth and Nutritional Status S17

cent acute changes in medical status ordietary intake may warrant more fre-quent evaluation. (C)

RATIONALE

1.1: The nutritional status and growth of allhildren with CKD stages 2 to 5 and 5D shoulde evaluated on a periodic basis. (A)1.2: The following parameters of nutritional

tatus and growth should be considered in com-ination for evaluation in children with CKDtages 2 to 5 and 5D. (B)

Because of the high prevalence of growthetardation in children with CKD, nutrition haslways been a primary focus of pediatric CKDare. Early studies emphasized the importance ofdequate energy intake in maintaining normalrowth in pediatric CKD. However, no studyemonstrated a growth advantage to a caloricntake greater than about 75% of the RDA,2-4

hich corresponds approximately to 100% of theER in children older than 3 months. Interest-

ngly, the prevalence of undernutrition in chil-ren with CKD is unknown. This is likely due, inart, to an inadequate definition of undernutri-ion in this population. In children with CKD, therevalence of undernutrition has been demon-trated to vary widely—from 2% to 65%—epending on the definition used.5 In the generalopulation, the World Health OrganizationWHO) has defined undernutrition as weight-for-ge, height-for-age, and weight-for-height 2 SDsr greater less than the Centers for Diseaseontrol and Prevention (CDC) reference me-ian,6 in recognition of the fact that long-termndernutrition may lead to wasting (low weight-or-height) and/or stunting (low height-for-age).owever, this definition may be inappropriate in

hildren with CKD. Whereas stunting can beeasonably attributed solely to long-term under-utrition in otherwise healthy children, the multi-actorial cause of stunting in children with CKDakes it a poor choice as a definition of undernu-

rition in this group. In the CKD population,nthropometric definitions of undernutrition areomplicated; consideration must be given to theppropriateness of measures for both age andeight of the child.Body composition has yet to be well character-

zed in pediatric CKD. Few high-quality studies p

re available in which measures of body compo-ition were adequately adjusted for height andppropriately compared with a healthy referenceopulation.7-12 Of these, lean mass deficits werebserved in some studies,11 but not others.7 Fatass appears to be increased relative to height in

hildren with CKD.11 Preliminary evidence inmall numbers of children suggests that use ofrowth hormone may result in lower fat massnd higher lean mass for height.11

Interpretation of many prior studies of nutri-ion and growth in pediatric CKD is difficultecause most studies considered infants and olderhildren together as a uniform group. There areeasons to believe that infants younger than 2 toyears behave very differently from older chil-

ren. At a theoretical level, there are 2 mainonsiderations. First, a much larger proportion ofhe daily energy requirement is devoted to growthn infants compared with older children. Second,rowth is driven primarily by nutrition duringnfancy, whereas growth hormone and sex hor-ones have a dominant influence during child-

ood and adolescence, respectively.13-16 On aractical level, there is evidence to support theotion that infants and older children behaveifferently. Inadequate spontaneous calorie in-ake has been clearly demonstrated in infantsith CKD17-19; energy intakes for older childrensually are normal relative to body size.9 Intudies separating children by age, weight-for-eight indices, and BMI-for-age, z scores wereow in younger children, but normal in olderhildren.10,12 Lean mass deficits were also moreikely in younger than older children.7,8,10 Rou-ine calorie and/or protein supplementation haveeen shown to improve growth in infants withKD.17-19 However, there is no clear evidence

hat routine nutritional supplements have a simi-ar effect in older children.

Because of these differences between infantsnd older children, the present recommendationsmphasize the importance of considering the agef the child when planning nutritional monitor-ng and interventions.

Historically, the main focus of malnutrition inhildren with CKD has been undernutrition; theres some evidence that obesity is beginning to be a

roblem in the CKD population.20-22

D

rmciqmd3dotelgmecstadctImt3Dvdpdtdasr

atincppcor

L

dpaliCkg(bsr1hytaaalggmpclCidpgg

autCopdAcId(di

Recommendation 1S18

ietary Intake

It is suggested that dietary intake be assessedegularly by a skilled registered dietitian byeans of a 3-day diet diary. Three 24-hour re-

alls may be preferable in adolescents. Dietaryntake data provide useful information about theuantity and quality of nutrients ingested. The 2ost practical and clinically feasible ways to

etermine usual daily intake are the prospective-day dietary diary and the retrospective 24-hourietary recall. From either of these, daily intakef calories, macronutrients (carbohydrate, pro-ein, and fat), vitamins, and minerals can bestimated. Each of the methods has its ownimitations. Dietary diaries have been shown toive unbiased estimates of energy intake in nor-al-weight children younger than 10 years; how-

ver, underreporting is common in adoles-ents.23,24 Twenty-four–hour recalls may be betteruited to adolescents. The most important limita-ion of the 24-hour recall method is its poorbility to capture the day-to-day variability inietary intake. Children may be even more sus-eptible to this limitation than adults becausehey tend to have more day-to-day variability.25

t may be useful to obtain three 24-hour recalls toore completely evaluate the food-intake pat-

ern. One weekend day should be included in a-day diet diary and as 1 of three 24-hour recalls.espite their limitations, dietary recall inter-iews conducted by a skilled pediatric registeredietitian or dietary diaries completed by theatient and/or parent as instructed by a registeredietitian provide useful general information abouthe pattern of food intake. Information aboutietary intake allows the treating team to evalu-te the adequacy of a patient’s intake beforeignificant adverse changes in body compositionesult.

Poor intake is expected in infants with CKDnd should prompt immediate initiation of nutri-ional supplements if there is any evidence ofnadequate weight gain or growth. When sponta-eous intake is low in a poorly growing olderhild, consideration also must be given to theossibility that the poor intake is a result of theoor growth, rather than the cause. Spontaneousalorie intake increased by almost 12% in a studyf 33 children with CKD during treatment with

hGH.26 t

ength- orHeight-for-AgePercentile or SDS

Length (infants � 2 years) or height (chil-ren � 2 years) should be measured regularly,lotted on the length- or height-for-age curves,nd the percentile and/or SDS should be calcu-ated (Appendix 2, Table 32). Growth retardations common in CKD.2,3,12,27,28 The impact ofKD on growth depends on both the degree ofidney impairment and age of the child. Normalrowth can be divided into 3 phases: infancydominated by nutrition), childhood (dominatedy growth hormone), and puberty (dominated byex hormones).13 The infancy phase normally iseplaced by the childhood pattern between 6 and2 months of age. In CKD, onset of the child-ood phase frequently is delayed until 2 to 3ears of age or interrupted by a transient resump-ion of the infancy pattern.13 CKD also results indelay in the onset of pubertal growth, as well asshorter pubertal growth spurt.29 Together, theselterations to the normal pattern of growth mayead to severe short stature. The typical CKDrowth pattern is characterized by decreasedrowth velocity during infancy, followed by nor-al growth velocity during childhood and im-

aired growth velocity again during adoles-ence.16 However, growth velocity also may beow during the childhood phase in children withKD stages 4 or 5.3,30 Numerous factors may

nfluence growth in CKD, including acidosis,31

isturbances in the growth hormone axis,32 andoor nutritional intake.2 Nutritional intake has itsreatest influence during the infancy phase ofrowth.16

Length (infants) should be measured by usinglength board, and height (older children), by

sing a wall-mounted stadiometer, preferably byhe same well-trained person at each assessment.alculating the SDS or plotting the child’s heightn the normal growth chart to determine theercentile allows comparison with healthy chil-ren. In 2000, the CDC published revised Northmerican growth reference charts for infants and

hildren up to 20 years of age (Figs 11 to 14).33

n 2006, the WHO released new growth stan-ards for children from birth to 5 years of ageFigs 1 to 10).34 These growth standards areistinguished from the CDC reference charts in 2mportant ways. First, the children contributing

o the WHO Growth Standards were specifically

siwaibdppNtirewt

sgSctGtlattdt

pohccsao

●

●

coch

arma

eailuusa

LS

ohywcmgddHcuSvvymg

EP

lfsoie“inll

Evaluation of Growth and Nutritional Status S19

elected to represent children growing underdeal conditions: they had nonsmoking mothers,ere from areas of high socioeconomic status,

nd received regular pediatric health care, includ-ng immunizations. A subset of 882 infants, allreastfed for at least 4 months, provided longitu-inal data for 24 months. Second, the studyopulation was of broad ethnic diversity; partici-ants were recruited from Brazil, Ghana, India,orway, Oman, and the United States. Impor-

antly, ethnicity had very little impact on growth,ndicating that the growth standards reflect aeasonable expectation for growth regardless ofthnicity; only 3% of the variability in growthithin the population could be attributed to coun-

ry of origin.34

Because the WHO Growth Standards repre-ent ideal growth and ideal growth should be theoal for children with CKD, the WHO Growthtandards should be used as the reference forhildren from birth to 2 years. Differences be-ween the CDC reference curves and the WHOrowth Standards are minimal after 2 years. For

his reason and because the switch is made fromength to height measurement at 2 years, 2 yearsppears to be a reasonable age to make theransition from the WHO Growth Standards tohe CDC reference curves (www.rcpch.ac.uk/oc.aspx?id_Resource�2862; last accessed Oc-ober 23, 2008).

It may be useful to consider the genetic heightotential of the child when assessing adequacyf growth. Although the exact contribution oferedity cannot be calculated, an estimate of ahild’s adult height potential can be made byalculating midparental height adjusted for theex of the child. Midparental height is calculateds follows (see Appendix 2, Table 33 for annline calculator):

Girls: 5 inches (13 cm) is subtracted from thefather’s height and averaged with the mother’sheight;Boys: 5 inches (13 cm) is added to themother’s height and averaged with the father’sheight.

The midparental height is plotted on the growthhart (of the same gender as the child) at 20 yearsf age. For both girls and boys, 3.5 inches (8.5m) on either side of this calculated value (target

eight) represents the 3rd to 97th percentiles for a

nticipated adult height.35 The 5 inches (13 cm)epresents the average difference in height ofen and women; thus, the child grows, on aver-

ge, to the midparental height percentile.Adequate growth is a good indication of ad-

quate nutrition over the long term. However,cute weight loss may be severe and alterationsn body composition may be substantial beforeinear growth is impaired. Growth usually contin-es at a normal rate in malnourished childrenntil significant wasting occurs.36 For this rea-on, additional measures of nutritional status aredvised.

engthorHeightVelocity-for-AgePercentile orDS

The growth velocity (change in height per unitf time) can be determined by recording serialeight measurements. In children younger than 2ears, the change in length percentile and/or SDSill give an idea of growth velocity (a negative

hange indicates poor growth; a positive changeay represent catch-up growth). Calculation of

rowth velocity percentile and/or SDS for chil-ren younger than 2 years can be done by usingata from the 2006 WHO Growth Standards.eight velocity percentile and/or SDS can be

alculated for children older than 2 years bysing reference data from the Fels Longitudinaltudy.37 It is important to recognize that heightelocity cannot be accurately assessed for inter-als shorter than 6 months in those older than 2ears. However, more frequent height measure-ents allow a running look at growth and give a

eneral impression of its adequacy.

stimatedDryWeight andWeight-for-Ageercentile or SDS

Euvolemic weight should be determined regu-arly. The weight should be plotted on the weight-or-age curves, and the percentile and/or SDShould be calculated. Weight is an important partf any nutritional assessment. In CKD, it ismportant to ensure that weight is measured in auvolemic state. This generally is referred to asdry weight” because fluid overload is commonn those with CKD stage 5. Children with chronicephrotic syndrome also may have fluid over-oad, even at milder stages of CKD. Fluid over-oad will influence not just weight, but also may

ffect other anthropometric measures, such as

aVcoecwwFpsvctra(udpwvodOcaseaoaw

sm(nGegtwiri

B

tb

almHviepmmspbisccwaaacndhnmuwaewhacg

satmoctoBtcra

Recommendation 1S20

rm circumference and skinfold thicknesses.38,39

olume depletion also may be present in someonditions resulting in pediatric CKD (dysplasia,bstructive nephropathy, and cystinosis). It isqually important that the euvolemic weight beonsidered in these cases. The estimated dryeight can be challenging to ascertain becauseeight gain is expected in growing children.ive parameters are helpful in the estimationrocess: weight, presence of edema, blood pres-ure, certain laboratory values, and dietary inter-iew. The midweek postdialysis weight and theombination of noninvasive blood volume moni-oring and the postdialytic vascular compartmentefilling rate are used for evaluation purposes inn HD patient.40 The weight at a monthly visitminus dialysis fluid in the peritoneal cavity) issed for the child on PD therapy. The estimatedry weight is challenging to evaluate in patientsrone to edema and must be done in conjunctionith a physical examination. Excess fluid may beisible in the periorbital, pedal, and other regionsf the body. Hypertension that resolves withialysis can be indicative of excess fluid weight.ther responses to dialytic fluid removal, such as

ramping or hypotension, may also give cluesbout the fluid status of the patient. Decreasederum sodium and albumin levels may be mark-rs of overhydration. Rapid weight gain in thebsence of a significant increase in energy intaker decrease in physical activity must be evalu-ted critically before it is assumed to be dryeight gain.After the dry weight has been determined, it

hould be used to calculate the BMI and deter-ine the weight-for-age percentile and/or SDS

or be plotted on the weight-for-age curves). Asoted in the section on height, the 2006 WHOrowth Standards should be used as the refer-

nce for children up to 2 years; the 2000 CDCrowth charts should be used for children olderhan 2 years. It is important to recognize that theeight-for-age SDS is not particularly useful in

solation—weight-for-age will be low in growth-etarded children. Rather, it should be interpretedn the context of the height-for-age SDS.

MI-for-Height-AgePercentile or SDS

It is suggested that BMI be determined eachime height and weight are measured. BMI should

e plotted on the sex-specific BMI-for-age curves, c

nd the percentile and/or SDS should be calcu-ated. BMI is an accepted and easily calculatedethod of evaluating weight relative to height.owever, BMI, calculated as weight (kg) di-ided by height (m) squared is not completelyndependent of either age or height. This isxplained in part by age-related changes in bodyroportions and in part by mathematics: a 1-di-ensional measure (height) will predict a 3-di-ensional measure (increasing weight repre-

ents body growth in 3 dimensions) to the thirdower, not the second power.41 The solution haseen to express BMI relative to age in develop-ng children.42 In this relation, age functions as aurrogate for both height and maturation. Be-ause height, age, and maturation are highlyorrelated in healthy children, this approachorks reasonably well. Sex-specific BMI-for-

ge reference data permit calculation of BMI-for-ge z scores or percentiles, allowing meaningfulnd consistent interpretation of BMI in normalhildren regardless of age. In children with kid-ey disease, in whom growth retardation andelayed maturation are common, this approachas limitations. Expressing BMI relative to chro-ological age in a child with growth and/oraturational delay will result in inappropriate

nderestimation of his or her BMI comparedith peers of similar height and developmental

ge. To avoid this problem, it may preferable toxpress BMI relative to height-age in childrenith CKD—that is, the age at which the child’seight would be on the 50th percentile.38,523 Thispproach ensures that children with CKD areompared with the most appropriate referenceroup: those of similar height and maturation.Height-age is believed to provide a reasonable

urrogate for maturation in most children (ie, thege at which a child would be at the 50th percen-ile for height likely is close to the age at whichost healthy children would have a similar level

f sexual/physical development). Similarly, inhildren with short stature, expressing BMI rela-ive to height-age will minimize errors that mayccur as a result of the correlation betweenMI-for-age and height-for-age. However, cau-

ion must be used in applying this approach tohildren outside the pubertal or peripubertal pe-iod, for whom the correlation between height-ge and maturation is less clear. BMI relative to

hronological age may be more logical in some

cc

iBobrnemtrh

anm1taWwatdTs(scptttsirtrcsmgBwdmgme

aIdmsaw

CaFw0atB

thidaABBaSdiiTCBhtara

H

lcciwhnom

Evaluation of Growth and Nutritional Status S21

ases, particularly when sexual maturation isomplete.

Although the weight-for-height index is a mean-ngful measure during early and midchildhood,MI has the advantage of being applicable through-ut the lifespan, from infancy to adulthood, and isecoming the standard method of assessing weightelative to height.43 While BMI-for-age charts areow available from birth onwards, clinical experi-nce in using and interpreting BMI before 24onths of age is limited, as are data on its associa-

ion with current or future morbidity and for thiseason, BMI is suggested rather than weight-for-eight index after the age of 2 years.

The CDC defines underweight as a BMI-for-ge less than the 5th percentile (www.cdc.gov/ccdphp/dnpa/growthcharts/training/modules/odule1/text/page5a.htm; last accessed February

, 2008).44 A BMI-for-age greater than or equalo the 85th percentile is considered overweight,nd greater than the 95th percentile, obese.45 TheHO definitions of underweight differ some-hat from those used by the CDC. A BMI-for-

ge SDS of �2.0 (BMI-for-age � � 3rd percen-ile) recently has been proposed as a cutoff toefine underweight or “thinness” in children.his definition is attractive because it corre-ponds to the cutoff for grade 2 thinness in adultsBMI, 17 kg/m2).43 However, no high-qualitytudies are available linking BMI less than aertain cutoff to poor outcomes in the generalopulation. Therefore, no evidence-based defini-ions of undernutrition or “thinness” exist. Fur-hermore, the applicability of such definitions tohe CKD population is unknown. Two largetudies of adult HD patients demonstrated annverse relationship between BMI and mortalityisk, with no clear BMI threshold above whichhe risk stabilized or began to increase; mortalityisk continued to decrease even as BMI in-reased to greater than 30 kg/m2.46,47 A smallertudy of adult HD patients suggested increasedortality risk with BMI less than 17 and BMI

reater than 23 kg/m2 compared with those withMI between 17.0 and 18.9 kg/m2.48 In childrenith stage 5 CKD, a U-shaped association wasemonstrated between BMI-for-age SDS andortality risk. Children with a BMI SDS either

reater or less than 0.50 had a greater risk ofortality than those with a BMI SDS of 0.5;

ach 1.0-SD unit difference in BMI SDS was t

ssociated with a 6% greater risk of mortality.49

t is important to recognize that this study onlyemonstrated an association between BMI andortality, but could not establish a causal relation-

hip. Furthermore, the additional mortality riskssociated with BMI SDS greater or less than 0.5as small.Interpretability of BMI may be limited in the

KD population due to fluid overload. Clearly,ny excess fluid will artificially increase BMI.luid overload representing 10% of the bodyeight will result in a BMI SDS approximately.5 to 1.0 SD units greater than what it would bet dry weight. Therefore, efforts should be madeo use only a true dry weight when calculatingMI.High-quality reference values for BMI rela-

ive to age are now available throughout child-ood. The 2000 CDC revised growth chartsnclude sex-specific BMI-for-age curves for chil-ren and adolescents between 2 and 20 years ofge.33 These curves, developed using a Northmerican population, provide a contemporaryMI reference that recognizes the dependence ofMI on age and allow calculation of BMI-for-ge SDS and percentiles. The 2006 WHO Growthtandards also include BMI standards for chil-ren from birth to 5 years of age (www.who.nt/childgrowth/standards/technical_report/en/ndex.html; last accessed October 23, 2008).34

ogether, the WHO Growth Standards and theDC growth charts provide reference values forMI from birth to adulthood. As for length andeight measures, BMI should be compared withhe WHO Growth Standards up to 2 years of agend with the CDC growth charts thereafter (www.cpch.ac.uk/doc.aspx?id_Resource�2862; lastccessed October 23, 2008).

eadCircumference-for-AgePercentile or SDS

Head circumference should be measured regu-arly in children 3 years and younger. Headircumference should be plotted on the headircumference-for-age curves. Poor head growths well documented in children with CKD,50,51

ith infants at highest risk. Although no studiesave specifically related head circumference toutritional status in CKD, regular measurementsf head circumference in conjunction with inter-ittent developmental assessments are an impor-

ant part of routine pediatric CKD care. The 2007

Wr

N

ai

ariwpnulbunmtaril

wptawidi

fi

w(

pttnsds

qd

lslwcaltwpnmtdfpbro

opttttoKmHtl

itsp(uw(aAarMs

Recommendation 1S22

HO Growth Standards should be used as aeference.52

ormalizedProteinCatabolic Rate

PEM may have profound effects on growthnd development and may be associated withncreased risk of morbidity and mortality.

Protein catabolic rate (PCR) has been studieds an objective measure of DPI in stable patientseceiving maintenance HD. PCR can be normal-zed to a patient’s weight (nPCR); nPCR initiallyas studied in the 1980s as a marker of DPI inediatric HD patients assumed to be in stableitrogen balance.53 Calculation of nPCR is basedpon the increase in blood urea nitrogen (BUN)evel from the end of 1 HD treatment to theeginning of the next treatment to calculate therea generation rate (G; mg/min). nPCR origi-ally was calculated by using formal urea kineticodeling in association with Kt/V calcula-

ions.54 Recent pediatric data demonstrate thatlgebraic formulas yield nearly identical nPCResults compared with formal urea kinetic model-ng.55 The algebraic nPCR calculation is as fol-ows:

G (mg ⁄ min) � [(C2 � V2) � (C1 � V1)] ⁄ t

here C1 is postdialysis BUN (mg/dL), C2 isredialysis BUN (mg/dL), V1 is postdialysisotal-body water (dL; V1 � 5.8 dL/kg � postdi-lysis weight in kg), V2 is predialysis total-bodyater (dL; V2 � 5.8 dL/kg � predialysis weight

n kg), and t is time (minutes) from the end of theialysis treatment to the beginning of the follow-ng treatment.

Then, nPCR is calculated by using the modi-ed Borah equation56:

nPCR � 5.43 � estG ⁄ V1 � 0.17

here V1 is total-body water (L) postdialysis0.58 � weight in kg).

Data from adult studies demonstrate that there- and postdialysis BUN levels from the samereatment can be used to calculate nPCR; addi-ional blood sampling from the next treatment isot necessary.57 Recent pediatric data demon-trated increases in nPCR in malnourished chil-ren on HD therapy who received IDPN. In these

tudies, higher nPCR was associated with subse- u

uent weight gain, whereas lower nPCR pre-icted future weight loss in adolescents.58,59

Comparison of nPCR versus serum albuminevel in an entire single-center population, irre-pective of nutrition status, showed that nPCRess than 1 g/kg/d of protein predicted a sustainedeight loss of at least 2% per month for 3

onsecutive months in adolescent and youngdult–aged patients,60 whereas serum albuminevels could not. In younger pediatric HD pa-ients, neither nPCR nor serum albumin levelas effective in predicting weight loss. Thisotentially could be explained by: (1) betterutritional status in infants and toddlers who areore likely to be tube fed, (2) a greater contribu-

ion of unmeasured urine urea clearance, (3)ifferences in protein catabolism, and/or (4) dif-erent growth rates in younger children com-ared with older children. It is also possible thatecause nPCR was derived in adult patientseceiving HD, nPCR may be a valid measurenly for patients of adult age or size.Although no data exist to guide recommended

ptimal nPCR measurement frequency in HDatients, the same data needed for Kt/V calcula-ion allow for nPCR calculation without addi-ional blood sampling. Thus, nPCR can be moni-ored monthly along with Kt/V to follow uprends for a particular patient and provide anbjective measure of protein intake.61 The/DOQI Adult Nutrition Guidelines recommendonthly assessment of nPCR for maintenanceD patients.62 It is suggested that nPCR level be

argeted to the age-specific protein intake guide-ines noted in Recommendation 5.

In a manner similar to the evaluation of nPCRn patients receiving HD, it is recommended thathe DPI of adults receiving PD be estimatedeveral times per year by determination of therotein equivalent of nitrogen appearancePNA).63 This is calculated by measuring therea nitrogen content of urine and dialysate,hich represents the total nitrogen appearance

TNA), and multiplying that value by 6.25 (therere �6.25 g of protein per 1 g of nitrogen).64

lthough limited data for this subject are avail-ble in pediatrics and the assessment is notegularly carried out in pediatric dialysis centers,

endley and Majkowski65 defined the relation-hip between urea nitrogen and TNA in children

ndergoing PD as follows:

T

c

iapi

T

wvtstmr

O

maitiBruttrCsomcptwmpot

(oaeTmmrlmt

mftepmnTt

aetoApiatfltbMdvs

bCpcdmCsne

Evaluation of Growth and Nutritional Status S23

NA (g ⁄ d) � 1.03 (urea nitrogen appearance)� 0.02 (weight in kg) � 0.56(for subjects age 0 to 5 years)or 0.98 (for subjects age 6 to 15 years)

Patient age was taken into consideration be-ause of its relationship to dialysate protein loss.

Edefonti et al66 later reported that incorporat-ng dialysate protein nitrogen and body surfacerea (BSA) in the formula could improve therediction of TNA. Their recommended formulas as follows:

NA (g ⁄ d) � 0.03 � 1.138 urea-Nurine

� 0.99 urea-Ndialysate � 1.18 BSA� 0.965 protein-Ndialysate

Limitations of PNA are that it is valid onlyhen the patient is not anabolic or catabolic, thealue changes rapidly when DPI is altered andhus may not reflect usual protein intake, and ithould be normalized for patient size, althoughhe best parameter to use has not been deter-ined. In adults, normalization to ideal weight is

ecommended.

therMeasures Considered

Serum albumin: Serum albumin was recom-ended in the 2000 K/DOQI Nutrition Guidelines

s a marker of nutritional status. Hypoalbuminemias a common finding in those with CKD and consis-ently has been associated with increased mortalityn both adults46,67-69 and children with CKD.70

ecause PEM may lead to hypoalbuminemia, se-um albumin level generally has been considered aseful index of nutritional status. However, impor-ant limitations have been identified with respect tohe ability of serum albumin level to function as aeliable marker of malnutrition in the setting ofKD.38,71-77 Serum albumin is depressed in the

etting of both systemic inflammation and volume-verload states.73,74 In the absence of inflammatoryarkers, hypoalbuminemia is not predictive of in-

reased mortality.77 Given the association of hy-oalbuminemia with mortality, it remains an impor-ant component of the general evaluation of patientsith CKD. However, the value of albumin as aarker of nutritional status is questionable. Hy-

oalbuminemia should lead to careful assessmentf volume status and protein loss and to investiga-

ion for causes of systemic inflammation. o

Mid-armanthropometry: Mid-arm circumferenceMAC) and triceps skinfold thickness (TSF) previ-usly were recommended as part of the nutritionalssessment in pediatric CKD.62 TSF was consid-red to reflect total fat mass, and the combination ofSF and MAC were used to calculate the mid-armuscle circumference (MAMC) and mid-armuscle area (MAMA), which are purported to

eflect total muscle mass. These measures are noonger recommended as a part of routine assess-ent. There are 4 main problems with the use of

hese measures.First, it is difficult to obtain reliable measure-ents, particularly in patients with CKD. Skin-

old thickness measurement is extremely opera-or dependent and lacks precision, except in veryxperienced hands.78 In children with CKD, theresence of fluid overload may result in overesti-ates and poor reliability of skinfold thick-

ess.38 MAC is easier to reliably measure thanSF, but is even more susceptible to overestima-

ion due to fluid overload.38,39

Second, it is not clear that MAMC and MAMAre accurate reflections of total muscle mass,ven in otherwise healthy individuals.38 The rela-ionship between total muscle mass and MAMCr MAMA is even less clear in those with CKD.bnormal regional distribution of lean tissue inatients with CKD79 may result in a breakdownn the relationship between MAMC or MAMAnd total muscle mass. Furthermore, the poten-ial errors associated with TSF and MAC due touid overload and distorted fat and lean distribu-

ion may be compounded when they are com-ined in equations to calculate MAMC andAMA. Arm measures failed to reliably detect

ecreased lean mass as measured by using inivo neutron activation analysis in at least 1tudy of adult HD patients.80

Third, deficits in these parameters have nevereen described convincingly in children withKD. Although arm measures have been re-orted to be low relative to age in prior studies ofhildren with CKD, there is little evidence thateficits exist when appropriate adjustments wereade for short stature. Given that children withKD are often short for age, proportionally

maller arm circumferences and skinfold thick-esses are expected. Arm measures would bexpressed more appropriately relative to height

r height-age. When this has been done, deficits

hTsyacthmaw5fyo5M

botma

bmigtutwwrcsisaaDj

ewbBafo

caaBamsb

ucBcmtsoovwcaB

tcummwcmatbw

wTflslbmsttawt

Recommendation 1S24

ave been rare. In only 1 pediatric study in whichSF was adjusted appropriately for height wereignificant deficits in TSF seen—and only inounger children.12 The mean TSF-for-height-ge z score was high at �0.9 in a study of 56hildren with CKD.5 There is growing evidencehat TSF and total fat mass are high relative toeight in the CKD population. Mean total fatass (determined by using dual-energy X-ray

bsorptiometry [DXA]) for height-age z scoreas �1.1 in 50 children with CKD stages 3 to.11 One study of PD patients found mean MAC-or-height-age z scores of �1.1 in 12 childrenounger than 10 years and �0.1 in 12 childrenlder than 10 years.12 However, another study of6 children with CKD stages 3 to 5 found a meanAC-for-height-age z score of �0.4.5

Finally, few studies have investigated the linketween TSF, MAC, MAMC, or MAMA andutcome in the CKD population. MAMC failedo be identified as an independent predictor ofortality in a 3-year longitudinal study of 128

dult HD patients.68

Dual-energyX-rayabsorptiometry(DXA): A whole-ody DXA scan provides excellent estimates of fatass and lean mass.81 The main limitation of DXA

n patients with CKD is that it is unable to distin-uish normally hydrated from overhydrated leanissue; thus, it may overestimate lean mass in vol-me-overloaded subjects. DXA has been used ex-ensively for body-composition assessment in adultsith CKD and in several small studies of childrenith CKD.11,82-86 Although deficits in lean mass

elative to height-age have been demonstrated inhildren with CKD,11 there are insufficient data toupport a recommendation for regular DXA scansn children with CKD. The added value of a DXAcan over such a simple and inexpensive measures BMI has yet to be proved. Significant advantagesssociated with the extra information provided byXA would need to be clearly demonstrated to

ustify the expense.

Bioelectrical impedanceanalysis (BIA): BIA allowsstimation of body fluid compartment volumes,hich may then be used to make inferences aboutody composition.87 However, despite extensiveIA studies, investigators have been unsuccessfult developing broadly applicable BIA methods thatunction well on the individual level.88-93 Margins

f error are so large as to render results of dubious t

linical value. Abnormalities in volume status prob-bly are the biggest problem limiting the interpret-bility of BIA measures in children with CKD. AllIA measures, including impedance and phasengle,94-96 will change when either fluid status, fatass, or lean mass changes. However, it is impos-

ible to distinguish which change has occurredased on BIA measures.

Single-frequency whole-body BIA has beensed in an effort to predict total-body water inhildren receiving maintenance dialysis.93 TheIA-derived total-body water estimates wereompared with total-body water measured byeans of isotope dilution (gold standard). Al-

hough the group mean total-body water mea-ured by using bioimpedance was within 170 mLf that measured by using isotope dilution, limitsf agreement were wide (�17% of the truealue). This means that an individual subjectith a true total-body water volume of 30 L

ould be estimated to have a total-body volumes high as 35.1 L or as low as 24.9 L by usingIA.Multiple-frequency BIA (bioimpedance spec-

roscopy) allows direct estimation of both extra-ellular fluid (ECF) and intracellular fluid vol-mes,97 although estimates of ECF volumes areore accurate.98 A small study of children withild-to-moderate chronic renal insufficiency usedhole-body bioimpedance spectroscopy to suc-

essfully estimate ECF volume within 6% of thateasured by using isotope dilution.91 Bioimped-

nce spectroscopy is a promising technique, par-icularly for estimating ECF, but it has not yeteen adequately validated in children or adultsith CKD.Whole-body BIA has significant limitations

hen abnormalities in fluid distribution exist.he technique is insensitive to large changes inuid volume in the trunk and very sensitive tomall changes in the limbs.99 To avoid this prob-em, a segmental bioimpedance technique haseen developed in which each of 5 body seg-ents (2 arms, 2 legs, and trunk) are measured

eparately.99 In an effort to avoid overrepresenta-ion of the limbs and underrepresentation of therunk in the final total-volume calculation, imped-nce from each segment is given appropriateeight; this accounts for the different contribu-

ions of each segment to total resistance.99 This

echnique may be particularly useful in fluid-

ov

dAon

cieoms

cagtsctsoa

oruCToiicwamaArdtmb

F

mi

bIpwsulnmm

aa1ocatmuy

bampqreCgftge

alrtimompcoca

Evaluation of Growth and Nutritional Status S25

verloaded persons. However, it has not beenalidated in children.A final potential application of BIA is to help

etermine whether an individual is euvolemic.lthough promising techniques have been devel-ped in this regard,100,101 these methods haveot yet been tested in children.

Multiparameter nutritional assessment scales: Be-ause no single parameter has been found that willdentify all patients at nutritional risk, multiparam-ter indices of nutritional status have been devel-ped in attempts to improve accuracy. Multi-itemeasures may increase reliability, scope, and preci-

ion compared with 1 individual objective measure.One such index was developed specifically for

hildren on PD therapy.102,103 Anthropometricnd bioimpedance measures were combined toenerate a score; however, the means by whichhe parameters were combined to arrive at a finalcore has limited justification and many of theomponent measures are highly correlated. Fur-hermore, the score is heavily influenced byingle-frequency BIA measurements, which aref questionable value. The method does notppear practical for routine clinical practice.

Subjective Global Assessment (SGA), a methodf nutritional assessment using clinical judgmentather than objective measures, has been widelysed to assess nutritional status of adults withKD104 for both clinical and research purposes.he clinician performing SGA considers 5 featuresf a medical-nutrition history (weight loss, dietaryntake, gastrointestinal symptoms, functional capac-ty, and metabolic stress) and 4 features of a physi-al examination (subcutaneous fat loss, muscleasting, edema, and ascites) to assign the patient

n overall rating of well nourished, moderatelyalnourished, or severely malnourished without

dhering to any kind of rigid scoring system.105,106

n SGA specifically for the pediatric populationecently has been developed and validated in chil-ren undergoing major surgery.107 Applicability ofhis pediatric Subjective Global Nutrition Assess-ent (SGNA) in children with CKD is currently

eing studied.

requencyofAssessment

1.3: It is suggested that the frequency ofonitoring nutritional and growth parameters

n all children with CKD stages 2 to 5 and 5D be r

ased on the child’s age and stage of CKD. (C)n general, it is suggested that assessments beerformed at least twice as frequently as theyould be performed in a healthy child of the

ame age. (C) Infants and children with poly-ria, evidence of growth delay, decreasing or

ow BMI, comorbidities influencing growth orutrient intake, or recent acute changes inedical status or dietary intake may warrantore frequent evaluation. (C)The frequency with which a nutritional evalu-

tion should be conducted depends on both thege of the child and the severity of CKD (Table). Current recommendations for measurementf growth parameters in healthy infants andhildren vary slightly by country. In general, 2ssessments are recommended in the first month,hen monthly until 2 months of age, every 2onths until 6 months of age, every 3 months

ntil 18 months of age, every 6 months until 2ears of age, and then yearly thereafter.108,109

Given that nutritional intake and growth maye impaired even with mild CKD in infants—nd that these improve with nutritional supple-entation17,18,110,111—it is suggested that growth

arameters be monitored at least twice as fre-uently in infants with moderate CKD as isecommended for healthy infants. More frequentvaluations are required in infants with severeKD (stages 4 to 5 and 5D). Early recognition ofrowth delay in infancy is crucial because growthailure in this critical period is extremely difficulto catch up later.16,30 Any evidence of retardedrowth in an infant should prompt detailed di-tary assessment and intervention.

In older children, the impact of CKD on growthnd body fat and lean stores appears to depend to aarge degree on the severity of CKD. A “dose-esponse” relationship between glomerular filtra-ion rate (GFR) and BMI-for-age z score was notedn 1 study, with lower GFR associated with lowerean BMI-for-age z score.28 Again, given the risks

f growth retardation in children with CKD, assess-ent of growth parameters is suggested to be

erformed at a minimum of every 6 months inhildren with CKD stages 2 to 3, ie, at least twice asften as recommended for healthy children. Forhildren with more advanced CKD (stages 4 to 5nd 5D), more frequent evaluation may be war-

anted due to the greater risk of abnormalities.

Es

meeBgifeodfco

mmcaapecmiigr

mnmci5TTliainn

noBa

An

idwbprprta

●

●

●

●

●

●

●

●

●

Recommendation 1S26

very effort should be made to conduct nutritionaltatus assessments when the child is euvolemic.

These recommendations represent the mini-um intervals for assessment. More frequent

valuation may be warranted in children withvidence of growth delay, decreasing or lowMI, any comorbidities potentially influencingrowth or nutrient intake, or recent acute changesn medical status or dietary intake. Three-dayood records at intervals more frequent thanvery 3 to 6 months are not required for infantsr children with good appetites, grossly adequateietary intakes, and adequate weight gain. Morerequent records are indicated when there isoncern about the adequacy of a child’s intake orverconsumption of 1 or more nutrients.

COMPARISON TO OTHER GUIDELINES

The Caring for Australasians with Renal Impair-ent (CARI) CKD Guidelines recommend assess-ent of dietary intake, height/length, weight, head

ircumference, and BMI at 1- to 3-month intervalsnd suggest that determination of SDS for thenthropometric measures is preferable to simplylotting on the percentile curve. They also suggestxpressing BMI relative to height-age rather thanhronological age. MAC and TSF are not recom-ended by CARI due to a lack of evidence support-

ng their use. The use of nPCR is not advocated forn the CARI nutrition guidelines, although theseuidelines were established before many of theecent studies cited were published.

The European ad hoc Committee on Assess-ent of Growth and Nutritional Status in Perito-

eal Dialysis recommends a nutritional assess-ent, including height/length, weight, head

ircumference, MAC, and BMI, at a minimumnterval of every month in children younger than

years and every 2 months for older children.SF is not recommended due to poor reliability.hey suggest assessment of dietary intake at

east every 6 months and more frequently innfants. Caution is advised in interpreting serumlbumin levels due to their poor reliability inndicating undernutrition. DXA is considered aonessential measurement tool; it is suggested

o more often than yearly. BIA also is considered

onessential since concerns with interpretabilityf BIA measures are raised. It is suggested thatIA be used only in combination with otherssessment methods.

The 2006 update of the KDOQI Pediatric HDdequacy Guidelines recommends monthlyPCR assessment.63

LIMITATIONS

Two main limitations with prior studies weredentified. Many failed to distinguish older chil-ren from infants and very young children, inhom the impact of nutrition on growth andody composition may be quite different. Manyrior studies also failed to account for CKD-elated short stature when describing body com-osition, expressing measures relative to ageather than height. This resulted in overestima-ion of deficits in weight, fat and lean masses,nd arm measures.

RESEARCH RECOMMENDATIONS

Validity of 3-day diet records and 24-hourrecalls in the CKD population in whom under-reporting of restricted foods may be common.Identification of clinically relevant biomark-ers for—and clinical predictors of—CKD-related protein-energy wasting.Determination of the prevalence of protein-energy wasting in pediatric CKD and how thisrelates to severity of CKD.Predictive value of BMI SDS in identifyingprotein-energy wasting.Identification of simple clinical markers ofprotein-energy wasting.Identification of objective methods of deter-mining volume status.Further study of nPCR is warranted to identifynPCR values reflecting adequate protein in-take for different pediatric patient age groups.The normalized PNA (nPNA) should be stud-ied as an objective measure of protein intakefor children receiving maintenance PD.Further work to develop and validate multipa-rameter nutritional assessment scales, such as

the SGA, is warranted.

map

tccpo

2

2

2

nmds<g

gtipa

A

RECOMMENDATION 2: GROWTH

ti

P

ticrtsscfeuitibfotwF(a

S

tttasmg

R

oatldcvic

INTRODUCTION

Growth failure and linear height deficit are theost visible complications of CKD in children

nd are associated with serious medical andsychological comorbidities.Early nutritional intervention and the preven-

ion and treatment of metabolic deficits are keyomponents in the preservation of growth in ahild with CKD. In children who demonstrateoor growth despite these measures, the additionf rhGH therapy can be beneficial.

.1 Identification and treatment of existingnutritional deficiencies and metabolic ab-normalities should be aggressively pur-sued in children with CKD stages 2 to 5and 5D, short stature (height SDS <�1.88 or height-for-age < 3rd percentile),and potential for linear growth. (A)

.2 The serum bicarbonate level should becorrected to at least the lower limit ofnormal (22 mmol/L) in children withCKD stages 2 to 5 and 5D. (B)

.3 rhGH therapy should be considered inchildren with CKD stages 2 to 5 and 5D,short stature (height SDS < �1.88 orheight-for-age < 3rd percentile), andpotential for linear growth if growthfailure (height velocity-for-age SDS <�1.88 or height velocity-for-age < 3rdpercentile) persists beyond 3 monthsdespite treatment of nutritional deficien-cies and metabolic abnormalities. (B)

RATIONALE

2.1: Identification and treatment of existingutritional deficiencies and metabolic abnor-alities should be aggressively pursued in chil-

ren with CKD stages 2 to 5 and 5D, shorttature (height SDS < �1.88 or height-for-age

3rd percentile), and potential for linearrowth. (A)A variety of factors can contribute to the poor

rowth seen in children with CKD.112 Interven-ions to normalize inadequate protein and calorientake, water and electrolyte losses in those witholyuric and salt-wasting conditions, metabolic

cidosis (see Recommendation 2.2), renal os- b

merican Journal of Kidney Diseases, Vol 53, No 3, Suppl 2 (Marc

eodystrophy, and resistance to hormones mediat-ng growth must be aggressively managed.

rotein-EnergyMalnutrition

Caloric deficiency and abnormal protein me-abolism may have an important role in growthmpairment, particularly in infants and youngerhildren.113 Reduced caloric intake may be aesult of anorexia, emotional distress, alteredaste sensation, or nausea and vomiting. Priortudies provided evidence that energy intakeignificantly correlated with growth velocity inhildren with CKD that developed during in-ancy, such that normal growth occurred if en-rgy intake exceeded 80% of recommended val-es, whereas it would be expected to cease ifntake decreased to less than 40%.114 Early nutri-ional interventions, including tube feeding innfants, and prevention and treatment of meta-olic deficits of CKD are fundamental measuresor preventing severe stunting in the first 2 yearsf life.111,115 Studies also have shown that nutri-ional supplementation in malnourished childrenith CKD can result in improved growth.18,111,116

inally, there is recent evidence that frequentdaily) HD is associated with enhanced nutritionnd a normal height velocity.117

altWasting

Infants with renal dysplasia typically exhibithe most severe height deficits, which may reflecthe age at onset of kidney disease, degree ofubular abnormality inherent in the condition,nd the resultant loss of sodium and other sub-tances important for growth.118 Thus, salt supple-entation for a polyuric infant with CKD who is

rowing poorly may be therapeutic.111,119,120

enalOsteodystrophy

Growth can be adversely affected by renalsteodystrophy. Renal osteodystrophy representsrange of disorders, from secondary hyperpara-

hyroidism and high-turnover bone disease toow-turnover osteomalacia and adynamic boneisease.118 Secondary hyperparathyroidism mayause growth failure by modulating genes in-olved in endochondral bone formation and alter-ng the architecture of the growth plate. A keyomponent of the management of high-turnover

one disease is control of serum phosphorus

h), 2009: pp S27-S30 S27

lsfbcor

C

semvssdtbsltcscs

rm5

tbrwt

wmgrosaaahhdti

tpfls

lcdHmstifacicsat

sacnd1rtaba

csaga3tb

tsirmgd

Recommendation 2S28

evel. Dietary and medication therapy are de-igned to target a normal serum phosphorus levelor age. The prevention/correction of adynamicone disease requires close monitoring of dietaryalcium intake and vitamin D therapy with a goalf maintaining serum calcium level in the normalange.121

orticosteroids

The use of corticosteroids can lead to suppres-ion of growth in children with CKD by theirffect on the integrity of the somatotropic hor-one axis.122 The action of corticosteroids is at

arious levels of the axis and involves suppres-ion of pituitary growth hormone release bytimulating hypothalamic somatostatin tone,ownregulation of hepatic growth hormone recep-ors, inhibition of insulin-like growth factor (IGF)ioactivity, alteration of the IGF-binding proteinerum profile, and a direct suppressive effect onocal growth factor and tissue matrix produc-ion.123 Discontinuing or modifying the dose oforticosteroids is in turn desirable from the per-pective of growth as long as the patient’s medi-al condition that prompted the use of the cortico-teroids is not exacerbated.

2.2: Serum bicarbonate level should be cor-ected to at least the lower limit of normal (22mol/L) in children with CKD stages 2 to 5 and

D. (B)CKD-induced acidosis impedes statural growth

hrough a variety of mechanisms, which lead tooth endogenous growth hormone and rhGHesistance. Optimal growth in children with CKDill be achieved with acid-base status normaliza-

ion.Metabolic acidosis develops in adult patients

ith CKD stages 4 to 5.25,26 Metabolic acidosisay impede statural growth through a number of

rowth factor–specific mechanisms, includingeduction in thyroid hormone levels and bluntingf IGF response to rhGH, which has been demon-trated in healthy adult patients after long-termcid loading.124,125 Animal data also suggest ancidosis-induced human growth hormone–IGF-1xis impairment118 by decreasing pulsatile growthormone secretion,126 hepatic IGF-1 and growthormone receptor messenger RNA (mRNA) pro-uction,127 and IGF-1 expression at the level ofhe chondrocyte.128 Metabolic acidosis also can

mpede growth through mechanisms not specific c

o growth factor impairment, such as increasedrotein catabolism,129,130 increased calcium ef-ux from bone,131,132 and decreased albuminynthesis.133

No data exist to evaluate the efficacy of iso-ated acidosis correction on growth failure inhildren with CKD, likely because growth retar-ation in children with CKD is multifactorial.112

owever, data show a profound growth improve-ent in children with isolated renal tubular acido-

is treated with alkali therapy.134,135 Becausehese studies showed that maximal height wasnversely related to the duration of acidosis be-ore therapy, oral alkali therapy should be initi-ted when persistent acidosis is observed inhildren with CKD. Oral alkali can be prescribedn the form of sodium bicarbonate or sodiumitrate preparations, but citrate preparationshould not be prescribed to patients receivingluminum-based phosphorus binders because ci-rate enhances enteral aluminum absorption.

In children on dialysis therapy who have per-istent acidosis, a trial of increased dialysis dosend/or a higher bicarbonate bath concentrationan be considered to correct acidosis. Althougho studies evaluated the effect of increasingialysis dose in patients with persistent acidosis,

pediatric study demonstrated better growthates in children receiving continuous ambula-ory PD (CAPD) versus continuous cycler-ssisted PD (CCPD) versus HD that may haveeen explained partially by better uremic controlnd acidosis correction by using CAPD.136

2.3: rhGH therapy should be considered inhildren with CKD stages 2 to 5 and 5D, shorttature (height SDS < �1.88 or height-for-ge < 3rd percentile), and potential for linearrowth if growth failure (height velocity-for-ge SDS < �1.88 or height velocity-for-age <rd percentile) persists beyond 3 months despitereatment of nutritional deficiencies and meta-olic abnormalities. (B)The growth hormone–IGF-1 axis is an impor-

ant regulator of growth and metabolism, andubstantial abnormalities in the axis have beendentified in children with CKD, all of whichesult in growth hormone resistance. These abnor-alities include decreased expression of the

rowth hormone receptor, impaired signal trans-uction of the growth hormone receptor, de-

reased production of IGF-1, and decreased

atirw

U

alFrphrmfiatiia

msdtifitdIiCmrwop

U

ttptet

ea

U

tshtFstety

●

●

●

●

●

●

Growth S29

ctivity of IGF by inhibitory IGF-binding pro-eins.112,123,137 Despite the presence of thesenhibitory factors, the use of rhGH regularlyesults in improved height velocity in childrenith CKD.112,137-141

se inCKDStages 2 to 5

Clinical trials have demonstrated the safetynd efficacy of rhGH therapy in promotinginear growth in children with CKD.112,142

ifteen randomized clinical trials examininghGH versus placebo have demonstrated im-rovement in height SDS, height velocity, andeight velocity SDS, with the most dramaticesponse occurring in the first year of treat-ent followed by a progressively reduced ef-

ect thereafter. The target height deficit at thenitiation of therapy and duration of treatmentre the most important predictors of cumula-ive height gain.143 Long-term rhGH therapyn children with CKD has been shown to resultn catch-up growth, and many patients achievefinal height within the normal range.32,143-146

Hokken-Koelega et al145 found that treat-ent during puberty was associated with a

ustained improvement in height SDS withouteleterious effects on GFR and bone matura-ion. Treatment showed no significant increasen the incidence of malignancy, slipped capitalemoral epiphysis, avascular necrosis, glucosentolerance, pancreatitis, progressive deteriora-ion in renal function, fluid retention, or inci-ence of benign intracranial hypertension.112

n a recent analysis of data contained in annternational growth database of children withKD, Nissel et al143 revealed that the incre-ent in height SDS during the first year of

hGH treatment was greatest in patients whoere prepubertal and experienced a normalnset of puberty and those who had earlyuberty.

se inDialysis Patients

Clinical studies support the efficacy of rhGHherapy in patients requiring kidney replacementherapy. Whereas children receiving dialysis ex-erience an increase in growth with rhGH therapy,he response is less than that of patients witharlier stages of CKD, thus emphasizing the need

o initiate rhGH therapy at a young age and/or

arly in the evolution of CKD to maximize thechievement of growth potential.32,143,144

se in Transplant Patients

Poor growth outcomes after kidney transplan-ation are associated with corticosteroid use, per-istent CKD, and abnormalities of the growthormone–IGF-1 axis. The use of rhGH afterransplantation does lead to catch-up growth, andine et al147 demonstrated that final height wasuperior in rhGH-treated kidney transplant pa-ients compared with controls, with no adverseffect on allograft function. In most cases, initia-ion of rhGH therapy has been delayed until 1ear or more after kidney transplantation.147

COMPARISON TO OTHER GUIDELINES

The CARI CKD Guidelines recommend thatrhGH therapy be offered to short children(height � 25th percentile for chronologicalage, height velocity � 25th percentile forbone age) with CKD stages 2 to 5 and 5D.The European Pediatric Peritoneal DialysisWorking Group recommends that rhGH beconsidered in PD patients with growth poten-tial only after nutritional parameters, withacidosis, hyperphosphatemia, and secondaryhyperparathyroidism have been corrected.The CARI CKD Guidelines also recommendnormalization of serum bicarbonate level togreater than 22 mmol/L in patients with CKD.

LIMITATIONS

The lack of randomized controlled trials inchildren on dialysis therapy and after transplan-tation is an obstacle to our understanding ofwhom to treat with rhGH and what dose to useto achieve the best possible growth.Because CKD-related growth failure and thenature of acidosis are often multifactorial, fewstudies will be able to address the acidosis-related contributions directly. It would beunethical to prospectively randomly assignchildren to an acidosis arm given the knownadverse effects of acidosis.

RESEARCH RECOMMENDATIONS

Evaluations of rhGH dosing regimens that are

titrated to the level of IGF-1.

●

●

●

●

●

Recommendation 2S30

Study of non–growth-related benefits of rhGHtherapy in children, such as psychosocial andquality-of-life benefits, bone development, neu-rodevelopment, and cardiovascular benefits.Evaluation of methods to overcome the pooruse of rhGH in children with CKD and poorgrowth.148

Study of the pathophysiological factors con-tributing to poorer response to rhGH in chil-dren on dialysis therapy compared with chil-dren before dialysis therapy.Further study of the impact of frequentHD on growth, with or without the use of

rhGH.

Studies of the effect of CKD-related acidosisand its treatment will need to assess childrenwho are acidotic at baseline because it wouldbe unethical to randomly assign children to anacidosis arm prospectively. The clinical andanimal model data cited argue for correctionof or controlling for the presence of acidosis inany study assessing growth outcomes in pedi-atric patients with CKD. Recent preliminarydata for more frequent or intensive HD demon-strate improved growth profiles149,150 thatcould be explained in part by improved acid-base status. Such studies should be expanded

in the future.

rcgodrwtAccncpckm

3

3

3

3

A

RECOMMENDATION 3: NUTRITIONAL MANAGEMENT AND

COUNSELING

vb5

tidlCmdointaldepbs

ttbftstwpmDpeF

INTRODUCTION

Malnutrition, growth delay, and nutrition-elated metabolic abnormalities are common inhildren with CKD and are associated with areater risk of morbidity and mortality. Numer-us studies of infants and young children haveocumented energy intakes less than 80% ofecommendations,9,151,152 with reversal of botheight loss and poor growth when nutritional

herapy is provided to meet recommendations.lthough other factors are involved, nutritional

are and therapy are essential to prevent ororrect these disturbances and are vital compo-ents of the multidisciplinary management ofhildren with CKD. Individualized nutrition carelans require frequent modification according tohanges in the child’s age, development, residualidney function, and mode of kidney replace-ent therapy.

.1 Nutrition counseling based on an indi-vidualized assessment and plan of careshould be considered for children withCKD stages 2 to 5 and 5D and theircaregivers. (B)

.2 Nutritional intervention that is individual-ized according to results of the nutritionalassessment and with consideration of thechild’s age, development, food prefer-ences, cultural beliefs, and psychosocialstatus should be considered for childrenwith CKD stages 2 to 5 and 5D. (B)

.3 Frequent reevaluation and modificationof the nutrition plan of care are suggestedfor children with CKD stages 2 to 5 and5D. (C) More frequent review is indicatedfor infants and children with advancedstages of CKD, relevant comorbiditiesinfluencing growth or nutrient intake,and evidence of inadequate intake ormalnutrition or if acute illness or adverseevents occur that may negatively impacton the nutritional status. (C)

.4 Nutritional management coordinated bya dietitian who ideally has expertise inpediatric and renal nutrition is suggested

for children with CKD stages 2 to 5 and b

merican Journal of Kidney Diseases, Vol 53, No 3, Suppl 2 (Marc

5D. (C) It is suggested that nutritionalmanagement be a collaborative effort in-volving the child, caregiver, dietitian, andother members of the multidisciplinarypediatric nephrology team (ie, nurses,social workers, therapists, and nephrolo-gists). (C)

RATIONALE

3.1: Nutrition counseling based on an indi-idualized assessment and plan of care shoulde considered for children with CKD stages 2 toand 5D and their caregivers. (B)Children with CKD frequently have poor appe-

ites and require modification of dietary nutrientntake to maintain optimal nutrition, growth, andevelopment. Studies have shown that the ca-oric intake of infants and young children withKD is frequently less than 80% of recom-ended intake,9,151,152 and that low intakes and

ecreased rates of weight gain and growth mayccur early in those with CKD and worsen withncreasing severity of CKD.9,28,153 Correction ofutritional deficits through enhanced nutrition inhe form of oral supplements and/or tube feedingchieves catch-up weight gain for all and catch-upinear growth for infants and young chil-ren.17,18,111,150,154-156 Alterations to fluid or di-tary intake of protein, carbohydrate and/or fat,hosphorus, sodium, potassium, or calcium maye required. Vitamin, mineral, or trace elementupplements also may be needed.

Nutrition counseling is performed based onhe nutritional assessment and nutrition prescrip-ion and is recommended on a frequent basisecause of the dynamic nature of a child’s growth,ood preferences, development, medical condi-ion, and level of independence. Intensive coun-eling should occur at the time of initial presenta-ion; when undesirable changes in appetite,eight gain, linear growth, blood work, bloodressure, or fluid balance occur; or when theethod of kidney replacement therapy is altered.ietary counseling should be positive in nature,roviding information about foods the child canat to replace foods that they must limit or avoid.amily members and primary caregivers should

e involved in the education process to be sure

h), 2009: pp S31-S34 S31

tpambt

trttAnaccig

aaale5

●

●●

●●

●

●

t

●

●

●

froqcdiTatsrhdg

iifieaipwtoiCfitRmplaetaftli

ocMar

Recommendation 3S32

he child has appropriate foods available and torovide consistent support for recommended foodnd fluid modifications, as well as encourage-ent for nutrient consumption. Counseling must

e targeted at the appropriate education level ofhe child and family member.

Evidence from studies using dietary interven-ion indicates that frequent nutrition counselingesults in adherence and improved outcomes inhe general pediatric population157-159; however,here are limited studies of the CKD population.

randomized controlled trial of individualizedutritional counseling and frequent follow-up indults with CKD stages 4 or 5 showed positivehanges in energy intake, nutritional status ac-ording to SGA, and body cell mass in thentervention group compared with the controlroup.160

3.2: Nutritional intervention that is individu-lized according to results of the nutritionalssessment and with consideration of the child’sge development, food preferences, cultural be-iefs, and psychosocial status should be consid-red for children with CKD stages 2 to 5 andD. (B)Indications for nutritional intervention include:

impaired ability to ingest or tolerate oralfeedings,1

increased metabolic requirements,1

documented inadequate provision or toleranceof nutrients,1

acute weight loss of 10% or more,1

a BMI value less than 5th percentile forheight-age (underweight) or greater than 85thpercentile (overweight),inadequate weight gain, length/height morethan 2 SDs below the mean (�3rd percentile),or a significant decrease in usual growthpercentile,abnormalities in nutrition-related biochemis-tries.

Neonates should also be considered at nutri-ional risk if they are preterm or have:

low birth weight (�2,500 g) even in theabsence of gastrointestinal, pulmonary, or car-diac disorders,a birth weight z score less than �2 SDs (�3rdpercentile) for gestational age,1

polyuria and inability to concentrate urine. n

In addition to providing fuel for the body tounction, food and beverages have an importantole in family and social life and induce feelingsf satisfaction, pleasure, and comfort. Promotinguality of life and patient satisfaction is a criticalomponent of effective health care; therefore,iet and fluid restrictions should be individual-zed and imposed only when clearly needed.hey should be kept as liberal as possible tochieve recommended energy and protein in-akes and optimal weight gain and growth. Re-trictions can be adjusted based on responses inelevant parameters. Children who are polyuric,ave residual kidney function, or are on dailyialysis therapy149 typically require less strin-ent restrictions.Promoting satisfaction with a prescribed diet

s an important component of effective nutritionntervention. Many factors are involved in satis-action with and adherence to prescribed diets,ncluding the complexity of the diets and differ-nces between the patient’s typical eating patternnd the prescribed one. An eating pattern thatncorporates personal, ethnic, and cultural foodreferences and gives satisfaction and pleasurehile meeting prescribed medical recommenda-

ions is likely to support long-term maintenancef dietary changes.161 The Modification of Dietn Renal Disease (MDRD) Study of adults withKD measured patient satisfaction with modi-ed protein and phosphorus eating patterns and

he relationship of satisfaction to adherence.162

esults showed that satisfaction decreased as theagnitude of diet changes increased, and that

atient adherence to diet modification was re-ated to their satisfaction with diet. In a study ofdult Hispanic patients on HD therapy, knowl-dge of the renal diet, food-frequency consump-ion, socioeconomic status, family support, andttitudes toward the renal diet were identified asactors that influenced dietary adherence.163 Pa-ient education provided in the patient’s nativeanguage also was an important element promot-ng adherence.

3.3: Frequent reevaluation and modificationf the nutrition plan of care is suggested forhildren with CKD stages 2 to 5 and 5D. (C)ore frequent review is indicated for infants

nd children with advanced stages of CKD,elevant comorbidities influencing growth or

utrient intake, evidence of inadequate intake

oen

tdticaprtCouseprgatdb

maaioItailitiiSnw(cct

ifl

aotpc

aawscgdng

idotnqtemsdctmdepns

ttvrhtp

rdlhte

Nutritional Management and Counseling S33

r malnutrition, or if acute illness or adversevents occur that may negatively impact on theutritional status. (C)The nutrition plan of care synthesizes informa-

ion obtained from the nutritional assessment toetermine short- and long-term goals from whichhe nutrition prescription and plan for individual-zed nutritional therapy is developed. The plan ofare is developed in collaboration with the childnd caregivers and shared with the multidisci-linary team. The nutrition care plan should beeviewed often with the child and all caregiverso keep them informed and improve adherence.onditions that dictate more frequent evaluationf the nutrition plan of care include young age;nfavorable changes in anthropometric mea-ures, oral intake, gastrointestinal function, nutri-nt-related laboratory values, or fluid or bloodressure status; indication of nonadherence withecommendations; prolonged or large doses oflucocorticosteroids; change in psychosocial situ-tion; or when placement of an enteral feedingube is under consideration. In these cases, up-ates to the care plan monthly or more often maye necessary.Studies reporting stabilization or improve-ent in growth parameters with nutritional care

nd therapy have involved a multidisciplinarypproach with frequent assessments and counsel-ng by pediatric renal dietitians, many of whichccurred at least monthly.17,18,149,150,156,164,165

n a prospective longitudinal study to estimatehe amount of dietetic care necessary to supportnd achieve adequate nutritional intake for growthn children (n � 13; age, 0.2 to 8.5 years) onong-term PD therapy with or without tube feed-ng, all direct and indirect contacts by the dieti-ian were recorded over a 3-year period.164 Dur-ng this time, mean weight SDS and BMI SDSmproved (weight SDS, �1.32 to �0.73; BMIDS, �0.91 to 0.17; P � 0.03). The meanumber of dietetic contacts per patient per monthas greater for children younger than 5 years

n � 5; 5.9 � 1.9) compared with the olderhildren (n � 8; 3.1 � 1.6). The majority of allontacts (82%) were with children with feedingubes (n � 8).

In the MDRD Study,166 a variety of counsel-ng strategies and sustained monthly supportrom dietitians helped prevent relapse and stimu-

ated study participants’ ability to improve their d

pplication of skills over time.167 This was dem-nstrated in the follow-up period by the ability ofhe patients on the low-protein and very-low-rotein diets to adhere to modifications and de-rease their protein intake further over time.

3.4: Nutritional management coordinated bydietitian who ideally has expertise in pediatricnd renal nutrition is suggested for childrenith CKD stages 2 to 5 and 5D. (C) It is

uggested that nutritional management be aollaborative effort involving the child, care-iver, dietitian, and other members of the multi-isciplinary pediatric nephrology team (ie,urses, social workers, therapists, and nephrolo-ists). (C)A registered dietitian should be a central and

ntegral part of dietary management. Registeredietitians are proficient in the assessment andngoing evaluation of the patient’s nutrition sta-us and development of the diet prescription andutrition care plan. The pediatric population re-uires a registered dietitian skilled in the evalua-ion of growth and the physical, developmental,ducational, and social needs of children. At ainimum, registered dietitians should be respon-

ible for assessing the child’s nutritional status;eveloping the nutrition plan of care; providingulturally sensitive education and counseling athe appropriate age level for patients, familyembers, and/or caregivers; making recommen-

ations for implementing and adjusting oral,nteral, and parenteral nutrition; monitoring theatient’s progress, including adherence to theutrition prescription and documentation of theseervices.

Early involvement of occupational or speechherapists and pediatric psychologists or psychia-rists who specialize in feeding problems is in-aluable for managing chewing/swallowing/food-efusal issues in toddlers, avoiding oralypersensitivity in tube-fed infants, and enablinghe smooth transition from tube feeding to com-lete oral feeds after transplantation.17,154,168,169

Nonadherence to dietary modifications is aecurring problem for children, especially in chil-ren lacking family support or adolescents rebel-ing against parental supervision. However, thereas been limited study of dietary compliance inhis population. In 2 prospective studies, adher-nce to a low-sodium diet was poor165 and a

ecrease in use of nutritional supplements was

ocfteip1ctctanawaptafii

aftattdmnGf

attc

●

●

tpstats

●

●

Recommendation 3S34

bserved during a 2-year period despite intensiveounseling to continue their use.156 A programor the maintenance of special diets based on aoken system of reinforcement was successful inffecting improved dietary behaviors related tontradialytic weight gain and excessive dietaryrotein and potassium intake in 4 children (aged1 to 18 years) on HD therapy with longstandingompliance issues.170 Social workers, child lifeherapists, and nurses can provide additionaloping strategies to children and families to helphem deal with the frustrations and burdensround feeding problems, diet restrictions, andutritional support and improve their ability todhere to new regimens. Pharmacists can workith children and families to find the most accept-

ble liquid or solid form of such medications ashosphate binders, iron supplements, renal mul-ivitamins, and gastrointestinal motility agentsnd help them develop medication schedules thatt their feeding schedule and lifestyle and result

n optimal drug effectiveness.The financial burden of dietary manipulation

nd nutritional supplementation can be excessiveor some families, and social workers can iden-ify sources of funding and facilitate fundingpplications for eligible families. As examples,he daily cost to a family of providing an addi-ional 250 calories through commercial carbohy-rate modules (glucose polymers) is approxi-ately $2.00, and the cost of providing 100% of

utritional needs to a 3-year-old child through-tube feeding using a commercial adult renal

eeding product is about $14.30.Collaboration and good communication among

ll members of a family-centered team best suithe needs of the child and family and workoward achieving the ideal outcomes for the

hild.156,165,171

COMPARISON TO OTHER GUIDELINES

The 2005 CARI Guidelines on Nutrition andGrowth in Kidney Disease state that nutritionalassessment and counseling is regarded as manda-tory in the management of children with CKDand suggest that nutritional assessment andcounseling by a pediatric renal dietitian shouldtake place at 1- to 3-month intervals.172

The American Heart Association ScientificStatement on cardiovascular risk reduction inhigh-risk pediatric patients, including thosewith CKD, recommends initial rigorous age-appropriate diet counseling by a dietitianfollowed by specific diet/weight follow-upevery 2 to 4 weeks for 6 months.173

LIMITATIONS

Whereas it is assumed that consistent promo-ion of the benefits of dietary modification androvision of practical information and emotionalupport to children and their families can posi-ively influence adherence and clinical outcomesnd minimize stress around nutritional issues,here have been no high-quality studies to demon-trate such results in children with CKD.

RESEARCH RECOMMENDATIONS

The effect of intensive and frequent dietarycounseling for nutritional intake, nutritionalstatus, quality of life, and occurrence ofnutrition-related morbidities should be evalu-ated at various stages of CKD to identify howearly in the progression of CKD nutritionintervention should occur and aid in determin-ing adequate allocation of pediatric renaldietitians within programs.Studies are needed to evaluate strategies toenhance dietary adherence, with particular

emphasis on the adolescent age group.

wacraeasw

4

4

4

4

4

A

RECOMMENDATION 4: ENERGY REQUIREMENTS AND THERAPY

4

CtiBsw

5deecariabwmptmSttcwtigfnaatmepsc

INTRODUCTION

Poor energy intake is common in childrenith CKD stages 2 to 5 and 5D due to reduced

ppetite and vomiting. Early intervention is criti-al with the introduction of tube feeds if energyequirements cannot be met by the oral routelone. A smaller percentage of children havexcessive energy intake, and dietary interventionnd lifestyle changes are needed to address thehort- and long-term complications of over-eight and obesity.

.1 Energy requirements for children withCKD stages 2 to 5 and 5D should beconsidered to be 100% of the EER forchronological age, individually adjustedfor PAL and body size (ie, BMI). (B)Further adjustment to energy intake issuggested based upon the response in rateof weight gain or loss. (B)

.2 Supplemental nutritional support shouldbe considered when the usual intake of achild with CKD stages 2 to 5 or 5D failsto meet his or her energy requirementsand the child is not achieving expectedrates of weight gain and/or growth forage. (B)

.3 Oral intake of an energy-dense diet andcommercial nutritional supplementsshould be considered the preferred routefor supplemental nutritional support forchildren with CKD stages 2 to 5 and 5D.(B) When energy requirements cannot bemet with oral supplementation, tube feed-ing should be considered. (B)

.4 A trial of IDPN to augment inadequatenutritional intake is suggested for mal-nourished children (BMI-for-height-age< 5th percentile) receiving maintenanceHD who are unable to meet their nutri-tional requirements through oral and tubefeeding. (C)

.5 A balance of calories from carbohydrateand unsaturated fats within the physiolog-ical ranges recommended as the AMDR ofthe DRI is suggested when prescribingoral, enteral, or parenteral energy supple-mentation to children with CKD stages 2

to 5 and 5D. (C) d

merican Journal of Kidney Diseases, Vol 53, No 3, Suppl 2 (Marc

.6 Dietary and lifestyle changes are sug-gested to achieve weight control in over-weight or obese children with CKD stages2 to 5 and 5D. (C)

RATIONALE

4.1: Energy requirements for children withKD stages 2 to 5 and 5D should be considered

o be 100% of the EER for chronological age,ndividually adjusted for PAL and body size (ie,MI). Further adjustment to energy intake is

uggested based upon the response in rate ofeight gain or loss. (B)In children with CKD (excluding CKD stage

), spontaneous energy intake decreases witheteriorating kidney function,28 but there is novidence that children with CKD have differ-nt energy requirements than those for healthyhildren. In a recent study of 25 children anddolescents with CKD stage 5 on HD therapy,esting energy expenditure measured by usingndirect calorimetry was the same as for healthyge-matched controls when adjusted for leanody mass.174 In 65 children aged 2 to 16 yearsith conservatively managed CKD (GFR � 75L/min/1.73 m2), regular dietetic advice with

articular attention to optimizing energy in-ake with or without the use of supplementsaintained or significantly increased the heightDS with an energy intake maintained within

he normal range.156 In 35 children youngerhan 5 years with CKD stages 4 to 5, signifi-ant weight gain and accelerated linear growthas clearly demonstrated in those starting en-

eral feeding at age younger than 2 years;mproved weight gain and maintenance ofrowth was observed in those starting enteraleeds at age 2 to 5 years without exceedingormal energy requirements.18 The findingsre similar to an earlier study of 22 childrenge 0.2 to 10 years on long-term dialysisherapy in which there was significant improve-

ent in both height and weight SDS with annergy intake within the normal range.154 Im-roved linear growth also has been demon-trated in 12 prepubertal or early pubertalhildren on HD therapy with increased time on

ialysis and close monitoring of nutritional

h), 2009: pp S35-S47 S35

i9Tstpg

stiPoyfeieu

cioheormiFmwed

asb

mepsiqwti

osiinfww

wfoietc

04713

9

3

Recommendation 4S36

ntake. This was achieved with an intake of0.6% of the recommended energy intake.150

he importance of caloric intake has also beenhown in 31 prepubertal children on dialysisherapy treated with growth hormone, with aositive correlation between energy intake androwth velocity.26

All children with CKD stages 2 to 5 and 5Dhould have regular dietary assessments, withhe frequency dependent on the degree of renalmpairment to ensure EER for age, sex, andAL (Tables 2 to 4; Appendix 2, Table 34 fornline calculator) are achieved. If childrenounger than 3 years with a length- or height-or-age less than �1.88 SDS fail to achievexpected weight gain and growth when receiv-ng EER (Table 2) based on chronological age,stimated requirements may be modified bysing height-age.As in the general public, the incidence of

hildhood obesity in those with CKD is increas-ng. National registry data for pediatric dialysisr transplant patients showed a significantlyigher mortality rate at the upper and lowerxtremes of BMI-for-age.49 Pretransplantationbesity is associated with decreased long-termenal allograft survival.176 Prevention and treat-ent of obesity in patients with CKD is also

mportant to reduce the risk of hyperlipidemia.at mass is less metabolically active than leanass; therefore, energy requirements for over-eight or obese children are lower and can be

stimated by using equations specific for chil-ren heavier than a healthy weight (Table 3).In infancy, feeds should be of breast milk orwhey-based infant formula with a low renal

olute load if needed. Weaning solids should

Table 2. Equations to Estimate Energy R

Age Estimated Energy Require

-3 mo EER � [89 � weight (kg) �-6 mo EER � [89 � weight (kg) �-12 mo EER � [89 � weight (kg) �3-35 mo EER � [89 � weight (kg) �-8 y Boys: EER � 88.5 � 61.9

Girls: EER � 135.3 � 30.8-18 y Boys: EER � 88.5 � 61.9

Girls: EER � 135.3 � 30.8

Source: ref 175.See Appendix 2.

e introduced at the same time as recom-

ended for healthy children. In children, high-nergy foods and drinks are recommended asart of a controlled intake, with nutritionalupplements or nutritionally complete feedsntroduced if necessary. Calculated energy re-uirements are estimates, and some childrenill require more or less for normal growth;

herefore, all dietary prescriptions should bendividualized.

Early intervention to try to prevent the devel-pment of oral hypersensitivity and food-aver-ive behavior often is incorporated into the feed-ng plan and includes the correct timing forntroduction of solids with gradual inclusion ofew tastes and lumpier textures, messy play andood exploration, prohibition of force feedingith self-feeding behavior promoted, and sittingith the family at meal times.Other members of the multidisciplinary team

ith expertise in infant feeding issues—eg, in-ant psychologists and speech, language, andccupational therapists—may be important inmproving the outcome for normal feeding. How-ver, overemphasis on maintaining the oral routeo achieve an adequate nutritional intake may beounterproductive because symptoms may be

ements for Children at Healthy Weights

ER) (kcal/d) � Total Energy Expenditure � Energy Deposition

� 175� 56� 22� 20(y) � PA � [26.7 � weight (kg) � 903 � height (m)] � 20(y) � PA � [10 � weight (kg) � 934 � height (m)] � 20

(y) � PA � [26.7 � weight (kg) � 903 � height (m)] � 25(y) � PA � [10 � weight (kg) � 934 � height (m)] � 25

Table 3. Equations to Estimate Energy Requirementsfor Children Ages 3 to 18 Years Who Are Overweight

AgeWeight Maintenance Total Energy Expenditure (TEE)

in Overweight Children

-18 y Boys: TEE � 114 � [50.9 � age (y)] �PA � [19.5 � weight (kg) � 1161.4 �height (m)]

Girls: TEE � 389 � [41.2 � age (y)] �PA � [15.0 � weight (kg) � 701.6 �height (m)]

equir

ment (E

100]100]100]100]

� age� age

� age� age

Source: ref 175.

etm

tfoaafubsccotnKrvpcPestpHfrerifltflm

bwhag

cctsmt

itciitBtiwcrtcgcmuc(3d

BG

d nd Gov

Energy Requirements and Therapy S37

xacerbated by inappropriate expectations andhe critical period of intervention to ensure nor-al nutrition dependent growth may be missed.In children with CKD stage 5D on PD

herapy, variable glucose absorption takes placerom the dialysis fluid depending on the modef dialysis, dialysate glucose concentration,nd peritoneal membrane capacity. There are 2dult studies documenting the caloric impactrom dialysis fluid glucose.177,178 One formulasing both PD modality and peritoneal equili-ration test (PET) transport characteristics washown to closely approximate measured glu-ose absorption, but has not been evaluated inhildren.177 In a pediatric study of 31 childrenlder than 3 years on ambulatory PD therapy,he mean energy intake derived from perito-eal glucose absorption was 9 kcal/kg/d.152

aiser et al136 demonstrated better growthates in children receiving CAPD versus CCPDersus HD that may have been partially ex-lained by increased glucose absorption asso-iated with CAPD. Because many children onD therapy are underweight, the prescribednergy intake in those with CKD stage 5Dhould exclude the estimated calorie absorp-ion from the dialysate because this may com-romise the nutritional quality of the diet.owever, some children—and particularly in-

ants on PD therapy—gain weight at a fasterate than normal despite oral and/or enteralnergy intakes that are lower than the averageequirements. Reduced physical activity andncreased exposure to dialysate glucose foruid removal may be explanations, and in

hese cases, the calorie contribution from PDuid should be taken into account when esti-

Table 4. Physical Activity Coefficients for Determinat

Gender

Lev

Sedentary Low Active

Typical activities of dailyliving (ADL) only

ADL � 30-60 min ofmoderate activity (walking at 5-7 km/

oys 1.0 1.13irls 1.0 1.16

Source: Health Canada: http://www.hc-sc.gc.ca/fn-anuced with the permission of the Minister of Public Works a

ating energy requirements. s

4.2: Supplemental nutritional support shoulde considered when the usual intake of a childith CKD stages 2 to 5 or 5D fails to meet his orer energy requirements and the child is notchieving expected rates of weight gain and/orrowth for age. (B)4.3: Oral intake of an energy-dense diet and

ommercial nutritional supplements should beonsidered the preferred route for supplemen-al nutritional support for children with CKDtages 2 to 5 and 5D. (B) When energy require-ents cannot be met with oral supplementa-

ion, tube feeding should be considered. (B)Energy requirements in infants and children

nclude the energy needed for tissue deposi-ion, with satisfactory growth a sensitive indi-ator of whether energy requirements are be-ng met, particularly in infancy.179 Poor energyntake and vomiting in children with CKDherefore will have an adverse effect on growth.ecause short stature at dialysis therapy initia-

ion is a marker for poor outcome in childrennitiating dialysis therapy, early interventionith intensive nutritional support may be criti-

al to outcome.180 Because calculated energyequirements are estimates, all dietary prescrip-ions should be individualized because somehildren will require more or less for normalrowth. Formulas and enteral feedings may beoncentrated and/or supplemented with a com-ercial glucose polymer powder and/or a liq-

id fat. Energy-dense feeds may be needed inhildren with CKD stage 5 with oligoanuriasee Tables 2 to 4 for EER; Appendix 2, Table4, for resources to calculate EER; and Appen-ix 3, Table 36, for information for feeds and

Energy Requirements in Children Ages 3 to 18 Years

ysical Activity

Active Very Active

ADL � �60 min ofdaily moderateactivity

ADL � �60 min of daily moderateactivity � an additional 60 minof vigorous activity or 120 minof moderate activity

1.26 1.421.31 1.56

mats/hpfb-dgpsa/pdf/nutrition/dri_tables-eng.pdf. Repro-ernment Services Canada, 2008.

ion of

el of Ph

dailyeg,h)

/alt_for

upplements).

chttratetmtettrcvlrw

ftcmfiaatdspmabglia

nmfpotslw

ssnaasthtwsditm8artylhSchCsitntyiRto(sccmc3dgSgati

Recommendation 4S38

However, both poor appetite and vomiting areommon in infants and children with CKD andave a negative impact on the aim of achievinghe dietary prescription. Poor appetite is multifac-orial in origin and includes a thirst for waterather than feed in those with polyuric CKD, thedministration of multiple unpleasant medica-ions, and a preference for salty rather thannergy-dense sweetened foods. The accumula-ion of appetite-regulating cytokines and hor-ones has been implicated in the cause of both

his lack of spontaneous appetite and early sati-ty and provides a physiological explanation forhe difficulties faced by caregivers in deliveringhe dietary prescription.181,182 Gastroesophagealeflux was demonstrated in 73% of infants withhronic kidney failure, with poor feed intake andomiting183 and disordered gastric motility, de-ayed gastric emptying, and gastroesophagealeflux in 12 symptomatic children in associationith increased polypeptide hormone levels.184

Symptoms of vomiting, irritability, and discom-ort suggestive of gastroesophageal reflux ini-ially should be managed conservatively by con-entrating feeds to reduce feed volume andinimizing seated and supine positions after

eeds because there is some evidence of benefitn infants without CKD.185,186 Although therere no published data about the use of prokineticgents (eg, metoclopramide, a dopamine recep-or antagonist; domperidone, a peripheral D2

opamine receptor antagonist) or gastric aciduppressants (H2 receptor blockers or protonump inhibitors) in children with CKD, their useay be helpful. If symptoms persist, anatomic

bnormalities should be excluded radiologically,ut the role of routine pH studies and tests ofastric emptying in those with CKD is not estab-ished. A fundoplication may be indicated forntractable vomiting and can be performed aftergastrostomy is placed.When poor appetite and vomiting preclude a

utritionally adequate intake, tube feeding com-only is implemented. Although registry data

rom the North American Pediatric Renal Trans-lant Cooperative Study (NAPRTCS) for the usef supplemental tube feeds in children youngerhan 6 years at the start of dialysis therapyhowed no improvement in linear growth, fol-ow-up was for only a year and no information

as available for calorie intake.187 However, in m

ingle-center studies, tube feeding has beenhown to facilitate weight gain and growth. Sig-ificant weight gain and catch-up growth werechieved in 35 children with CKD stages 4 to 5nd age younger than 5 years if tube feeding wastarted before the age of 2 years. Loss of nutri-ion from vomiting is variable and hard to assess;owever, the improved weight gain observed inhis study over 2 years with enteral feeding andithout an increase in energy intake for age

uggests that vomiting can be reduced by slowelivery of feeds.18 In a large study of 101nfants presenting with CKD who were youngerhan 6 months and had a GFR less than 20L/min/1.73 m2 or CKD stage 5 within 2 years,

1% of the 81 survivors were tube fed andchieved a mean height SDS within the normalange by 1 year, with continued improvementhereafter.17 In 12 infants starting PD therapy atounger than 1 year and on PD therapy for ateast a year in association with enteral feeding,eight, weight, and occipital head circumferenceDS all improved significantly by 1 year, withontinuing improvement in weight and occipitalead circumference into the second year.188

oleman et al154 included older children in theirtudy of tube feeding using gastrostomy buttonsn 22 children (0.2 to 10.3 years old) on long-erm dialysis therapy. Although growth data didot distinguish between those starting gastros-omy feeding before (n � 16) or after the age of 5ears (n � 6), mean height and weight SDSncreased significantly by 18 months. Howeveramage et al,189 in a study of 15 children on PD

herapy and gastrostomy fed, subdivided growthutcome into those age younger than 2.5 yearsn � 8) and those older than 2.5 years (n � 7) at thetart of tube feeding. There was no further de-rease in height SDS in either group, with signifi-ant weight gain in both age groups by 12onths.189 Therefore, tube feeding should be

onsidered for infants and children younger thanyears who do not meet their EER orally despiteietary intervention and who are underweight orrowth retarded (weight or length/height � �1.88DS) or failing to achieve normal rates of weightain or growth. Although there are limited databout the use of tube feeding in children olderhan 3 years, this approach should be consideredn the individual child with intake inadequate to

aintain expected weight gain to prevent malnu-

trlgfqbig

caeirfsbatAictotta

ilwTaoetmafpoteytaattt

ow

imsk5psaamlpmsraprlnrsetiIomtocwbd(oeot

gmattc

Energy Requirements and Therapy S39

rition, which increases the risk of infection,educes stamina and cognition, and compromisesong-term survival.70 However, treatment withrowth hormone may be indicated if growthailure persists despite meeting nutritional re-uirements, particularly after early childhood,ecause there is currently minimal evidence thatmproved nutrition alone can facilitate catch-uprowth.The method of tube-feed delivery and feed

omposition will depend on age, the presence orbsence of vomiting, nutrient requirements, min-ral and electrolyte imbalances, and the assessedntake that can be achieved orally. Infants mayequire only boluses of the balance of theireeding after oral feeds (ie, top-up boluses), butome may need the full prescription to be giveny tube, which can then be delivered by pump asn overnight feed, with the rate adjusted asolerated with additional daytime boluses (seeppendix 4, Table 38 for information about

ntroducing and advancing enteral feeds). Olderhildren may benefit from having the majority ofheir feed overnight to encourage hunger andral intake during the day and so they can be freeo undertake normal daytime activities withouthe pressure to meet all their requirements whilet school or socializing.

Dello Strogolo et al168 reported persistent feed-ng dysfunction in 8 of 12 infants with a GFRess than 35 mL/min/1.73 m2 who were managedith nasogastric tube feeds for at least 9 months.herefore, it is important that tube-fed infantsnd children be encouraged to continue someral intake or have continued oral stimulation,g, sucking on a pacifier and/or positive non-hreatening contact with food. Other studies areore encouraging. In 5 infants on PD therapy

nd nasogastric feeding with persistent food re-usal, intensive behavior therapy by a multidisci-linary team enabled the infants to convert to fullral feeding.190 Although there are concerns thatube feeding will further reduce oral intake, Led-rmann et al18 showed in children aged 0 to 2ears that the percentage of energy derived fromhe tube feed did not change over 2 years despiten increase in the absolute energy intake withge, confirming improved oral intake. The long-erm outlook for normal feeding after transplan-ation is excellent, with reports of successful

ransitioning of almost all tube-fed children to t

ral diet and fluids within 10 months if childrenith significant comorbidity are excluded.169,191

Although the preferred method of tube feedings by means of gastrostomy, nasogastric tubesay be used long term or as a temporary mea-

ure, particularly for infants weighing less than 4g or infants/children presenting with CKD stageneeding immediate PD therapy. Repeated re-

lacement due to vomiting with subsequent aver-ive behavior and the psychosocial problemsssociated with the visibility of the tube areverted by the use of gastrostomies. Gastrosto-ies may be placed either percutaneously (radio-

ogically or endoscopically) or by using an openrocedure. Minor complications are well docu-ented for both approaches, particularly exit-

ite erythema and infections. Migration of theetention disk and enterocolic fistulae can presents significant late complications of percutaneouslacement, although the latter may be avoided byadiological placement because the bowel is out-ined with contrast. Gastrocutaneous fistulae mayeed surgical closure after gastrostomy buttonemoval. A percutaneously placed gastrostomyhould be replaced every 18 to 24 months byither the same size gastrostomy tube or, if therack is adequate, a button gastrostomy accord-ng to the child’s and family’s preference.192,193

deally, placement of a gastrostomy tube shouldccur before PD catheter placement. The place-ent of a percutaneous gastrostomy while on PD

herapy should be discouraged because the riskf severe peritonitis and PD failure is high;onversely, an open Stamm gastrostomy, initiallyith a catheter and subsequently replaced by autton device, can be performed safely in chil-ren on PD therapy with suitable precautionseg, antibiotic and antifungal coverage and timeff PD therapy after placement). There is novidence of an increased incidence of bacterialr fungal peritonitis with an established gastros-omy.155,194,195

A fundoplication may be performed with theastrostomy or after initial gastrostomy place-ent if severe vomiting persists despite medical

nd nutritional management, but temporary HDherapy may be required.155,196 A Stamm gastros-omy can be created at the same time as PDatheter placement without additional complica-

ions.154

srnp

sibrc“sAetssC

tomniipocoidnisrmtHttswiaawtpac

hcrH

nitto

iapa1npnoaptqAamnreomf

teiisstiqlojim

H

Recommendation 4S40

The use of gastrojejunal tubes has been de-cribed by Geary and Chait,110 but the expectededuction in vomiting was not observed and theeed for continuous feed delivery reduces theractical application.Other approaches may improve the nutritional

tatus. In adult maintenance HD patients, increas-ng dialysis frequency to 6 times/wk improvedoth biochemical markers and weight gain.197 Aecent report of increased growth velocity in 5hildren with intensified daily HD allowed afree” diet raises the possibility that nutritionaltatus improves with a higher dialysis dose.149

lthough the appetite stimulant megestrol ac-tate has been used in adults on HD therapy,198,199

here are significant side effects and no publishedtudies or case reports of the use of appetitetimulants or anabolic agents in children withKD.The 3½- to 4-hour HD session, which charac-

eristically occurs thrice weekly, may offer anpportune time to provide oral nutritional supple-entation, provided the patient is tolerant of the

utrient intake during the session. Although thiss a common practice in Europe, the experiencen many other centers has been less positive,rompting a philosophy against the allowance ofral intake during HD in adult and even pediatricenters alike.200-203 The most frequent adverseutcome noted when meals have been provideds hypotension, presumably the result of eitherecreased cardiac output secondary to splanch-ic sequestration of blood or through a decreasen splanchnic resistance leading to a reduction inystemic vascular resistance.204,205 A decrease inelative blood volume also has been docu-ented.206 However, more recently, a prospec-

ive study of 85 adults receiving maintenanceD revealed the nutritional benefit and patient

olerance of an oral supplement provided duringhe HD session.207 In a subsequent retrospectivetudy of 126 stable adult HD patients, there alsoas no evidence of an association between oral

ntake during HD and intradialytic hypotension,lthough the prescribed dry weight was notchieved in a substantial percentage of patientsith high oral intake.208 It is distinctly possible

hat the fewer comorbidities that characterizeediatric versus adult patients receiving HD aressociated with decreased risk of postprandial

omplications. However, evidence supporting this I

ypothesis is not yet available and mandateslose monitoring of vital signs in any patient whoeceives nutritional supplementation during anD session.4.4: A trial of IDPN to augment inadequate

utritional intake is suggested for malnour-shed children (BMI-for-height-age < 5th percen-ile) receiving maintenance HD who are unableo meet their nutritional requirements throughral and tube feeding. (C)Malnutrition, short stature, and low BMI are

ndependent risk factors for mortality in adultnd pediatric patients.49,70,209 Data from adultatients receiving maintenance HD show thatnorexia is an independent risk factor for death2 months later.210 Children receiving mainte-ance dialysis report high rates of depression,211

oor adjustment to diagnosis and lower socioeco-omic status,212 and lower health-related qualityf life213-215 than healthy controls and thereforere at risk of anorexia-induced malnutrition. Oneediatric center reports that psychosocial/malnu-rition-related causes account for the most fre-uent reason for HD patient hospitalization.58

dvanced CKD stages are often associated withnorexia and gastrointestinal disorders, whichay inhibit the ability to maintain adequate

utritional status through the oral and/or enteraloute. IDPN can be provided to augment inad-quate nutritional intake in a small select groupf children who are malnourished and unable toeet their requirements through oral and tube

eeding.Pilot pediatric data from small cohorts suggest

hat IDPN can be efficacious to augment inad-quate oral and/or enteral nutrition in malnour-shed children, leading to improvements in BMIn children with organic,58,59,216 but not psycho-ocial,59 causes of malnutrition. Optimal IDPNolution composition is unknown; however, aypical IDPN prescription contains amino acidsn amounts to meet estimated daily protein re-uirements, as well as dextrose and 20% or 30%ipid components to increase the caloric impactf the IDPN. Substrate infusion rates are ad-usted upward as tolerated to enhance caloricntake while preventing or managing hyperglyce-

ia and hyperlipidemia (Table 5).Although data assessing IDPN efficacy in adult

D patients have not shown a clear benefit of

DPN to reduce mortality,217,218 such data may

nno

eipmaIecTastpnI

aaei

iAimo

sfiIssipt

aripw

tbr

APDFk from p

P

C

F

Energy Requirements and Therapy S41

ot be applicable to children, for whom adequateutrition is requisite for normal growth and devel-pment.IDPN is administered continuously during the

ntire course of the HD treatment and should benfused in the venous limb of the HD circuit torevent clearance of amino acids and trace ele-ents. More than two-thirds of the infused amino

cids are retained, and the fluid used to deliverDPN is removed through ultrafiltration. Tracelement solutions can be added to provide zinc,opper, selenium, manganese, and chromium.able 6 lists the potential adverse events associ-ted with IDPN and a recommended monitoringchedule. Postinfusion hypoglycemia or symp-oms suggestive of refeeding syndrome (eg, hy-okalemia, hypophosphatemia, and hypomag-esemia) have been seen rarely in children onDPN therapy.

In the absence of pediatric criteria, discontinu-tion criteria for adults may provide guid-nce.217,219 Suggested criteria include clinicalvidence of improving nutrition as evidenced byncreased dry weight and an increase in oral

Table 5. Nutrient Content or Infusion Rates

Parameter/NutrientGoldstein 2002

(n � 3)

ge (y) 17-25rotein, g/kg/treatment 1.3extrose, mg/kg/min 5-9at, g/kg/h not reportedcal/kg/treatment not reported 11 kcal/kg

Table 6. Potential Adv

Component Adverse Occurrence(s)

rotein None

arbohydrate Hyperglycemia (�350 mg/dL) SeruhoHD

● Fir● We

ra● Sy

at Hyperlipidemia(50% rise in pre-HD TG level

between 2 treatments)Hypersensitivity (egg allergy)

● Seanlip

● Duofdo

first 30 m

ntake to meet energy and protein requirements.dditional criteria for discontinuation include no

mprovement in nutritional status after 4 to 6onths of IDPN or complications or intolerance

f IDPN therapy.219

IDPN provision can require substantial re-ources and should be used only when adequatenancial and personnel resources are available.DPN should not be promoted as a sole nutritionource; it should be used to augment otherources. If the combination of oral and/or enteralntake and IDPN is unable to meet energy androtein requirements, daily total or partial paren-eral nutrition is indicated.

4.5: A balance of calories from carbohydratend unsaturated fats within the physiologicalanges recommended as the AMDR of the DRIs suggested when prescribing oral, enteral, orarenteral energy supplementation to childrenith CKD stages 2 to 5 and 5D. (C)Fats, carbohydrates, and proteins can substi-

ute for one another to some extent to meet theody’s energy needs. Uneven distribution of calo-ies from each of the macronutrients may be

N Reported From Small Pediatric Cohorts

Orellana 2005(n � 9)

Krause 2002(n � 4)

17-26 4-181.3 0.5-1.55-9 18-46

�0.2-0.3 �0.2rotein � dextrose; not reported for lipids 27-53

ccurrences with IDPN

toring Schedule Response to Adverse Event

ose before HD, 1HD and at the end of

k of IDPNr change in dextrose

atic patient

● Decrease dextrose rate by 2mg/kg/min

● Add insulin to IDPN

levels before firstnd treatment using

e first administrationnous lipids, a test.5 mL/min for the

● Discontinue lipids

● Discontinue lipids

of IDP

erse O

Moni

m glucur into

st weeek afte

temptom

rum TGd secoidsring thintravese of 0

in of infusion.

aacCcCfilrltareeoapas

fdttcics

orrcicscH(aaddtdacHw

tcca

oadtrwsdpohtaC

p1fcmdrsroLiieirdlaost

tdb(tac

Recommendation 4S42

ssociated with inadequacy of certain nutrientsnd increased risk of such chronic diseases asoronary heart disease, obesity, and diabetes.ardiovascular disease (CVD) is the leadingause of morbidity and death in the pediatricKD population.220,221 Upper extremes of BMI-

or-age are associated with higher mortality ratesn children on dialysis therapy and decreasedong-term allograft survival and higher mortalityates in pediatric transplant patients. Althougharge-scale studies of risk-factor outcomes forhose with CVD have not been performed indults or children with CKD, the high mortalityate supports the need for risk-factor reductionarly in the course of CKD to reduce long-termxposure to cardiovascular insult and improveutcomes. To achieve the best risk reduction, itppears that dietary strategies should aim torevent or minimize increased triglyceride (TG)nd cholesterol levels and avoid conditions—uch as obesity—that contribute to dyslipidemia.

It often is necessary to supplement an infant’sormula or a child’s diet with fat and carbohy-rate to provide optimal calories, especially whenhe child is fluid restricted. In the general popula-ion, low or high proportions of calories fromarbohydrate or fat are associated with nutrientnadequacies (eg, fat-soluble vitamins) and/orhronic diseases, including heart disease, obe-ity, and diabetes.175

Macronutrients are related to heart disease andbesity in many ways. Excess energy intakeesults directly in obesity, which increases theisk of heart disease. High intake of dietaryholesterol, saturated fat, or trans fatty acids canncrease total and low-density lipoprotein (LDL)holesterol levels in the blood whereas monoun-aturated and polyunsaturated fatty acids a de-rease total and LDL blood cholesterol levels.igh intakes of n-3 polyunsaturated fatty acids

omega-3 fatty acids [n-3 FA], docosahexanoiccid [DHA], and eicosapentanoic acid [EPA])re associated with decreasing TG levels and aecreased risk of heart disease. High carbohy-rate (ie, simple sugars) and low fat intakes tendo increase plasma TG levels and decrease high-ensity lipoprotein (HDL) cholesterol levels, withcarbohydrate source of monosaccharides (espe-ially fructose) causing a more extreme effect.ypertriglyceridemia also has been associated

ith enhanced glucose uptake in children on PD a

herapy. Dietary fiber, particularly naturally oc-urring viscous fiber, reduces total and LDLholesterol levels, and high intakes have beenssociated with reduced rates of CVD.

As noted previously, CVD is the leading causef morbidity and mortality in children with CKD,ccounting for approximately 25% of totaleaths.220,221 These rates are 1,000 times higherhan the national pediatric cardiovascular deathate.220 CVD in children with CKD is associatedith traditional (dyslipidemia, hypertension, obe-

ity, physical inactivity, and genetics) and nontra-itional factors (uremia, uremia-related anemia,rothrombogenic factors, inflammation, fluidverload, left ventricular hypertrophy, increasedomocysteine levels, and vascular calcifica-ion).220 Children with CKD have been identifieds being in the highest risk category for pediatricVD.173

Dyslipidemia occurs relatively early in therogression of CKD (ie, GFR, 30 to 59 mL/min/.73 m2) and increases in prevalence as kidneyunction deteriorates.222 In children and adoles-ents on PD therapy, reported rates of dyslipide-ia range from 29% to 87%.223 Hypertriglyceri-

emia and hypercholesterolemia have beeneported in 90% and 69% of children with CKDtage 5, respectively.224 Dyslipidemia in pediat-ic CKD manifests primarily as increased levelsf serum TG, contained predominantly in veryDLs (VLDLs) of hepatic origin.225 This occurs

n combination with high levels of VLDL andntermediate-density lipoproteins (IDLs), low lev-ls of HDL particles, and normal or modestlyncreased levels of total and LDL choleste-ol.226,227 Sometimes referred to as atherogenicyslipidemia, the metabolic abnormalities under-ying it are complex.227 Hypertriglyceridemia isn independent contributor to the developmentf CVD228-232 and may also accelerate progres-ion of CKD to CKD stage 5, dialysis, andransplantation.233-235

Recommended ranges for a healthy distribu-ion of calories from protein, fat, and carbohy-rate for the general pediatric population haveeen established by the DRI.175 These AMDRTable 7) are based on evidence that consump-ion greater or less than these ranges may bessociated with nutrient inadequacy and in-reased risk of developing such chronic diseases

s coronary heart disease, obesity, diabetes, and/or

cdtfsrf

slricstc

sfadsm(5lcfatclllfoWomi

tafehted

dpctrlo

mcaaabfCtdAdpranr

CFP

apW

D

T

S

A

ap

Energy Requirements and Therapy S43

ancer. There is no information to suggest thatietary advice regarding macronutrient distribu-ion in children with CKD should be differentrom that in the general population; therefore, iteems prudent to maintain a distribution of calo-ies similar to that recommended by the AMDRor children with CKD stages 2 to 5 and 5D.

The DRI provide further recommendations forpecific types of carbohydrate and fat to avoid orimit for the purpose of chronic disease riskeduction (Table 8). Given the high risk of CVDn children with CKD, it is recommended thathildren and their caregivers be counseled to useources of unsaturated fat rather than saturated orrans fats and, as much as possible, to chooseomplex carbohydrates instead of simple sugars.

Calorically dense formulas frequently are pre-cribed for infants; however, there are no AMDRor those younger than 1 year. Therefore, whendvancing the caloric density of formula, theistribution of protein, fat, and carbohydratehould be kept consistent with the base for-ula,236 which must adhere to strict standards

7% to 12% protein, 40% to 54% fat, and 36% to6% carbohydrate; www.codexalimentarius.net;ast accessed March 30, 2008). Infants and younghildren need a somewhat greater proportion ofat in their diets to meet energy needs. Proteinnd electrolyte issues typically predict whetherhe energy density of an infant’s formula can beoncentrated (ie, more formula concentrate andess water) or increased by the addition of modu-ar components of carbohydrates (eg, powder oriquid forms of tasteless glucose polymers) and/orat (eg, ordinary oil used at home, emulsified oil,r medium-chain TG; Appendix 3, Table 36).hen uremia, hyperkalemia, hyperphosphatemia,

r formula osmolarity prevent concentrating for-ulas, additions of carbohydrate and/or fat are

Table 7. Acceptable MacronutrientDistribution Ranges

Macronutrient Children 1-3 y Children 4-18 y

arbohydrate 45%-65% 45%-65%at 30%-40% 25%-35%rotein 5%-20% 10%-30%

Source: Health Canada: http://www.hc-sc.gc.ca/fn-an/lt_formats/hpfb-dgpsa/pdf/nutrition/dri_tables-eng.pdf. Re-roduced with the permission of the Minister of Publicorks and Government Services Canada, 2008.

ndicated. Fat additions to formula should be in W

he form of heart-healthy unsaturated fats, suchs canola, olive, or corn oil. Providing enteraleedings containing glucose polymers and oilmulsions in a balanced profile of fat and carbo-ydrate to children with CKD managed conserva-ively (n � 5) or by using PD (n � 5) did notnhance hyperlipidemia compared with 37 chil-ren who were not tube fed.237

Children with CKD stages 2 to 5 and 5D andyslipidemia have been identified as a high-riskopulation for CVD.173 Table 9 lists more pre-ise recommendations for stricter lowering ofotal dietary fat, cholesterol, and trans and satu-ated fats directed to toddlers, children, and ado-escents with dyslipidemia and CKD stage 5, 5D,r a kidney transplant.The K/DOQI Dyslipidemia Guidelines’ recom-endations, endorsed by the K/DOQI Cardiovas-

ular Guidelines, recommend that the dietarynd lifestyle recommendations made for adultsre also appropriate for postpubertal children anddolescents with CKD (Table 11), but that prepu-ertal children should follow recommendationsrom the National Cholesterol Expert Panel inhildren and Adolescents (NCEP-C).238 Since

hen, a consensus statement on dietary recommen-ations for children and adolescents from themerican Heart Association (AHA),239 en-orsed by the American Academy of Pediatrics,rovides more current guidance than the NCEP-Cecommendations for working with children anddolescents with CKD (Tables 9 and 10), recog-izing that dietary modifications to increase calo-ies or restrict potassium and/or phosphorus in-

Table 8. Additional Recommendations on SpecificTypes of Fat and Carbohydrate

Macronutrient Recommendation

ietary cholesterol As low as possible while consuming anutritionally adequate diet

rans fatty acids As low as possible while consuming anutritionally adequate diet

aturated fattyacids

As low as possible while consuming anutritionally adequate diet

dded sugars Limit to a maximal intake of no morethan 25% of total energy

Source: Health Canada: http://www.hc-sc.gc.ca/fn-an/lt_formats/hpfb-dgpsa/pdf/nutrition/dri_tables-eng.pdf. Re-roduced with the permission of the Minister of Public

orks and Government Services Canada, 2008.

tc

otmppaIfimgdiet

tlawIo

nsf

go5

hrfpststrmie

crt

E

DDTSC

RUUIRULEER

Recommendation 4S44

ake make macronutrient modifications morehallenging to achieve.

The extent to which the macronutrient contentf the diet should be manipulated must considerhe child’s nutritional status and other dietaryineral and/or electrolyte restrictions. The first

riority for nutritional care is meeting energy,rotein, and micronutrient requirements tochieve optimal growth for individual children.f a child is well nourished, adding dietary modi-cations for dyslipidemia prevention or manage-ent can be safely undertaken. Studies of the

eneral pediatric population have shown thatietary fat restriction to 30% of total caloricntake is safe and, in particular, free of adverseffects on growth, development, or nutri-ion.240,241

Renal diet restrictions to control uremia (pro-ein) and mineral and electrolyte abnormalitiesimit the variety and palatability of the diet, anddditional (dyslipidemia) restrictions can be over-helming and may reduce caloric intake further.

n light of this, dietary intervention for treatmentf dyslipidemia is not recommended for under-

Table 9. Dietary Treatment Recommendations fand Kidn

Macronutrient Serum LDL-C �100 mg/dL

nergy

ietary fat �30% of caloriesietary cholesterol �200 mg/drans fatty acids Avoidaturated fatty acids �7% of caloriesarbohydrate

Source: Kavey et al.173

Table 10. Tips to Implement AHA Pediatric Dietary GCVD in Prep

educe added sugars, including sugar-sweetened drinks ase canola, soybean, corn, or safflower oils, or other unsatse fresh, frozen, and canned vegetables and fruits, and s

ntroduce and regularly serve fish as an entrée.emove the skin from poultry before eating.se only lean cuts of meat and reduced-fat meat products.imit high-calorie sauces such as Alfredo, cream sauces, cat whole-grain breads and cereals rather than refined proat more legumes (beans) and tofu in place of meat for somead food labels—especially for breads, breakfast cerealssalt/low-sugar alternatives.

Source: Gidding et al.239

ourished children with CKD220,223; however,uch simple changes as a switch to heart-healthyats can be implemented easily.

4.6: Dietary and lifestyle changes are sug-ested to achieve weight control in overweightr obese children with CKD stages 2 to 5 andD. (C)Childhood obesity is an international public

ealth problem reaching epidemic proportions. Aeview of data from the US Renal Data Systemor more than 1,900 pediatric dialysis or trans-lant patients showed that mortality rates wereignificantly higher at the upper and lower ex-remes of BMI-for-age.49 Pretransplantation obe-ity and increased BMI-for-age after transplanta-ion are associated with decreased long-termenal allograft survival.176 Prevention and treat-ent of obesity in patients with CKD is also

mportant to reduce the risk of hyperlipid-mia.242

A multiorganization scientific statement onardiovascular risk reduction in high-risk pediat-ic patients made the following recommenda-ions for high-risk children, including those with

ldren with Dyslipidemia and CKD Stages 5, 5D,nsplant

Serum TG �150 mg/dL

associated with excess weight, energy balance �activity recommendations for weight loss

Low

Low simple carbohydrate

es for Prevention or Treatment of Dyslipidemia andal Children

es.oils, in place of solid fats during food preparation.every meal; be careful with added sauces and sugar.

sauces, and hollandaise.

ees.repared foods—for content, and choose high-fiber, low-

or Chiey Tra

If

uidelinubert

nd juicuratederve at

heeseducts.

e entr, and p

Crprsma

olipsd

E

M

F

F

B

F

S

ip

Energy Requirements and Therapy S45

KD stages 5 and 5D and kidney transplantecipients with a BMI greater than the 95thercentile. Step 1 treatment: (a) age-appropriateeduced-calorie training for child and family; (b)pecific diet/weight follow-up every 4 to 6onths, repeated BMI calculation at 6 months;

Table 11. Dietary Modifications to Lower Serum C

Food Choices Choose

ggs (cholesterol �200 mg/d) ● Limit to 2 eggs per weewhites in place of 1 egcholesterol-free egg suregularly

eat, poultry, and alternatives ● Lean meat products, w● Poultry without skin● Fish, shellfish● Low-fat tofu; tempeh; s

productsish, shellfish ● Fish or shellfish, baked

without additional fat

ats and oils (saturated fat�7% total kcal) (total fat25%-35% total kcal)

● Unsaturated oils—safflcorn, soybean, cottonsolive, peanut

● Margarine—made fromabove, especially soft

● Salad dressings—madthe oils above

reads and grains (dietaryfiber goal of �20 g/d maybe difficult with fluidrestriction; focus onviscous/soluble fiber)

● Breads without toppingingredients

● Cereals: oat, wheat, co● Pasta, rice● Crackers—low-fat anim

unsalted soda crackersticks, melba toast

● Homemade breads marecommended fats and

ruits and vegetables ● Choices within CKD difresh, frozen, or low-soforms

weets (may be restricted indiabetics or presence ofhigh TG)

● Sweets: sugar, syrup,preserves, candy mad(hard candy)

● Frozen desserts: low-fsherbet, sorbet, fruit ic

● Cookies, cakes, and pegg whites or egg subrecommended fats; anfig and other fruit bar c

● Nondairy regular and ftoppings in moderation

Note: Diet decisions should be made in consultation wndividual medical and nutritional condition. Careful selectihosphorus, potassium, and sodium restrictions.Reprinted with permission.223

nd (c) activity counseling with a goal of 1 hour c

r more of active play per day and screen timeimited to 1 hour or less per day. Step 2 treatmentf follow-up BMI remains greater than the 95thercentile: weight-loss program referral plus con-ider referral for exercise testing and recommen-ations from exercise specialist appropriate for

terol and Triglycerides for Adolescents with CKD

Decrease

se 2 eggees

● Egg yolks and whole eggs (often hiddeningredients in cookies, cakes, desserts)

med of fat

tein

● High-fat meals (sausage, bacon, organmeats such as liver, sweetbreads, brain)

● Sandwich-style meals such as ham, “coldcuts,” processed meats

iled ● Avoid consuming bones of fish (sardines,anchovies, fish heads, etc) due tophosphorus content

sunflower,anola,

f the oilsid formsany of

● Hydrogenated and partially hydrogenatedfats

● Coconut, palm kernel, palm oil, coconutand coconut milk products

● Butter, lard, shortening sold in cans,bacon fat, stick margarine

● Dressing made with egg yolk, cheese,sour cream, or milk

eese

ltigrain

ckers,read

h

● Breads of high-fat content such ascroissants, flaky dinner rolls

● Granolas that contain coconut orhydrogenated fats

● High-fat crackers (more than 3 g of fatper serving on label)

● Commercially baked pastries and biscuits

meters inanned

● Fried fruits or vegetables or served withbutter or cream sauces; avocado

jam,ut fat

nonfat

e withord cake;

hipped

● Candy made with chocolate, cream,butter, frostings

● Ice cream and regular frozen desserts● Commercially baked cookies, cakes,

cream and regular pies● Commercially fried pastries such as

doughnuts● Whipped cream

ephrology dietitian to adapt food choices to the patient’sods within each category will be necessary to stay within

holes

k, or ug, or usbstitut

ell trim

oy pro

or bro

ower,eed, c

any oand lique from

s or ch

rn, mu

al cras and b

de witoils

et paradium c

honey,e witho

at andeies madstitutesgel fooookiesrozen w

ith a non of fo

ardiac status.173 Interventional strategies for

toh

F

igriacat

efpbmhlsfspifiaTdbcbflor

O

hnattmatolv

Cwrclp121Dadtnoo

t�sDmtmasdsh(marayse

FitcncsD

r

Recommendation 4S46

reatment of child and adolescent overweight andbesity in the non-CKD population45 may beelpful.

iber

The AI for total fiber is based on daily caloricntake, and for all children 1 year and older is 14/1,000 kcal/d. To normalize cholesterol levels andeduce the risk of cardiovascular heart disease, anncrease in soluble fiber intake is recommended asn addition to reductions in saturated fatty acid andholesterol intake.239,241 Fiber also can aid laxationnd promote satiety, which can reduce energy in-ake and the risk of overweight.

Dietary fiber is found in most fruits, veg-tables, legumes, and whole grains, which areoods restricted in low-potassium and low-hosphorus diets; therefore, meeting daily fi-er recommendations for healthy children isore challenging for children with CKD who

ave limited intake of these foods due toow-potassium and/or low-phosphorus diet re-trictions. Appendix 3, Table 37 lists someoods containing 1.9 g or greater of fiber pererving and includes their potassium and phos-horus content to guide advice about increas-ng fiber intake for individual children. High-ber foods with extremely high potassiumnd/or phosphorus content have been omitted.asteless mineral- and electrolyte-free pow-ered forms of fiber (eg, Unifiber®, Benefi-er®) are available to add to meals or drinks ifhildren are unable to meet their fiber intakey diet. High-fiber diets require additionaluid intake, which may not be possible forliguric or anuric patients with strict fluidestriction.

mega-3 FattyAcids (n-3 FA)

Approximately 75% of children with CKDave hypertriglyceridemia, for which there iso effective therapy. Both primary and second-ry prevention studies provide strong evidencehat consumption of fish and fish oils rich inhe n-3 FAs EPA and DHA reduce all-cause

ortality and various CVD outcomes indults.243,244 By far, the strongest most consis-ent evidence of the cardioprotective benefitsf n-3 FA is for the lowering of serum TGevels that is dose dependent and similar in

arious (adult) populations.244,245 Adults with t

KD who were treated with n-3 FA for 8eeks had significant decreases in TG levels

anging from 20% to 50% compared withontrols.246-248 Pediatric data for the TG-owering effect of n-3 FA are limited to severalre/post studies.249,250 Eighteen children (7 to8 years old) on dialysis therapy experienced a7% decrease in TG levels from 236 � 31 to71 � 21 mg/dL after 8 weeks of EPA plusHA supplementation.251 In a trial of n-3 FA

nd alternate-day prednisone on progression ofisease in children and young adults (age, 7.4o 39.7 years) with immunoglobulin A (IgA)ephropathy, a 17% decrease in TG level wasbserved after 2 years of therapy with 3.36 g/df EPA plus DHA.252

EPA and DHA can be synthesized in vivohrough the elongation and desaturation of-linolenic acid; however, this process occurslowly and is inefficient. Therefore, EPA andHA, found almost exclusively in fish andarine sources, must be provided in the diet;

he highest sources are fatty fish (eg, tuna,ackerel, trout, salmon, herring, sardines, and

nchovies).253 Adults on dialysis therapy con-ume fish in amounts far less than recommen-ations and have lower tissue EPA plus DHAtores compared with healthy people.254 Theigher mercury content of certain fatty fishshark, swordfish, marlin, orange roughy, kingackerel, escolar [snake mackerel], tilefish,

nd albacore or “white” tuna) has led variousegulatory bodies to issue recommendationsbout the maximum intake of these fish foroung children, who are considered to be moreusceptible than adults to the adverse healthffects of methylmercury.

Several safety concerns around the use of n-3A have been raised, including prolonged bleed-ng times, worsening glycemic control in pa-ients with diabetes, small increases in LDLholesterol levels, and environmental contami-ants in fish-oil products. Despite these con-erns, n-3 FAs have been found to be extremelyafe by both Health Canada and the US Food andrug Administration.At this time, there is insufficient evidence to

ecommend routine use of n-3 FAs to treat hyper-

riglyceridemia in children with CKD.

●

●

●

●

●

●

●

●

●

●

●

Energy Requirements and Therapy S47

COMPARISON TO OTHER GUIDELINES

CARI CKD Guidelines: similar suggestionsfor energy intake and tube feeding, but no firmguidelines.European Pediatric Peritoneal Dialysis Work-ing Group: similar recommendations for en-ergy intake for PD and enteral feeding pa-tients, but less detail.

LIMITATIONS

No controlled trials; mainly small observa-tional and interventional studies.Studies of IDPN have the following issuesthat plague most pediatric CKD studies: (1)small sample size, (2) single-center popula-tions, and (3) no control group or randomiza-tion scheme for comparison.The absence of prospective studies in thepediatric HD population on the intake of foodis a major limitation. Whereas studies of adultpatients are available, differences in the cardio-vascular status of children and adults withCKD and on dialysis therapy make it difficultto extrapolate the adult experience to children.The vast majority of research has focused onthe effects and management of undernutritionin children with CKD, and not overnutrition.There are no studies examining the effect ofvarying macronutrient content on serum mark-ers of dyslipidemia or long-term cardiovascu-

lar outcomes in children with CKD.

RESEARCH RECOMMENDATIONS

Determination of energy requirements at dif-ferent stages of CKD and with different meth-ods of kidney replacement therapy.The role of enteral feeding in the older childand adolescent in preventing the developmentof protein-energy wasting syndrome.Research should be directed to further delinea-tion of the role and dose of IDPN to treatand/or prevent malnutrition in specific pediat-ric HD populations, including those receivingmore frequent HD.Research should be conducted to evaluate thetolerance of pediatric HD patients to intradia-lytic oral nutritional supplementation. Thequantitative contribution of the dialysis-basednutrition to the daily caloric and protein intakeand its impact on overall patient well-beingalso should be assessed.Research should be conducted to better delin-eate:● the risks and benefits of treatments such as

n-3 FA/fish-oil supplementation and plantstanols in children with CKD and dyslipide-mia.

● the impact of dietary and lifestyle factorson managing overweight/obesity in chil-dren with CKD and whether weight manage-ment has an impact on progression of

kidney disease, morbidity, and mortality.

dgalobatpaptp

5

5

5

tiaw

apccltol

S

RECOMMENDATION 5: PROTEIN REQUIREMENTS AND THERAPY

wqR

trpctesnirtwhamplRw8sop

nttdtlaossbonhnlmtss

INTRODUCTION

The recommendation for protein intake in chil-ren with CKD has to consider maintenance ofrowth and an adequate nutritional status, butlso the intrinsic link of DPI and phosphorusoad. The growing evidence for a major impactf phosphorus overload on cardiovascular mor-idity in children and adults with CKD providesrationale to avoid excessive protein intake in

his population. At a given level of quantitativerotein intake, the phosphorus content and bio-vailability of the protein sources, the quality ofrotein, and the metabolic environment are impor-ant additional factors to consider in the dietaryrotein prescription.

.1 It is suggested to maintain dietary proteinintake at 100% to 140% of the DRI forideal body weight in children with CKDstage 3 and at 100% to 120% of the DRIin children with CKD stages 4 to 5. (C)

.2 In children with CKD stage 5D, it issuggested to maintain dietary protein in-take at 100% of the DRI for ideal bodyweight plus an allowance for dialytic pro-tein and amino acid losses. (C)

.3 The use of protein supplements to aug-ment inadequate oral and/or enteral pro-tein intake should be considered whenchildren with CKD stages 2 to 5 and 5Dare unable to meet their protein require-ments through food and fluids alone. (B)

RATIONALE

5.1: It is suggested to maintain dietary pro-ein intake at 100% to 140% of the DRI fordeal body weight in children with CKD stage 3nd at 100% to 120% of the DRI in childrenith CKD stages 4 to 5. (C)Progressive CKD is generally associated with

reduction in spontaneous dietary intake of bothrotein and energy. In a study comparing 50hildren with CKD stages 3 to 4 with healthyontrols, protein intake was found to be 33%ower and energy intake was 10% lower in pa-ients with CKD.255 However, whereas spontane-us energy intake tends to be critically low, eg,

ess than 80% to 85% of the RDA, DPI in those m

American Journal of Kidney D48

ith CKD is far in excess of the average re-uirements, typically 150% to 200% of theDA.9,255,256

The efficacy of low-protein diets in reducinghe rate of CKD progression has been assessed inandomized prospective trials in both adult andediatric patients. In the MDRD trial, no signifi-ant beneficial effect of decreasing DPI from 1.3o either 0.58 or 0.3 g/kg/d, supplemented withssential keto acids, could be demonstrated; subtleigns of a suboptimal nutritional status wereoted with these diets.257 In a pediatric trialnvolving 191 children with CKD stages 3 to 4, aeduction in protein intake aiming at 100% (0.8o 1.1 g/kg ideal body weight [defined as theeight at the same percentile as the child’seight percentile for the same age and sex]) andchieving 120% of the dietary intake recom-ended by WHO did not alter the rate of CKD

rogression compared with a cohort with adibitum protein intake (mean, 181% ofDA).256,258 The reduction in protein intake,ith maintenance of energy intake at greater than0% of the RDA in both groups, did not affecttatural growth, weight gain, body composition,r serum albumin levels within the observationeriod of 2 to 3 years.Hence, although there is no evidence for a

ephroprotective effect of dietary protein restric-ion, protein intake can be restricted safely to 0.8o 1.1 g/kg/d in children with CKD. Becauseietary protein restriction reduces the accumula-ion of nitrogenous waste products and facilitatesowering dietary phosphorus intake, it appearsppropriate to gradually lower DPI toward 100%f the DRI in children advancing from CKDtage 3 to stage 5. This should delay the onset ofigns and symptoms of uremia, although it shoulde noted that in the pediatric trial cited, the timef initiation of kidney replacement therapy wasot delayed significantly in the low-protein co-ort. Moreover, implementation and mainte-ance of a strict low-protein diet requires a majorifestyle change that may not be acceptable toany families. Hence, moderate protein restric-

ion aiming at 100% to 140% of the DRI in CKDtage 3 and 100% to 120% of the DRI in CKDtages 4 to 5 may be a reasonable compromise in

ost cases (Table 12).

iseases, Vol 53, No 3, Suppl 2 (March), 2009: pp S48-S52

samisiap

tiospbbmminnTpoiwtcwcycSeb

io

s1al

cg

ISDca

laadrdb

girmnslas

07141

pensat

Protein Requirements and Therapy S49

These protein recommendations refer to atable child and assume that energy intake isdequate (ie, it meets 100% of estimated require-ents). Inadequate caloric intake results in the

nefficient use of dietary protein as a calorieource, with increased generation of urea. Ensur-ng caloric needs are met is an important step inssessing protein requirements and modifyingrotein intake.Protein requirements may be increased in pa-

ients with proteinuria and during recovery fromntercurrent illness. Modification of protein rec-mmendations also may be necessary in obese ortunted children. Obese individuals have a greaterercentage of body fat, which is much less meta-olically active than lean mass. Therefore, it iselieved that basing protein (and energy) require-ents of obese individuals on their actual weightay overestimate requirements. Conversely, us-

ng ideal body weight for an obese person doesot take into account the increase in body proteineeded for structural support of extra fat tissue.herefore, a common practice is to estimaterotein requirements of obese individuals basedn an “adjusted” weight (ie, adjusted weight �deal weight for height � 25% � [actualeight � ideal weight], where 25% represents

he percentage of body fat tissue that is metaboli-ally active) rather than their actual bodyeight.259 This formula is based on physiologi-

al theory rather than scientific evidence. Inoung children (ie, age �3 years) or stuntedhildren (ie, length- or height-for-age � �1.88DS), protein requirements initially should bestimated by using chronological age, but may

Table 12. Recommended Dietary Protein I

AgeDRI

(g/kg/d)

Recommended forCKD Stage 3

(g/kg/d)(100%-140% DRI)

RecomCKD

((100%

-6 mo 1.5 1.5-2.1 1-12 mo 1.2 1.2-1.7 1-3 y 1.05 1.05-1.5 1.-13 y 0.95 0.95-1.35 0.4-18 y 0.85 0.85-1.2 0.

*DRI � 0.1 g/kg/d to compensate for dialytic losses.†DRI � 0.15-0.3 g/kg/d depending on patient age to com

e reestimated by using height age if there are t

ndications of inadequate protein intake (see Rec-mmendation 5.3).5.2: In children with CKD stage 5D, it is

uggested to maintain dietary protein intake at00% of the DRI for ideal body weight plus anllowance for dialytic protein and amino acidosses. (C)

Our recommendations for DPI in dialyzedhildren differ from previous adult and pediatricuidelines based on several lines of reasoning.First, the Food and Nutrition Board of the

nstitute of Medicine of the National Academy ofciences in 2002 replaced the RDA of 1989 withRI values for the intake of nutrients by Ameri-

ans and Canadians. For protein, the DRI valuesre lower than the RDA across all age groups.175

Second, previous recommendations for dia-yzed patients were based on the concept that inddition to replacements for dialytic amino acidnd protein losses, at least 0.3 to 0.4 g/kg ofietary protein should be added to the intakeecommended for healthy subjects.62 The evi-ence base for this notion is weak and primarilyased on adult literature.The widespread notion that dialysis induces

eneralized protein catabolism through general-zed protein degradation resulting from cytokineelease induced by exposure to bioincompatibleembranes (in HD) or dialysis fluids (in PD) has

ot been universally confirmed by metabolictudies. Net protein “catabolism” seems to beimited to the dialytic removal of amino acidsnd/or protein and a slightly reduced proteinynthesis during HD sessions. Whole-body pro-

n Children with CKD Stages 3 to 5 and 5D

DRI

d for4-5

DRI)Recommended for HD

(g/kg/d)*Recommended for PD

(g/kg/d)†

1.6 1.81.3 1.5

5 1.15 1.35 1.05 1.15 0.95 1.0

e for peritoneal losses.

ntake i

mendeStagesg/kg/d)-120%

.5-1.8

.2-1.505-1.295-1.185-1.0

ein breakdown is not increased.260

biaapeppPndcsbbbeppt

adaittwcrisiltcn

occ2Dvbwhaa

ltdddcsspwv

pmthpdlpad

ccslpoewtaTdifdmrpepaipPgp

Recommendation 5S50

Observational studies showing a correlationetween high protein intake and better outcomesn adult dialysis patients261,262 do not prove that

high-protein intake by itself stimulates tissuenabolism. Reviews of nitrogen-balance studieserformed in adult dialysis patients with differ-nt protein intakes56,263-270 conclude that HDatients are in neutral nitrogen balance with arotein intake as low as 0.75 to 0.87 g/kg/d, andD patients, with 0.9 to 1.0 g/kg/d. A singleitrogen-balance study has been performed inialyzed children.152 In 31 pediatric patients re-eiving automated PD, the investigators ob-erved a positive correlation between nitrogenalance and DPI and concluded that DPI shoulde at least 144% of RDA. However, nitrogenalance also positively correlated with total en-rgy intake, and no multivariate analysis waserformed to address whether energy intake,rotein intake, or both were independent effec-ors of nitrogen balance.

A single randomized prospective study indults271 and several trials in children have ad-ressed the effect of selectively increasing aminocid supply in patients on PD therapy. Despitencreases in amino acid and dietary protein in-ake, no significant beneficial effects on nutri-ional status and longitudinal growth in childrenere achieved by this intervention, whereas urea

oncentrations frequently increased.272-276 Theseesults are compatible with the interpretation thatt is not possible to induce tissue anabolism byelectively increasing protein and amino acidngestion except in subjects with subnormal base-ine protein intake. If more protein is ingestedhan needed for metabolic purposes, all the ex-ess is oxidized and results in accumulation ofitrogenous-containing end products.Third, although evidence for beneficial effects

f a high DPI is lacking, there is growing con-ern that it may even be harmful to dialyzedhildren. In a DXA study of body composition in0 children on long-term PD therapy and a meanPI of 144% of the RDA, protein intake in-ersely correlated with bone mineral density,one mineral content, and fat-free mass, and alsoith plasma bicarbonate level, suggesting that aigh protein intake may cause tissue catabolismnd bone loss through aggravating metabolic

cidosis.277 i

Finally, the most convincing argument forimiting DPI in dialyzed children is derived fromhe solid evidence for a key etiologic role ofietary phosphorus load in the pathogenesis ofialysis-associated calcifying arteriopathy in pe-iatric and adult patients. Several studies ofhildren and adults with childhood-onset CKDtage 5 have demonstrated correlations betweenerum phosphorus levels and cumulative phos-hate-binder requirements and arteriopathy,278-282

hich, in turn, is linked to the excessive cardio-ascular mortality of patients with CKD.283,284

There is a nearly linear relationship betweenrotein and phosphorus intake,285 which deter-ines a frequent association of high protein in

he diet with hyperphosphatemia.286 Whereasyperphosphatemia is a powerful independentredictor of mortality on dialysis therapy,287 evi-ence for any benefit from high-protein diets isacking.288 Hence, it appears mandatory to limitrotein intake to the safe levels known to ensuredequate growth and nutrition in healthy chil-ren.The adverse impact of hyperphosphatemia on

ardiovascular, bone, and endocrine function inhildren with CKD mandates the preferentialelection of protein sources that are relativelyow in phosphorus. The lowest amount of phos-horus in proportion to the quantity and qualityf protein comes from animal-flesh proteins (av-rage, 11 mg of phosphorus per 1 g of protein),hereas eggs, dairy products, legumes, and len-

ils have higher phosphorus-protein ratios (aver-ge, 20 mg of phosphorus per 1 g of protein;able 13). Complexity is added by the variableigestibility of dietary protein and bioavailabil-ty of dietary phosphorus. Protein digestibilityrom animal proteins is 95%, whereas proteinigestibility from plant proteins (85%) and mixedeals (85% to 95%) is lower. Whereas phospho-

us in animal meat is stored as organic phos-hates in intracellular compartments that areasily hydrolyzed and readily absorbed, 75% ofhosphorus in plants is in the form of phyticcid. Because humans do not express the degrad-ng enzyme phytase, the bioavailability of phos-horus from plant-derived food is very low.hosphorus availability from animal products isreater than 70%, whereas availability from plantroducts (50%) and mixed meals (50% to 70%)

s lower. Hence, despite their higher specific

ptpbhapbqsttoe

aadatelpcficpppm

itptaiHsncsrtpn

aacaloeausaalaoa

trpaat

7

pbaAmP

EMTELLNMS

ie

NDc

Protein Requirements and Therapy S51

hosphorus content, some plant sources of pro-ein may actually result in a lower rate of phos-horus uptake per mass of protein than meat-ased foods (see Appendix 3, Table 35).289 Ifealthy humans are administered an equivalentmount of either animal or plant protein, urinaryhosphorus excretion is higher with the meat-ased diet.290 Moreover, meat products are fre-uently “enhanced” by the addition of phosphatealts; these additions may markedly increase theotal phosphorus load. Hence, a mixed composi-ion of dietary protein with a strong contributionf vegetable protein rich in phytic acid should bencouraged.

Although dialyzed children require largermounts of protein per unit of body weight thandults to grow in size and lean body mass, thisemand is fully accounted for by the age-djusted pediatric DRI. Hence, the only addi-ional dietary protein requirement justified byvidence is the replacement of dialytic nitrogenosses. In those on long-term PD therapy, dailyeritoneal protein losses decrease with age acrosshildhood from an average of 0.28 g/kg in therst year of life to less than 0.1 g/kg in adoles-ents.292 Peritoneal amino acid losses add ap-roximately one-third to the nitrogen lost withrotein, resulting in an total additional dietaryrotein requirement ranging from 0.15 to 0.35

Table 13. Average Ratio of Phosphorus to ProteinContent in Various Protein-Rich Foods

Food Category

Ratio of mgPhosphorusto g Protein

Ratio Adjustedfor Digestion/Absorption

gg white 1.4 1eat 9 6ofu 12 7gg 14 10egumes 17 10entils 20 12uts 25 15ilk 29 21eeds 50 29

Note: Mathematical estimations based on protein digest-bility-corrected amino acid scores (PDCAA) and data onstimated phosphorus bioavailability.©1998, Vegetarian Diets in Renal Disease article inutrition Update, Vegetarian Nutrition DPG Newsletter;PG, a dietetic practice group of American Dietetic Asso-iation. Used with permission.291

g/kg, depending on patient age (see Table 12). v

Peritoneal permeability for protein shows largenterindividual variation, but appears to be rela-ively constant within subjects. Transperitonealrotein transport correlated with small-moleculeransport rates; the peritoneal transporter statuss assessed by using the PET provides somendication of the level of peritoneal protein losses.igh peritoneal transporters tend to have low

erum albumin levels; these patients may be ateed for increased dietary protein supply. Be-ause dialytic protein concentrations can be mea-ured easily, consideration should be given toegular monitoring of peritoneal protein excre-ion and individual adaptation of the dietaryrotein prescription according to actual perito-eal losses.Amino acid and protein losses during HD vary

ccording to dialyzer membrane characteristicsnd reuse. Losses have not been quantified inhildren. In adults, an average of 8 to 10 g ofmino acids and less than 1 to 3 g of protein areost per HD session.288,293,293a,293b On the basisf 3 HD sessions per week for a 70 kg adult, thisquates to 0.08 g/kg/day.† Assuming that dialyticmino acid losses are in linear relationship torea kinetics, children can be expected to haveimilar or slightly higher amino acid losses thandults. An added DPI of 0.1 g/kg/d should beppropriate to compensate for pediatric hemodia-ytic losses (see Table 12). Under all conditions,t least 50% of dietary protein intake should bef high biological value‡ to protect body proteinnd mimimize urea generation.

In patients undergoing intensified HD modali-ies, in particular, extended nocturnal HD, theemoval of nitrogenous waste products and phos-horus is almost doubled, frequently resulting inneed for phosphorus substitution.294 Appetite

nd spontaneous dietary energy and protein in-ake reportedly increase in these patients. The

† (13 g AA and protein �3 sessions) 7 days per week 0 kg � 0.08 g/kg/d.‡ protein containing the 9 essential amino acids in a

roportion similar to that required by humans has highiological value. When one or more essential amino acidsre scarce, the protein is said to have low biological value.nimal sources of protein (eg, meat, poultry, fish, eggs,ilk, cheese, yogurt) provide high biological value protein.rotein found in plants, legumes, grains, nuts, seeds and

egetables are of low biological value.

eaap

ltwsi

miCtfl

eossnaoauddbfpccLdb

cgAt

●

●

●

●

●

Recommendation 5S52

xcellent nitrogen and phosphorus clearanceschieved with intensified treatment schedulesnd the concomitantly increased amino acid lossesermit and require liberalization of DPI.These recommendations for DPI refer to dia-

yzed children in stable clinical condition. Pro-ein requirements may be increased in patientsith proteinuria, during and after peritonitis epi-

odes, and during recovery from intercurrentllness.

5.3: The use of protein supplements to aug-ent inadequate oral and/or enteral protein

ntake should be considered when children withKD stages 2 to 5 and 5D are unable to meet

heir protein requirements through food anduids alone. (B)Occasionally, protein intake may be inad-

quate in children with CKD because of an-rexia, chewing problems, or the need for verytringent phosphorus restriction. Suggestedigns of inadequate protein intake include ab-ormally low serum urea levels, an undesir-ble downward trend in nPCR for adolescentsn HD therapy (see Recommendation 1, nPCR),nd/or documentation of low protein intake bysing food records, food questionnaires, oriet recall. Powdered protein modules (Appen-ix 3; Table 36) can be added to expressedreast milk, infant formula, beverages, pureedoods, or other moist foods to boost theirrotein content, and minced or chopped meat,hicken, fish, egg, tofu, or skim milk powderan be added to soups, pasta, or casseroles.iquid protein-rich renal supplements (Appen-ix 3) can also be used orally or enterally tooost protein intake.

COMPARISON TOOTHER RECOMMENDATIONS

The CARI CKD Guidelines recommend thathildren have a protein intake equivalent to orreater than those recommended by the Food andgriculture Organization, WHO, and United Na-

ions University for healthy children.

LIMITATIONS

The assumption that restricting protein intakemay lower dietary phosphorus load and therebycontribute to better cardiovascular outcomesin children with CKD has not been substanti-ated by clinical trial evidence to date.The bioavailability of phosphorus in manyprotein-containing foods is unknown or highlyvariable. Moreover, the effects of selectingdietary protein sources according to phospho-rus content and bioavailability may be overrid-den by hidden phosphorus sources in pro-cessed foods.

RESEARCH RECOMMENDATIONS

Controlled prospective studies are required tocompare the long-term effects of differentlevels of DPI on growth, nutritional status,serum phosphorus levels, and cardiovascularmorphology and function in children withCKD stages 2 to 5 and on dialysis therapy.Phosphorus bioavailability studies in humansfor various dietary protein sources are neededto provide comprehensive evidence-basedidentification of preferred dietary proteinsources.In children on PD therapy, amino acid–containing dialysis solutions are availablethat permit the provision of nitrogen carrierswithout any phosphate load. Whereas theuse of 1 bag of amino acid fluid per day didnot consistently improve the nutritional sta-tus of children on CAPD therapy, recentshort-term studies have suggested an anabo-lizing effect of combined peritoneal admin-istration of glucose and amino acids inchildren and adults on automated PD (APD)therapy.295-297 This concept requires furtherexploration in long-term randomized clini-cal trials. Longitudinal growth and nutri-tional status, as well as indicators of PD

efficacy and safety, should be studied.

tclasea

6

6

6

orpavca

tCvcr

A

RECOMMENDATION 6: VITAMIN AND TRACE ELEMENT

REQUIREMENTS AND THERAPY

danhfd

prcba�itoapsttaitoio

twslfrcaodm

CeteRsb

INTRODUCTION

Patients with CKD and those on dialysisherapy are at risk of vitamin and mineral defi-iencies as a result of abnormal renal metabo-ism, inadequate intake/poor gastrointestinalbsorption, and dialysis-related losses. The provi-ion of adequate quantities of these nutrients isssential because of their importance to growthnd development in children.

.1 The provision of a dietary intake consist-ing of at least 100% of the DRI forthiamin (B1), riboflavin (B2), niacin (B3),pantothenic acid (B5), pyridoxine (B6),biotin (B8), cobalamin (B12), ascorbic acid(C), retinol (A), �-tocopherol (E), vitaminK, folic acid, copper, and zinc should beconsidered for children with CKD stages2 to 5 and 5D. (B)

.2 It is suggested that supplementation ofvitamins and trace elements be providedto children with CKD stages 2 to 5 ifdietary intake alone does not meet 100%of the DRI or if clinical evidence of adeficiency, possibly confirmed by lowblood levels of the vitamin or trace ele-ment, is present. (C)

.3 It is suggested that children with CKDstage 5D receive a water-soluble vitaminsupplement. (C)

RATIONALE

6.1: The provision of a dietary intake consistingf at least 100% of the DRI for thiamin (B1),iboflavin (B2), niacin (B3), pantothenic acid (B5),yridoxine (B6), biotin (B8), cobalamin (B12),scorbic acid (C), retinol (A), �-tocopherol (E),itamin K, folic acid, copper, and zinc should beonsidered for children with CKD stages 2 to 5nd 5D. (B)

Little information exists about the vitamin andrace element needs specific to children withKD and those on dialysis therapy. However, iniew of the important role of these nutrients asofactors in a number of metabolic reactions, and

ecognizing that achieving the DRI should re- i

merican Journal of Kidney Diseases, Vol 53, No 3, Suppl 2 (Marc

uce the risk of developing a condition that isssociated with the nutrient in question that has aegative functional outcome,298,299 the practiceas been to target 100% of the DRI as the goalor children with CKD stages 2 to 5 and onialysis therapy (Table 14).The B vitamins are essential for carbohydrate,

rotein, and fat metabolism; oxidation-reductioneactions; transamination and decarboxylation; gly-olysis; and blood formation. Most thiamin in theody is present as thiamin pyrophosphate, which iscoenzyme for the oxidative decarboxylation of-ketoacids. The metabolism of riboflavin result-

ng in functional flavoproteins is important becausehe flavoenzymes are important factors involved inxidation-reduction reactions that are necessary forvariety of metabolic pathways, including energyroduction. Pantothenic acid is necessary for theynthesis of such compounds as fatty acids, choles-erol, and steroid hormones and for energy extrac-ion during oxidation of amino acids. Pyridoxine iscoenzyme for nearly 100 enzymatic reactions and

s essential for gluconeogenesis and niacin forma-ion. Biotin has an important role in the metabolismf carbohydrates, fatty acids, and some amino ac-ds. Finally, cobalamin has a key role in the metab-lism of folic acid.

Ascorbic acid is involved in collagen synthesishrough its role as a reversible reducing agent,hereas retinol is necessary for normal night vi-

ion. �-Tocopherol is the main antioxidant in bio-ogical membranes and vitamin K is a coenzymeor the posttranslational carboxylation of glutamateesidues that ultimately influence the coagulationascade. Folic acid is required for DNA synthesis,nd copper functions as a cofactor in several physi-logically important enzymes, such as lysyl oxi-ase, elastase, ceruloplasmin, and superoxide dis-utase, as does zinc.The DRIs were established by the Standing

ommittee on the Scientific Evaluation of Di-tary Reference Intakes of the Food and Nutri-ion Board, Institute of Medicine, National Acad-my of Sciences, as an expansion of the periodicDA reports. Most studies examining vitamin

tatus in children and adults with CKD occurredefore the release of the DRI and hence report

ntake relative to the earlier RDA. The DRIs

h), 2009: pp S53-S60 S53

atbmmectk

vcacfit

sm

ttdeae(

j

triatmtrsouawtwcatvatmdhfofv

VVVVTRNVFVPBCSZ

w

Recommendation 6S54

pply to the apparently healthy general popula-ion and are based on nutrient balance studies,iochemical measurement of tissue saturation orolecular function, and extrapolation from ani-al studies. Unfortunately, only limited data

xist about the vitamin needs for infants andhildren, and there is no assurance that meetinghe DRI will meet the needs of patients withidney disease.6.2: It is suggested that supplementation of

itamins and trace elements be provided tohildren with CKD stages 2 to 5 if dietary intakelone does not meet 100% of the DRI or iflinical evidence of a deficiency, possibly con-rmed by low blood levels of the vitamin or

race element, is present. (C)6.3: It is suggested that children with CKD

tage 5D receive a water-soluble vitamin supple-ent. (C)Children with CKD and those on dialysis

herapy are at risk of alterations in vitamin andrace element levels or function as a result ofecreased intake secondary to anorexia or di-tary restrictions, increased degradation or clear-nce from blood, loss per dialysis, or interfer-nce with absorption, excretion, or metabolismTables 15 and 16).

Although limited, most data about the sub-

Table 14. Dietary Reference Intake: Recom

Infants0-6 mo

Infants7-12 mo

Child1-3

itamin A (�g/d) 400 500 300itamin C (mg/d) 40 50 15itamin E (mg/d) 4 5 6itamin K (�g/d) 2.0 2.5 30hiamin (mg/d) 0.2 0.3 0iboflavin (mg/d) 0.3 0.4 0iacin (mg/d; NE) 2* 4 6itamin B6 (mg/d) 0.1 0.3 0olate (�g/d) 65 80 150itamin B12 (�g/d) 0.4 0.5 0antothenic Acid (mg/d) 1.7 1.8 2iotin (�g/d) 5 6 8opper (�g/d) 200 220 340elenium (�g/d) 15 20 20inc (mg/d) 2 3 3

Note: RDAs are in bold type; Als are in ordinary type.Source: Health Canada: http://www.hc-sc.gc.ca/fn-an/a

ith the permission of the Minister of Public Works and Gov*As preformed niacin, not niacin equivalents (NE) for this

ect are derived from studies of adult popula- q

ions. Whereas studies conducted in childreneceiving dialysis have documented dietaryntake of most water-soluble vitamins, zinc,nd copper that has been less than the RDA,he combination of dietary intake and supple-ental intake has routinely met or exceeded

he RDA.300-303 In large part, this is due to thearity of a vitamin and mineral supplementpecifically formulated for infants and childrenn dialysis therapy and the resultant need tose one of the proprietary renal supplementsvailable.304-306 Caution should be exercisedhen using these supplements to not exceed

he UL for the contents of the preparationhen the intake of diet and supplement is

ombined (Tables 17 and 18). In older childrennd adolescents, daily vitamin supplementa-ion is feasible without providing excessiveitamin intake. For smaller dosing in infantsnd toddlers, less frequent dosing (eg, every 2o 3 days) or partial dosing (eg, half tablet)ay be required if a liquid product or easily

ivisible tablet is not available. Children withealthy appetites for a variety of nutritiousoods and children receiving the majority or allf their energy requirements from adult renalormulas generally meet 100% of the DRI foritamins and trace elements and may not re-

d Dietary Allowance and Adequate Intake

Children4-8 y

Males9-13 y

Males14-18 y

Females9-13 y

Females14-18 y

400 600 900 600 70025 45 75 45 657 11 15 11 15

55 60 75 60 750.6 0.9 1.2 0.9 1.00.6 0.9 1.3 0.9 1.08 12 16 12 140.6 1.0 1.3 1.0 1.2

200 300 400 300 4001.2 1.8 2.4 1.8 2.43 4 5 4 5

12 20 25 20 25440 700 890 700 89030 40 55 40 555 8 11 8 9

ats/hpfb-dgpsa/pdf/nutrition/dri_tables-eng.pdf. Reprintednt Services, Canada, 2008.oup.

mende

reny

.5

.5

.5

.9

lt_formernmeage gr

uire vitamin supplementation.

W

pt

ibaH

B

C

F

N

P

P

R

T

A

R

V

V

trics.

Vitamin and Trace Element Requirements and Therapy S55

ater-SolubleVitaminsThiamin (vitaminB1)Adult patients with CKD ingesting a low-

rotein diet have demonstrated borderline low

Table 15. Physiological E

Name Effects of Deficiency

iotin Seborrheic dermatitis, anorexia,nausea, pallor, alopecia, myalgiaparesthesias

yanocobalamin(vitamin B12)

Pemicious anemia; neurologicdeterioration, methyl-malonicacidemia

olacin group ofcompounds

Megaloblastic anemia, impaired ceimmunity, irritability, paranoidbehavior, neural tube defects inof pregnant women

iacin (vitamin B3) Pellagra, dementia, diarrhea, derm

antothenic acid Observed only with use of antagondepression, fatigue, hypotensionmuscle weakness, abdominal pa

yridoxine (vitamin B6) Irritability, depression, dermatitis,glossitis, cheilosis, peripheralneuritis; in infants, irritability,convulsions, microcytic anemia

iboflavin (vitamin B2) Photophobia, cheilosis, glossitis,corneal vascularization, poor gro

hiamin (vitamin B1) Beriberi: neuritis, edema, cardiacfailure, hoarseness, anorexia,restlessness, aphonia

scorbic acid (vitamin C) Osmotic diarrhea, bleeding gums,perifollicular hemorrhage, frankscurvy

etinol (vitamin A) Night blindness, xerophthalmia,keratomalacia, poor bone growthimpaired resistance to infection,follicular hyperkeratosis

itamin E Hemolytic anemia in premature infafat malabsorption causes deficiehyporeflexia, and spinocerebellaand retinal degeneration

itamin K Primary deficiency rare; hemorrhagmanifestations, possible effect obone mineral density

Used with permission of the American Academy of Pedia

hiamin levels.307 In 1 study of children receiv- n

ng dialysis, the spontaneous dietary intake waselow the RDA in 28 of 30 patients.301 Whereassubstantial quantity of thiamin is removed byD, little appears to be lost by the perito-

and Sources of Vitamins

Effects of Excess Food Sources

Unknown Liver, egg yolk, soybeans,milk, meat

Unknown Animal foods only: meat,fish, poultry, cheese,milk, eggs, vitamin B12-fortified soy milk

Masking of B12 deficiencysymptoms in patients withpemicious anemia notreceiving cyanocobalamin

Yeast, liver, leafy greenvegetables, oranges,cantaloupe, seeds,fortified breads andcereals (grains)

Flushing, pruritis, liverabnormalities,hyperuricemia, decreasedLDL and increased HDLcholesterol

Milk, eggs, poultry, meat,fish, whole grains,enriched cereal andgrains

Unknown Organ meats, yeast, eggyolk, fresh vegetables,whole grains, legumes

Neuropathy, photosensitivity Liver, meat, whole grains,legumes, potatoes

Unknown Meat, dairy products,eggs, greenvegetables, wholegrains, enriched breadsand cereals

Unknown Enriched cereals andbreads, lean pork,whole grains, legumes,in small amounts inmost nutritious foods

Massive doses predisposeto kidney stones; nausea,abdominal pain; reboundscurvy when massivedoses stopped

Papaya, citrus fruits,tomatoes, cabbage,potatoes, cantaloupe,strawberries

Hyperostosis,hepatomegaly, hepaticfibrosis, alopecia,increased cerebrospinalfluid pressure, hypercalcemia

Fortified milk, liver, egg,cheese, yellow fruitsand vegetables(carotenoid precursors)

Bleeding, impairedleukocyte function

Sardines, green and leafyvegetables, vegetableoils, wheat germ, wholegrains, butter, liver, eggyolk

Water-soluble analogs only:hyperbilirubinemia,hemolysis

Cow milk, green leafyvegetables, pork, liver

8

ffects

s,

llular

fetus

atitis

ists;,in

wth

,

nts;ncy;r

icn

29

eal route in patients receiving chronic PD

(dDbth(

qamtHprm

tfl

odrddolftdirv

Z

S

C

trics.29

VVVVTRNVFVPBCSZ

d

Recommendation 6S56

CPD).308,309 In most cases, the combination ofietary intake and daily supplement to equal theRI will prevent deficiency. Thiamin stores cane assessed indirectly by means of erythrocyteransketolase activity or directly by means ofigh-performance liquid chromatographyHPLC).310-312

Riboflavin (vitaminB2)

A low-protein diet may contain inadequateuantities of riboflavin,312 and both Pereira etl301 and Kriley and Warady300 have docu-ented spontaneous intake of riboflavin less

han the RDA in children receiving dialysis.owever, riboflavin deficiency is uncommon inatients being treated with HD or CPD and whoeceive a combined diet/supplement intake thateets or exceeds the DRI. Erythrocyte gluta-

Table 16. Physiological Effec

Name Effects of Deficiency

inc Anorexia, hypogeusia, retarded growth,delayed sexual maturation, impairedwound healing, skin lesions

F

elenium Cardiomyopathy, anemia, myositis Ir

opper Sideroblastic anemia, retarded growth,osteoporosis, neutropenia,decreased pigmentation

F

Used with permission of the American Academy of Pedia

Table 17. Dietary Reference In

Infants0-6 mo

Infants7-12 mo

itamin A (�g/d) 600 600itamin C (mg/d) ND NDitamin E (mg/d) ND NDitamin K (�g/d) ND NDhiamin (mg/d) ND NDiboflavin (mg/d) ND NDiacin (mg/d; NE) ND NDitamin B6 (mg/d) ND NDolate (�g/d) ND NDitamin B12 (�g/d) ND NDantothenic Acid (mg/d) ND NDiotin (�g/d) ND NDopper (�g/d) ND NDelenium (�g/d) 45 60inc (mg/d) 4 5

Abbreviation: ND, not determined.Source: Health Canada: http://www.hc-sc.gc.ca/fn-an/

uced with permission of the Minister of Public Works and Govern

hione reductase activity is used to evaluate ribo-avin status.312

Niacin (vitaminB3)

There are limited data about the niacin statusf patients with CKD, with or without the use ofialysis. The metabolic clearance of niacin isapid, and thus it is believed that losses intoialysate are likely to be low. Prior studies haveemonstrated the intake of niacin to be less thanr equivalent to the RDA in patients prescribed aow-protein diet.314 Whereas Pereira et al301

ound the spontaneous intake of niacin to be lesshan the RDA in 27 of 30 children receivingialysis, the combined dietary and supplementntake exceeded the RDA in all cases. Thus, it isecommended that the DRI for niacin be pro-ided per diet and/or supplement.

Sources of Trace Elements

Effects of Excess Food Sources

ic effects; may aggravatenal copper deficiency

Oysters, liver, meat, cheese,legumes, whole grains

of mucous membranes,, irritability, indigestion

Seafood, meat, whole grains

ic effects; Wilsone, liver dysfunction

Shellfish, meat, legumes,nuts, cheese

8

Tolerable Upper Intake Levels

n Children4-8 y

Males/Females9-13 y

Males/Females14-18 y

900 1,700 2,800650 1,200 1,800300 600 800

ND ND NDND ND NDND ND ND

15 20 3040 60 80

400 600 800ND ND NDND ND NDND ND ND

3,000 5,000 8,000150 280 400

12 23 34

mats/hpfb_dgpsa/pdf/nutrition/dri_tables-eng.pdf. Repro-

ts and

ew toxmargi

ritationpallor

ew toxdiseas

takes:

Childre1-3 y

600400200

NDNDND

1030

300NDNDND

1,000907

alt_for

ment Services, Canada, 2008.

otamhAlvm

iIwStitpWimf

dbdtmHd

VVVVVTRNVFVPBCZI

d

IHIPOCTTCE

Vitamin and Trace Element Requirements and Therapy S57

Pantothenicacid (vitaminB5)

There are few data available about the statusf pantothenic acid in adult patients with CKD orhose receiving dialysis, and no data are avail-ble for children. However, the vitamin is re-oved by HD, and normal, low, and high levels

ave been found in adult dialysis patients.315-317

ccordingly, patients on HD and CPD therapyikely should receive 100% of the DRI for thisitamin. Pantothenic acid levels are measured byeans of radioimmunoassay.

Pyridoxine (vitaminB6)

Low pyridoxine intake has been documentedn a number of adult surveys of dialysis patients.n children, low intake of pyridoxine in childrenith CKD was reported by Foreman et al.9

tockberger et al318 found intake to be lowerhan 59% of the RDA in 67% of children receiv-ng CPD, and Pereira et al301 noted intake lesshan the RDA in 26 of 30 pediatric dialysisatients. In a study of infants receiving CPD,arady et al303 documented dietary pyridoxine

ntake of only 60% RDA. There are also a host ofedicines that can interfere with pyridoxine (and

Table 18. Multiv

Nutrient

PaediatricDialyvit†

(per tablet)Ketovite‡

(per tablet)

Replavite &Hill-Vite

(per tablet)

itamin A (�g) — — —itamin C (mg) 40 17 100itamin D (�g) — — —itamin E (mg) 6 5 —itamin K (�g) 20 500 —hiamin (mg) 0.8 1 1.5iboflavin (mg) 1 1 1.7iacin (mg) 12 3.3 20itamin B6 (mg) 2 0.3 10olic Acid (�g) 1,000 250 1,000itamin B12 (�g) 1 — 6antothenic Acid (mg) 6 0.4 10iotin (�g) 20 170 300opper (�g) 800 — —inc (mg) 8 — —

ron (mg) — — —

*Representative but not all-inclusive list of vitamin prepar†Recommended dose for children 1-5 years old: half tab

aily.‡Recommended dose: 3 tablets daily.

olic acid) metabolism (Table 19).

Low blood levels (measured as plasma pyri-oxal-5-phosphate by means of HPLC) haveeen documented in HD and CPD patients, andialysis removal of the nutrient likely contributeso the deficiency. A daily pyridoxine-HCl supple-ent of 10 mg has been recommended for adultD and CPD patients because this is the lowestose that has been proved to correct pyridoxine

Comparisons*

800c 15let)

Nephrocap(per caplet)

Nephronex Caps(per caplet)

LiquidNephronex(per 5 mL)

Strovite ForteSyrup

(per 5 mL)

— — — 400100 60 60 100— — — 3.3— — — 6.7— — — —

5 1.5 1.5 1.5 57 1.7 1.7 1.7 5.7

20 20 20 33.310 10 10 6.7

1,000 1,000 900 3336 10 10 6.75 10 10 8.3

150 300 300 50— — — 1,000— — — 5— — — 3.3

y; Recommended dose for children � 5 years old: 1 tablet

Table 19. Medicines and Other SubstancesInterfering with Vitamin B6 and Folic Acid Metabolism

That May Contribute to Vitamin Deficiency

Vitamin B6 Folic Acid

soniazide Salicylazosulfapyridineydralazine Ethanol

pronlazide Diphenylhydantoinenicillamine Methotrexateral contraceptives Pyrimethamineycloserine Pentamidinehyroxine Trimethoprimheophylline Triamtereneaffeine Cycloserinethanol Mysoline

PrimidoneBarbituratesYeasts, beans

itamin

Dialyvitewith Zin(per tab

—60———1.1.

2010

8006

10300

—15—

ations.let dail

Reproduced with permission.308

dtstcthtncpf

lptpHbprawsPc

lagdraFbsmhdcmwacotc

sscibatanRotr

anteDtb

prsilftnroid1stcTsDsfl

Recommendation 6S58

eficiency. Lower supplemental doses, in addi-ion to that provided by diet, likely would beufficient in infants and young children based onhe marked increase in blood level that has oc-urred with a 10-mg supplement in this popula-ion.300 Supplements that equate to the RDAave previously been recommended.302,319 Func-ional tests (eg, erythrocyte oxaloacetate transami-ase) have been used to assess vitamin B6 defi-iency. As noted, direct measurement of totalyridoxine by means of HPLC also can be per-ormed.

Biotin (vitaminB8)

The intake of biotin has been estimated to beess than the RDA in adult patients with CKDrescribed with a low-protein diet.316 In addi-ion, intestinal absorption of biotin may be com-romised in patients with CKD. The impact ofD on biotin status is poorly understood becauseoth high and low blood levels have been re-orted.320,321 Although there is no informationegarding the influence of CPD on biotin lossesnd there is no information at all from childrenith kidney disorders, intake equal to the DRI

hould be provided per diet and/or supplement.lasma biotin is measured by using microbiologi-al assays.

Folic acid (vitaminB9)

Litwin et al321a documented normal folic acidevels in 18 children with CKD and Pereira etl301 found the dietary intake of folic acid to bereater than the RDA in 21 of 30 pediatricialysis patients. Low folic acid levels have beeneported in adult patients receiving CPD, with anverage dialysis loss of 107 �g/d in 1 study.322,323

olic acid status (red blood cell and plasma) maye compromised by inhibitors of folic acid ab-orption (Table 19). Folic acid (along with vita-ins B6 and B12) also has a key role in the

andling of plasma homocysteine. Whereas someata have suggested that increased plasma homo-ysteine levels are a risk factor for CVD, otherore recent studies have suggested other-ise.324,325 Studies conducted in children have

ll demonstrated lowering of the plasma homo-ysteine level (the normal plasma concentrationf homocysteine is �5 to 10 �mol/L) followinghe provision of folic acid.326-329 Thus, most

hildren with CKD and those on dialysis therapy m

hould receive the DRI, whereas adults are pre-cribed 1.0 mg/d.330,331 If lowering plasma homo-ysteine level is the clinical goal, children withncreased plasma homocysteine levels pro-ably should receive 2.5 to 5.0 mg/d of foliccid.305,310-313,315,317 However, in dialysis pa-ients, administration of folate and vitamins B6

nd B12 has been reported to lower, but notormalize, plasma homocysteine levels.332,333

ed blood cell folate levels are most indicativef body stores.334 The reduced form of folic acid,etrahydrofolate, may be measured by using aadioimmunologic technique.

Cobalamin (vitaminB12)

Most adult and pediatric patients with CKDnd dialysis patients have been reported to haveormal cobalamin levels, regardless of whetherhey receive a supplement.300,303,309,322,323 Di-tary intake also appears to meet or exceed theRI in most, but not all, dialysis pa-

ients.300,301,303,335 Serum vitamin B12 levels cane determined by using radioassay methods.

Ascorbicacid (vitaminC)

Decreased vitamin C levels have been re-orted in patients with CKD, as well as thoseeceiving HD and CPD.335-337 The low levelseen in dialysis patients are the result of lowntake (eg, restricted intake of fruits) and dialysisosses.301,322,335-337 In children, Pereira et al301

ound that 24 of 30 children received less thanhe RDA by diet alone. Warady et al303 reported aegative mass transfer of 32 mg/d in childreneceiving APD, an amount compensated for byral supplementation. However, in a study ofnfants receiving APD, Warady et al303 reportedietary intake to be 140% of RDA, increasing to80% of RDA with the addition of a 15-mg/dupplement. Excessive vitamin C intake (eg, 0.5o 1 g/d in adults) can result in increased oxalateoncentrations in plasma and soft tissues.338,339

hus, recommended combined dietary andupplement intake should not greatly exceed theRI, with caution exercised when providing

upplementation. Plasma ascorbic acid levels re-ect dietary intake, and leukocytes levels esti-

ate the body pool.

F

eCttlnriastgdsiwlPo

gptm

HhcaerrtC(vm

T

nA

mpdetlcs

tsrccatihCwSCniWmi

dRCDtc

●

●

Vitamin and Trace Element Requirements and Therapy S59

at-SolubleVitamins

Retinol (vitaminA)

Vitamin A is not removed by dialysis, andlevated serum levels are present in patients withKD and on dialysis therapy without supplemen-

ation.300,302,303,309 Whereas retinol-binding pro-ein (the transport protein for vitamin A) is catabo-ized in the renal tubules in individuals withormal kidney function, both vitamin A andetinol-binding protein accumulate when the GFRs reduced and there is impaired renal tubularctivity.340,341 Kriley and Warady300 documentederum vitamin A levels in pediatric dialysis pa-ients without supplements that were 3-foldreater than control patients. Because the risk ofeveloping vitamin A toxicity is high whenupplements with vitamin A are provided, totalntake of vitamin A should be limited to the DRI,ith supplementation rarely recommended and

imited to those with very low dietary intake.lasma vitamin A levels are measured by meansf HPLC.

VitaminK

There is no need for an intake of vitamin Kreater than the DRI unless the patient is eatingoorly and receiving long-term antibioticherapy.309,342,343 Plasma vitamin K levels areeasured by means of liquid chromatography.

�-Tocopherol (vitaminE)

Plasma vitamin E levels in patients receivingD have been reported as low, normal, andigh.344-346 No differences in levels were foundomparing predialysis and postdialysis samples,nd no �-tocopherol was found in dialysis efflu-nt.347,348 Studies of CPD patients have alsoeported both low and high levels of �-tocophe-ol.335,349,350 Nevertheless, because of its abilityo alleviate oxidative stress in patients at risk ofVD, patients with CKD and dialysis patients

aged � 9 years) should receive the DRI ofitamin E.351,352 Serum vitamin E levels areeasured by means of HPLC.

race Elements

Copper

Dietary intake less than the DRI has beenoted for copper in children receiving CPD.353

lthough copper excess is associated most com-

only with CKD, low serum copper and cerulo-lasmin levels also have been reported in chil-ren receiving HD.303 Intake should be monitoredvery 4 to 6 months because supplementation tohe DRI may be required in patients with particu-arly low dietary intake. Assessment of serumopper levels may be beneficial when clinicaligns of overload or deficiency are present.

Selenium

Although selenium is normally excreted byhe kidney and not removed by dialysis, lowerum levels occur in patients with CKD or thoseeceiving maintenance HD.337,354 The seleniumontent of food is dependent on the seleniumontent of soil on which crops have grown ornimals have grazed.309 Selenium-dependent glu-athione peroxidase activity in the blood, anntegral component of the antioxidant defense,as also been found to be lower in patients withKD than in healthy subjects, and the reductionorsens with increasing severity of disease.upplementation of selenium in patients withKD has resulted in a minimal increase in sele-ium-dependent glutathione peroxidase activityn patients with CKD, but not dialysis patients.

hereas routine supplementation is not recom-ended, patients should receive a daily dietary

ntake that meets the DRI.

Zinc

Low serum zinc levels result from removal byialysis and poor intake. Intake less than theDA has been documented in children receivingPD.353 Children and adults should receive theRI for zinc, with supplementation reserved for

reatment of clinical manifestations of zinc defi-iency after laboratory confirmation.

COMPARISON TO OTHER GUIDELINES

Vitamin and trace element intake recommen-dations are included in the European BestPractice Guideline on Nutrition.309 However,those guidelines address the needs of only theadult HD population.The pediatric portion of the CARI CKDGuidelines recommends supplements of water-soluble vitamins for dialysis patients not re-ceiving nutritional supplements. Supplements

of vitamins A, B12, and E are not recom-

●

avtorc

onb

●

●

●

●

Recommendation 6S60

mended because dietary intake routinely meetsthe DRI. The DRI for copper and zinc arerecommended, with regular monitoring ofserum zinc levels in patients receiving alow-protein diet.334

The European Pediatric Peritoneal DialysisWorking Group recommends vitamin and tracemineral intake in accordance with referencenutrient intake.319

LIMITATIONS

The absence of studies in children with CKDnd those on dialysis therapy that have assesseditamin and trace element blood levels (1) beforehe institution of supplementation or after a wash-ut period, and (2) after supplementation in aandomized manner with a control group for

omparison. In addition, of the limited number

f studies on the topic, most address dialysis andot predialysis patients with CKD, and all areased on single-center populations.

RESEARCH RECOMMENDATIONS

Assess the selenium status of children withCKD stages 2 to 5 and 5D,Assess the vitamin and trace element needs ofchildren with CKD and those on dialysistherapy by studying dietary intake and bloodlevels of these patients before and after supple-mentation,Assess the vitamin and trace element needs ofpatients receiving frequent HD,Further the development of a vitamin andtrace element formulation designed to specifi-

cally meet the needs of pediatric patients.

ciWdom

aattc

hcmeoaC(ctiaihbwctAr

vmapflme

A

RECOMMENDATION 7: BONE MINERAL AND VITAMIN D

REQUIREMENTS AND THERAPY

tsscsa

r(cnltc1yD

pariptpa

lCam

est

07149

7.1: Calcium

INTRODUCTION

The management of oral and/or enteral cal-ium intake in children with CKD is a challeng-ng problem for physicians and dietitians.

hereas insufficient calcium supply may causeeficient mineralization of the skeleton, calciumverload may be associated with severe vascularorbidity.7.1.1 In children with CKD stages 2 to 5

nd 5D, it is suggested that the total oralnd/or enteral calcium intake from nutri-ional sources and phosphate binders be inhe range of 100% to 200% of the DRI foralcium for age. (C)

RATIONALE

Adequate dietary calcium intake during child-ood is necessary for skeletal development, in-luding acquisition of an optimal peak boneass during puberty.355 Both insufficient and

xcessive oral and/or enteral calcium supply mayccur in children with CKD. Intestinal calciumbsorption is increasingly impaired in those withKD as endogenous production of calcitriol

1,25-dihydroxyvitamin D; 1,25[OH]2D) de-reases, but is readily stimulated by vitamin Dherapy. Spontaneous calcium intake frequentlys insufficient in adolescent patients in whomcceptance of high-calcium foods is limited andn children on phosphorus-restricted diets. Theomeostatic mechanisms for regulating calciumalance are impaired most severely in childrenith CKD stage 5 and on dialysis therapy. Cal-

ium absorption cannot be adjusted because ofhe kidney’s inability to produce 1,25(OH)2D.lso, vitamin D receptor expression may be

educed.However, therapy with high doses of active

itamin D sterols (eg, calcitriol, alfacalcidol)ay boost intestinal calcium absorption. Oral

nd/or enteral treatment with calcium-containinghosphate binders and absorption from dialysisuids with supraphysiological calcium contentarkedly enhance the calcium load. Increasing

vidence suggests that the resulting strongly posi- m

merican Journal of Kidney Diseases, Vol 53, No 3, Suppl 2 (Marc

ive calcium balance is a major contributor tooft-tissue calcifications. Although it is impos-ible to accurately assess the actual absorption ofalcium derived from diet and binders in thisetting, it appears reasonable to limit total oralnd/or enteral calcium ingestion.

Intake of 100% of the DRI for calcium is aeasonable starting point for children with CKDTable 20). Although the safe limit of dietaryalcium intake in children of different ages hasot been defined by study evidence, it appearsogical to scale maximal calcium intake relativeo the age-specific DRI. The safe UL of dietaryalcium intake in healthy individuals older thanyear is 2,500 mg/d. For adults and children 9

ears and older, this is approximately 2 times theRI.A number of measures are effective to im-

rove low oral and/or enteral calcium intake andbsorption: increased consumption of calcium-ich and/or calcium-fortified foods or tube feed-ngs, supplementation with calcium-containingharmacological agents between meals or bolusube feedings, use of calcium-containing phos-horus binders for managing hyperphosphatemia,nd supplementation with vitamin D.

If spontaneous intestinal calcium absorption isow, as typically observed in early stages ofKD, vitamin D should be supplemented tougment plasma 1,25(OH)2D synthesis and maxi-ize calcium absorption.If plasma calcium levels and urinary calcium

xcretion remain low and dietary assessmentuggests inadequate calcium intake, consump-ion of foods with high endogenous calcium

Table 20. Recommended Calcium Intake for Childrenwith CKD Stages 2 to 5 and 5D

Age DRI

Upper Limit(for healthy

children)

Upper Limit for CKD Stages2-5, 5D (Dietary �

Phosphate Binders*)

-6 mo 210 ND �420-12 mo 270 ND �540-3 y 500 2,500 �1,000-8 y 800 2,500 �1,600-18 y 1,300 2,500 �2,500

Abbreviation: ND, not determined.*Determined as 200% of the DRI, to a maximum of 2,500

g elemental calcium.

h), 2009: pp S61-S69 S61

cbfaurisbcvm

usctecoefada

btmbm

tpcitiamtitbDcbccd

C

C

C

C

Recommendation 7S62

ontent (eg, milk, yogurt, cheese, Chinese cab-age, kale, and broccoli) and calcium-fortifiedood products should be encouraged. The bio-vailability of calcium from milk and dairy prod-cts generally is high; however, the high phospho-us content of these products must be consideredn children who require dietary phosphorus re-triction. Some foods high in phytates, such asran cereal, may have poor bioavailability ofalcium.356-358 Fortified products seem to pro-ide calcium bioavailability comparable toilk.359-361

If dietary intake alone does not meet the DRI,se of oral and/or enteral calcium supplementshould be considered (Table 21). Salts of cal-ium—gluconate (9% elemental calcium), lac-ate (13% elemental calcium), acetate (25% el-mental calcium), or carbonate (40% elementalalcium)—are usually well tolerated by childrenf all ages. Calcium-containing phosphate bind-rs can be applied easily and effectively in in-ants. Conversely, calcium chloride should bevoided as a supplement in patients with CKDue to the possible development of metabolic

Table 21. Calcium Content of Commo

Compound Brand NameCo

alcium Acetate PhosLo™

alcium Carbonate Children’s MylantaChooz™ (Gum)TUMS™TUMS EX™ (extra strength)TUMS Ultra™LiquiCalCalciChew™CalciMix™Oscal 500™TUMS 500™Caltrate 600™NephroCalci™

alcium Citrate Citracal™

alcium Acetate �MagnesiumCarbonate

MagneBind™ 200 200c

450a

MagneBind™ 300c

300a

Adapted with permission.121

cidosis. Calcium citrate should not be given p

ecause citrate augments aluminum absorp-ion.362 Maximal absorption of calcium supple-

ents is achieved when calcium salts are takenetween meals and separate from iron supple-ents.363,364

As CKD progresses, increasing phosphate re-ention creates the need for oral and/or enteralhosphate-binder therapy. Calcium carbonate andalcium acetate are effective phosphate bindersn children and should be used as first-choiceherapy in patients with low dietary calciumntake.365-370 Calcium carbonate and calciumcetate easily can be crushed, dissolved in for-ula milk, and administered through enteral

ubes. However, hypercalcemic episodes occurn approximately 25% of patients, depending onhe type and dose of the calcium-containinginder and the coadministration of active vitamin

sterols (eg, calcitriol and alfacalcidol). Cal-ium acetate has a higher specific phosphorus-inding efficacy than calcium carbonate371 andauses fewer hypercalcemic episodes than cal-ium carbonate at a given phosphate-binderose.372-374 Hence, calcium carbonate should be

ium-Based Binders or Supplements

Content)

%Calcium

ElementalCalcium (mg)

No. of Pills to Equal�1,500 mg

Elemental Calcium

7 25% 167 9

0 40% 160 90 40% 200 7.5

0 40% 300 50 40% 400 3.750 40% 480 30 40% 500 3

0 40% 600 2.5

Not Recommended

esiumtem

(Magnesium� 57 mg)

113 mg

13

esiumtem

(Magnesium� 85 mg)

76 mg

20

n Calc

mpound(mg

66

4050

751,001,201,25

1,50

MagnarbonaCalciu

cetateMagn

arbonaCalciu

cetate

referred in children with insufficient dietary

ctamtcwbtehm

baesaittD4ct(cpcucum3a

atpfsctcdbtt

or

tpuiowitmHcadcccftdcbuwCndta

wfwoopetcim

●

●

Bone Mineral and Vitamin D Requirements and Therapy S63

alcium intake and no need for active vitamin Dherapy, whereas calcium acetate is the prefer-ble phosphate binder in children considered atoderate risk of calcium overload. In contrast to

he use of calcium salts as supplements, calcium-ontaining phosphate binders should be takenith meals to obtain maximal phosphorus-inding efficacy and minimal intestinal absorp-ion of free calcium. For calcium acetate, fecalxcretion of phosphate has been shown to beigher when the phosphate binder is given witheals.375

The use of any calcium-containing phosphateinder should be limited by the maximally accept-ble total oral and enteral calcium intake. Forxample, in a dialyzed 8-year-old with a typicalpontaneous dietary calcium intake of 700 mg/d,

maximum of 900 mg of elemental calciumngested as phosphate binders should be adminis-ered to stay within the recommended maximalotal calcium intake of 1,600 mg (200% of theRI). This would correspond to a prescription ofto 5 tablets containing 500 mg of calcium

arbonate (200 mg of elemental calcium) or 5ablets containing 667 mg of calcium acetate167 mg of elemental calcium) per day. If dietaryalcium intake is higher, calcium-containinghosphate-binder intake and/or dialysate cal-ium concentration need to be reduced, and these of calcium-free phosphate binders should beonsidered. In a 1-year-old anuric child with anpper limit of 750 mg/d of calcium intake, aaximum of 875 mg of calcium carbonate (ie,

50 mg of elemental calcium) per day would becceptable if dietary calcium intake is 400 mg.

These model calculations should be viewed asgeneral principle of dietary calcium prescrip-

ion and may not always be applicable in clinicalractice. Also, they do not consider confoundingactors, such as treatment with active vitamin Dterols, which has been found to increase cal-ium absorption (reported to be 35% to 40% inhose with CKD377) by 30%.378 The dosage ofalcium-based phosphate binders should be re-uced in dialysis patients with low PTH levelsecause these patients commonly have low-urnover bone disease with a reduced capacity ofhe bone to incorporate a calcium load.379

To avoid the critical accumulation of calcium,ligoanuric children on dialysis therapy may

equire a further reduction in total oral and en-

eral calcium intake from nutritional sources andhosphate binders. In those with CKD stage 5,rinary calcium excretion—the major physiolog-cal elimination pathway—is severely impairedr absent. An anuric child receiving HD or PDith a neutral dialysate calcium concentration is

ncapable of disposing of any calcium exceedinghe amounts required for bone formation by anyechanism other than soft-tissue precipitation.ence, the upper limit of dietary calcium intake

onsidered safe in healthy subjects may not bepplicable to oligoanuric patients. In these chil-ren, further limitation of oral and enteral cal-ium intake from both dietary sources and cal-ium-containing phosphate binders should beonsidered, although evidence to support thisurther restriction is not yet available. Modifica-ion to decrease the calcium concentration in theialysate is an additional therapeutic option to beonsidered in both HD and PD patients. Calciumalance during PD usually is negative with these of 2.5 mEq/L calcium dialysate and positiveith 3.0 to 3.5 mEq/L calcium dialysate.380-384

alcium balance during HD may be neutral oregative with the use of a 2.5-mEq/L calciumialysate.385,386 Dietary and pharmacological in-erventions should aim at avoiding both hypo-nd hypercalcemic episodes.

COMPARISON TO OTHER GUIDELINES

These recommendations are in agreementith the K/DOQI Clinical Practice Guidelines

or Bone Metabolism and Disease in Childrenith Chronic Kidney Disease in limiting totalral and enteral calcium intake to 200% or lessf the DRI. These guidelines differ in that theediatric K/DOQI Bone Metabolism and Dis-ase guidelines are more liberal and allow upo 2 times the DRI for elemental calcium byalcium-based phosphate binders and a totalntake of elemental calcium of up to 2,500g/d, regardless of age.

LIMITATIONS

Neither the lower nor the upper limits ofsafety for calcium intake have been deter-mined in children with different stages ofCKD or oligoanuria.The effect of concomitant treatment with

active vitamin D sterols on oral and enteral

●

●

●

●

la

7

7

7

7

mstfpTctvmptlvpntmhp

pwpalrijclCphsst

msl(aswa

Recommendation 7S64

calcium uptake is difficult to quantitate due tothe multiplicity of factors involved.Newer non–calcium-containing phosphorusbinders often are not available, and their costmay be prohibitive. Data for their safety ininfants and children are limited.

RESEARCH RECOMMENDATIONS

Short-term calcium balance studies and con-trolled long-term outcome studies are requiredin children receiving HD and PD to determinethe relative roles of dietary calcium, calcium-containing phosphate binders, and dialysatecalcium in the development of hypercalcemia,extraskeletal calcifications, CVD, adynamicbone disease, and bone fractures.Calcium balance between children with CKDwith and without oligoanuria should be com-pared.The long-term safety of non–calcium-contain-ing phosphate binders in infants and youngchildren requires further investigation.

7.2: Vitamin D

INTRODUCTION

Recent clinical evidence suggests a high preva-ence of vitamin D insufficiency in children anddults with CKD.

.2.1 In children with CKD stages 2 to 5 and5D, it is suggested that serum 25-hydroxyvitamin D levels be measuredonce per year. (C)

.2.2 If the serum level of 25-hydroxyvitaminD is less than 30 ng/mL (75 nmol/L),supplementation with vitamin D2 (ergo-calciferol) or vitamin D3 (cholecalcif-erol) is suggested. (C)

.2.3 In the repletion phase, it is suggestedthat serum levels of corrected total cal-cium and phosphorus be measured at 1month following initiation or change indose of vitamin D and at least every 3months thereafter. (C)

.2.4 When patients are replete with vita-min D, it is suggested to supplementvitamin D continuously and to moni-tor serum levels of 25-hydroxyvitamin

D yearly. (C) t

RATIONALE

A decrease in serum calcidol (25-hydroxyvita-in D; 25[OH]D), the substrate for renal synthe-

is of 1,25(OH)2D, induces secondary hyperpara-hyroidism in individuals with normal kidneyunction387,388 and may aggravate secondary hy-erparathyroidism in patients with CKD.389,390

he critical lower limit of the serum vitamin Doncentration is not well defined. Serum concen-rations show considerable seasonal and regionalariation. Although severe manifestations of vita-in D deficiency, such as osteomalacia and hy-

ocalcemia, are seen only with 25(OH)D concen-rations less than 5 ng/mL (�12 nmol/L), levelsess than 30 ng/mL (75 nmol/L) are suggestive ofitamin D “insufficiency” as manifested by hyper-arathyroidism and increased risk of bone demi-eralization and hip fractures.391,392 Supplemen-ation with vitamin D, 800 IU/d, along with aodest dietary calcium supplement, reduced the

ip fracture rate by 43% in a double-blindedlacebo-controlled trial in elderly women.393

Vitamin D insufficiency is observed in a largeroportion (typically 80% to 90%) of patientsith CKD.394,395 In a population-based study ofatients hospitalized in New England, CKD wasmajor risk factor for low serum 25(OH)D

evels.396 Vitamin D insufficiency may be moreelevant in those with CKD than in healthyndividuals because, in contrast to healthy sub-ects in whom 25(OH)D is not rate limiting foralcitriol synthesis,397 1,25(OH)2D levels corre-ated with 25(OH)D levels in patients withKD.394,395 This probably is explained by im-aired compensatory upregulation of renal 1-�-ydroxylase and an increased contribution oftrictly substrate-dependent extrarenal calcitriolynthesis in patients with impaired kidney func-ion.398,399

Reasons for the high prevalence of low vita-in D levels in patients with CKD include their

edentary lifestyle with reduced exposure to sun-ight, limited ingestion of foods rich in vitamin Dcod liver oil, fish, liver, egg yolk, fortified milk,nd fortified margarine), reduced endogenousynthesis of vitamin D3 in the skin in patientsith uremia,287 and urinary losses of 25(OH)D

nd vitamin D–binding protein in nephrotic pa-

ients.400

ovmaesrHctgebmpt

dc(CcpDcptigdwmlifc(

1tpvWbgw

am(aWmst

tpd

KM

rtns

●

�

5

1

Bone Mineral and Vitamin D Requirements and Therapy S65

Even in patients with CKD stage 5D with littler no residual renal 1-�-hydroxylase activity,itamin D deficiency is associated with morearked secondary hyperparathyroidism.401 In

nephric individuals, high doses of ergocalcif-rol (D2) or alfacalcidol (25[OH]D) can increaseerum calcitriol levels, pointing to a significantole of extrarenal 1-�-hydroxylase activity.402-404

owever, the role of 25(OH)D deficiency and itsorrection in patients on maintenance dialysisherapy is controversial because the ability toenerate adequate levels of 1,25(OH)2D is mark-dly reduced or absent. However, 25(OH)D haseen claimed to exert specific effects on celletabolism. 25(OH)D, but not 1,25(OH)2D, im-

roved muscular function and phosphate con-ent.405

In patients with CKD, nutritional vitamin Deficiency and insufficiency can be prevented ororrected by supplementation with vitamin D3

cholecalciferol) or vitamin D2 (ergocalciferol).holecalciferol appears to have higher bioeffi-acy than ergocalciferol, although long-term com-arative trials are lacking in humans.406,407 TheRI for prevention of vitamin D deficiency in

hildren and adolescents is 200 IU.376 This value,ublished more than a decade ago, is 50% lowerhan the RDA that it replaced and, given increas-ng reports of vitamin D insufficiency in theeneral public, is controversial. The requiredaily vitamin D intake for patients of any ageith CKD is unknown. In individuals with nor-al kidney function, the recommended upper

imit of vitamin D is 1,000 IU/d in neonates andnfants younger than 12 months and 2,000 IU/dor all other ages.376 The equivalent of this dosean be achieved by administering 1 capsule

Table 22. Recommended Supplementation for V

Serum 25(OH)D(ng/mL) Definition

5 Severe vitamin D deficiency

-15 Mild vitamin D deficiency

6-30 Vitamin D insufficiency

Note: Conversion factor for Serum 25(OH)D: ng/mL � 2.Adapted with permission.121

50,000 IU) once a month.408 Daily doses of

0,000 IU of ergocalciferol have been adminis-ered in adult patients with advanced CKD foreriods longer than 1 year with no evidence ofitamin D overload or renal toxicity.409,410

hereas signs of vitamin D intoxication woulde the exception at doses recommended in thisuideline, the development of hypercalcemiaould be evidence of excessive dosing.We recommend treating vitamin D deficiency

nd insufficiency, with the specific dosing regi-en dependent on the severity of the disorder

Table 22). Smaller doses of vitamin D probablyre sufficient in children younger than 1 year.hen repletion (ie, serum 25[OH]D � 30 ng/L) has been accomplished, vitamin D homeosta-

is should be maintained by once-daily adminis-ration of 200 to 1,000 IU.

Calcitriol, alfacalcidol, or other synthetic ac-ive vitamin D analogs (eg, doxercalciferol andaracalcitol) should not be used to treat 25(OH)Deficiency.

COMPARISON TO OTHER GUIDELINES

Our recommendations are in line with the/DOQI Clinical Practice Guidelines for Boneetabolism and Disease in Children with CKD.

LIMITATIONS

The doses of ergocalciferol or cholecalciferolequired to correct vitamin D insufficiency ando maintain normal vitamin D plasma levels haveot been established in children with differenttages of CKD.

RESEARCH RECOMMENDATIONS

The dose-response relationship, as well as the

D Deficiency/Insufficiency in Children with CKD

rgocalciferol (Vitamin D2) or Cholecalciferol(Vitamin D3) Dosing

Duration(mo)

000 IU/d orally or enterally � 4 wk or(50,000 IU/wk � 4 wk); then 4,000 IU/dor (50,000 IU twice per mo for 2 mo) �2 mo

3

000 IU/d orally or enterally � 12 wk or(50,000 IU every other wk, for 12 wk)

3

000 IU daily or (50,000 IU every 4 wk) 3

nmol/L.

itamin

E

8,

4,

2,

496 �

comparative safety and efficacy, of different

●

●

7

7

7

Capdl

lsgipeapas

nCipisipahibbtItgpetsmshc

mcogrtpltsmot

Recommendation 7S66

administration intervals (daily versus monthly)of equivalent total doses of ergocalciferol orcholecalciferol should be studied across pedi-atric age groups.The effects of ergocalciferol and cholecalcif-erol supplementation on serum 1,25(OH)2D,PTH, calcium, and phosphorus levels andbone and cardiovascular end points should bestudied in prospective controlled trials inchildren with different stages of CKD, includ-ing dialysis.The impact of various 25(OH)D treatmentregimens on bone health of children withCKD.

7.3: Phosphorus

.3.1 In children with CKD stages 3 to 5 and5D, reducing dietary phosphorus in-take to 100% of the DRI for age issuggested when the serum PTH con-centration is above the target rangefor CKD stage and the serum phospho-rus concentration is within the normalreference range for age. (C)

.3.2 In children with CKD stages 3 to 5 and5D, reducing dietary phosphorus in-take to 80% of the DRI for age issuggested when the serum PTH con-centration is above the target rangefor CKD stage and the serum phospho-rus concentration exceeds the normalreference range for age. (C)

.3.3 After initiation of dietary phosphorusrestriction, it is suggested that serumphosphorus concentration be monitoredat least every 3 months in children withCKD stages 3 to 4 and monthly inchildren with CKD stage 5 and 5D. (C)In all CKD stages, it is suggested toavoid serum phosphorus concentrationsboth above and below the normal refer-ence range for age. (C)

RATIONALE

Epidemiological studies of adult patients withKD have demonstrated a positive association,lbeit not a causal link, between hyperphos-hatemia and morbidity and mortality indepen-ent of CKD stage. Although the benefits of

owering serum phosphorus level on patient- a

evel clinical outcomes have not been demon-trated in prospective interventional studies, it isenerally accepted and biologically plausible thatncreased serum phosphorus levels be avoided inatients with CKD stages 3 to 5 and 5D in anffort to control CKD-associated bone diseasend CVD. Associations between hyperphos-hatemia and CKD-associated vasculopathy havelso been observed in children with CKDtage 5.282,411

Although serum phosphorus levels usually areot increased in the early stages of progressiveKD,363,412-414 the dietary phosphorus load is an

mportant determinant of the severity of hyper-arathyroidism, even in those with mild renalnsufficiency. In children and adults with CKDtage 3, dietary phosphorus restriction decreasesncreased PTH levels and increases 1,25(OH)2Droduction, whereas dietary phosphorus intakespproximately twice the DRI for age aggravateyperparathyroidism despite little or no changen serum phosphorus levels.413,415,416 Also, boneiopsy studies showed marked improvement inone resorption and defects in bone mineraliza-ion by using dietary phosphate restriction.415

n 4 studies in children, dietary phosphate res-riction did not lead to impaired staturalrowth.256,417-419 Studies in adult and pediatricatients provided no evidence for any adverseffect of dietary phosphate restriction on nutri-ional status.256,257,420-423 However, severe re-triction of dietary phosphorus in children withoderate and severe CKD leading to subnormal

erum phosphorus levels was associated withistological findings of worsening osteomala-ia.415

Hence, a solid body of evidence suggests thatoderate dietary phosphate restriction is benefi-

ial with respect to the prevention and treatmentf hyperparathyroidism and safe with respect torowth, nutrition, and bone mineralization. Weecommend limiting dietary phosphorus intakeo 100% of the DRI (Table 23) in normophos-hatemic patients (using/not using phosphorus-owering medications) if serum PTH concentra-ion exceeds the target range (Table 24). Althoughimilar PTH target ranges have been recom-ended by 2 Expert Work Groups,121,424 the

ptimal range is controversial and may be lowerhan previously believed.425 In CKD stages 4

nd 5, when serum phosphorus levels increase to

g(em

ciibpfitpsoCb

ipss

dpsp

dpuutpot

bipepc

btiSpu3

manmis

07149

apW

345

06161

0

m

Bone Mineral and Vitamin D Requirements and Therapy S67

reater than the target normal range for ageTable 25) and hyperparathyroidism is alreadystablished, phosphorus restriction to approxi-ately 80% of the DRI is recommended.Higher physiological serum concentrations of

alcium and phosphorus are observed in healthynfants and young children, presumably reflect-ng the increased requirements of these mineralsy the rapidly growing skeleton. Rickets due tohosphorus deficiency occurs in preterm infantsed insufficient amounts of phosphorus and innfants and children with hypophosphatemia dueo inherited disorders of renal phosphate trans-ort.426 Hence, when dietary phosphorus is re-tricted to control hyperphosphatemia and sec-ndary hyperparathyroidism in children withKD, subnormal serum phosphorus values shoulde avoided (Table 25).The dietary prescription should aim at minimiz-

ng phosphate intake while ensuring an adequaterotein intake. To achieve this aim, proteinources with low specific phosphorus contenthould be prescribed (see Table 13, Recommen-

Table 23. Recommended Maximum Oral and/orEnteral Phosphorus Intake for Children With CKD

Age DRI (mg/d)

Recommended PhosphorusIntake (mg/d)

High PTH andNormal

Phosphorus*

High PTH andHigh

Phosphorus†

-6 mo 100 �100 �80-12 mo 275 �275 �220-3 y 460 �460 �370-8 y 500 �500 �400-18 y 1,250 �1,250 �1,000

Source: Health Canada: http://www.hc-sc.gc.ca/fn-an/lt_formats/hpfb-dgpsa/pdf/nutrition/dri_tables-eng.pdf. Re-roduced with the permission of the Minister of Publicorks and Government Services Canada, 2008.*� 100% of the DRI.†� 80% of the DRI.

Table 24. Target Range of Serum PTH by Stageof CKD

CKD StageGFR Range

(mL/min/1.73m2)Target SerumPTH (pg/mL)

30-59 35-7015-29 70-110

, 5D �15 200-300

yReprinted with permission.121

ation 5). Most food sources exhibit good phos-hate bioavailability with the exception of planteeds (beans, peas, cereals, and nuts) that containhosphate in phytic acid.Milk and dairy products are a major source of

ietary phosphorus. In young infants with CKD,hosphorus control can be achieved easily bysing formulas with a low phosphorus content. Itsually is feasible, and common clinical practice,o continue oral and/or enteral use of a low-hosphorus formula and delay the introductionf phosphorus-rich cow’s milk until the age of 18o 36 months.

Dietary phosphate restriction can be hinderedy the inadvertent consumption of food contain-ng phosphate additives, which can increase phos-horus intake up to 2-fold compared with unproc-ssed foods. This is a particular problem inatients with CKD who rely heavily on pro-essed foods.427,428

Unfortunately, most available nutrient data-ases do not consider the impact of additives onotal phosphorus content of foods. An exceptions the USDA National Nutrient Database fortandard Reference, which lists more than 60hosphate-containing food additives (www.ars.sda.gov/Main/site_main.htm?modecode�12-5-45-00; last accessed October 23, 2008).The aspects mentioned illustrate that dietaryodification of phosphorus intake is a complex

nd challenging task. Multiple pitfalls, includingonadherence in older children and adolescents,ay result in inefficient lowering of phosphorus

ntake; conversely, overrestriction may lead toigns of phosphate deficiency, particularly in

Table 25. Age-Specific Normal Ranges of BloodIonized Calcium, Total Calcium and Phosphorus

AgeIonized

Calcium (mmol/L)Calcium(mg/dL)

Phosphorus(mg/dL)

-5 mo 1.22-1.40 8.7-11.3 5.2-8.4-12 mo 1.20-1.40 8.7-11.0 5.0-7.8-5 y 1.22-1.32 9.4-10.8 4.5-6.5-12 y 1.15-1.32 9.4-10.3 3.6-5.83-20 y 1.12-1.30 8.8-10.2 2.3-4.5

Adapted with permission121; Specker.524

Conversion factor for calcium and ionized calcium: mg/dL �.25 � mmol/L.Conversion factor for phosphorus: mg/dL � 0.323 �mol/L.

oung infants. Hence, involvement of an experi-

em

tppttltttl5sairbott

taliCremtfrGecsbdpsc

scscTbd

rtccclatcnwgPdedamfLiw

aptbbttp

oliIrdppb

msttgdm

Recommendation 7S68

nced pediatric dietitian is key to phosphorusanagement in children with CKD.A recent randomized clinical trial assessed

he efficacy of a low-phosphorus diet com-ared with additional treatment with differenthosphate binders in adults with CKD stages 3o 5. Coronary calcification increased in pa-ients on the low-phosphorus diet alone, to aesser extent in calcium carbonate-treated pa-ients, and not at all in sevelamer-treated pa-ients.429 Notably, urinary phosphorus excre-ion did not decrease by the institution of theow-phosphorus diet alone and increased by0% during the 2-year follow-up. These re-ults highlight the difficulty of implementingnd maintaining a phosphorus-restricted dietn clinical practice. Hence, dietary phosphateestriction should be considered an important,ut not solitary, component in the managementf uremic bone and vascular disease in associa-ion with vitamin D and phosphate-binderherapy and dialytic removal.

The link between hyperphosphatemia and pa-ient mortality observed in adult studies287,430-432

nd the associations between serum phosphorusevel and surrogate markers of vascular morbid-ty in adult and pediatric patients withKD282,433,434 provide a rationale to lower se-

um phosphorus levels pharmacologically if di-tary phosphorus restriction is insufficient toaintain normophosphatemia. The current goal

o target normal phosphorus levels is differentrom the allowance for slightly higher phospho-us values within the K/DOQI Pediatric Boneuidelines.121 Oral and enteral phosphate bind-

rs are effective in lowering serum phosphorusoncentrations in children with CKD.365-371 Ithould be noted that the association betweenone and mineral metabolism disorders and car-iovascular risk and mortality are largely re-orted from either in vitro or retrospective cohorttudies, which can prove association, but notause and effect.

If total intestinal calcium load becomes exces-ive or hypercalcemia exists with the use ofalcium-containing phosphate binders, thesehould be reduced in dose or replaced by cal-ium- and aluminium-free phosphate binders.he only calcium- and aluminum-free phosphateinder with proven efficacy and safety in chil-

ren is sevelamer, which has been assessed in 2 a

andomized controlled clinical trials studying aotal of 47 children. In 1 study, 29 hemodialyzedhildren were assigned to either sevelamer oralcium carbonate, and either calcitriol or doxer-alciferol, as well. Although serum phosphorusevels were equally well controlled in the sevel-mer and calcium-carbonate arms at the end ofhe 8-month study period, serum calcium andalcium-phosphorus ion product levels were sig-ificantly higher and hypercalcemia episodesere more frequent in the calcium-carbonateroup, with no significant difference in serumTH levels.435 The second trial used a crossoveresign to compare sevelamer with calcium ac-tate in 18 children with CKD stages 3 to 4 or 5During 8-week observation periods. Phosphorusnd PTH control were similar with both treat-ents, whereas hypercalcemia occurred more

requently with calcium acetate. A decrease inDL cholesterol levels by 34% and a greater

ncidence of metabolic acidosis were observedith sevelamer.436

Sevelamer is a resin that, in aqueous solution,ttains a gel-like consistency and cannot be ap-lied through feeding tubes without a high risk ofube blockage. However, it is possible to pretreatreast milk,437 infant formula, and cow’s milk438

y dissolving sevelamer, waiting for precipita-ion, decanting, and feeding the supernatant ofhe processed fluid. This maneuver reduces phos-horus content by 80% to 90%.Larger comparative trials in adults consistently

bserved lower serum calcium and higher PTHevels with sevelamer than with calcium-contain-ng phosphate binders.256,422,426-429,435-437,439-441

n adult patients with CKD stages 3 to 5 and 5D,andomized controlled trials have provided evi-ence that the use of sevelamer attenuates therogression of arterial calcifications compared withatients receiving calcium-based phosphateinders.429,439-441

Whereas neither cardiovascular nor all-causeortality was reduced significantly by using

evelamer therapy in 1,068 patients completinghe Dialysis Clinical Outcomes Revisited Study,he Renagel In New Dialysis Patients trial sug-ested a significant mortality reduction in inci-ent dialysis patients receiving sevelamer for aedian of 44 months.439,440

Lanthanum carbonate recently has become

vailable as an alternative calcium- and alumi-

naicdctama

bTcpctbipbdos

●

●

●

●

●

●

●

●

Bone Mineral and Vitamin D Requirements and Therapy S69

um-free binder with high affinity for phosphatend minimal intestinal absorption. In a random-zed study in adult patients, lanthanum carbonateontrolled plasma phosphate levels well and in-uced less adynamic bone disease than calciumarbonate.442 However, no long-term data abouthe effect of lanthanum on the functions of livernd kidney and bone, in which lanthanum accu-ulates,443 and its safety profile in children are

vailable.It should be emphasized that any phosphate-

inder therapy introduces a major pill burden.he need to swallow several large tablets orapsules with each meal is a major physical andsychological challenge to many patients thatan seriously compromise long-term adherenceo this and other medications. Hence, phosphate-inder therapy should be individualized, realiz-ng that in some patients, lowering of serumhosphate levels into the normal range may note possible or may lead to an unacceptableecreased quality of life. In these cases, otherptions, such as intensified dialysis protocols,hould be evaluated.

COMPARISON TO OTHER GUIDELINES

With respect to dietary phosphorus restriction,our guidelines are similar to the currentK/DOQI Pediatric Bone Guidelines121 by ourrecommendation to lower dietary phosphorusintake to 100% of the DRI in children with anincreased PTH level and normal serum phos-phorus level for age and to less than 80% ofthe DRI in children with both an increasedPTH level and increased serum phosphoruslevel for age.355 Furthermore, whereas theindication for calcium-free phosphate bindersis exclusively guided by serum calcium level,we also accept supramaximal total calciumintake as a reason to switch to calcium-freebinders irrespective of serum calcium level.Our goal to target normal phosphorus levels isdifferent from the allowance for slightly higherphosphorus values for children with CKDstages 5 and 5D within the K/DOQI Pediatric

Bone Guidelines.

The target PTH levels recommended here aresimilar to the European Guidelines for theprevention and treatment of renal osteodystro-phy in children with chronic renal failure,424

which recommend target PTH levels in thenormal range for children with CKD stages 1to 3 and 2 to 3 times normal for children withCKD stages 4 to 5 and 5D.

LIMITATIONS

Whereas dietary phosphate restriction andphosphate-binder therapy exert a beneficialeffect on secondary hyperparathyroidism, clini-cal trial evidence for an effect on such hardoutcome end points as mortality, arterial calci-fications, and hospitalization or fracture ratesis lacking.Both dietary phosphate restriction and the pillburden and side effects associated with oral orenteral phosphate-binder use can be bother-some and a challenge to long-term prescrip-tion adherence.

RESEARCH RECOMMENDATIONS

Randomized clinical trials are needed to as-sess the long-term impact of dietary phospho-rus restriction on biochemical parameters,bone mineral density, linear growth, nutri-tional status, preservation of kidney function,and cardiovascular function in children acrossthe age groups with CKD stages 2 to 4.Studies are needed to evaluate whether lower-ing serum phosphorus levels into the normalor low-normal range improves clinical out-comes in children with CKD stages 4 to 5 and5D, including assessments of coronary arterycalcification, intima-media thickness of largearteries, and arterial elasticity indices.Prospective comparative studies are needed toevaluate the efficacy and safety of differentphosphate binders, including lanthanum car-bonate, in children with CKD stages 4 to 5 and5D. Possible end points include biochemicalmarkers of bone and mineral metabolism,growth and nutritional status, and arterial

morphology and function.

vkttsaasspabw

sw

S

RECOMMENDATION 8: FLUID AND ELECTROLYTE REQUIREMENTS

AND THERAPY

ap

eiaamacudratdgedTssegvdnst

bscCsmpCbs2Nia1t

INTRODUCTION

Fluid and electrolyte requirements of indi-idual children vary according to their primaryidney disease, degree of residual kidney func-ion, and method of kidney replacementherapy. Supplementation or restriction of fluid,odium, and potassium intake is individualizednd influenced by the volume of urine outputnd the ability to concentrate urine, hydrationtatus, and the presence or absence of hyperten-ion or hyperkalemia. Dietary and other thera-eutic lifestyle modifications are recommendeds part of a comprehensive strategy to lowerlood pressure and reduce CVD risk in thoseith CKD.444

8.1 Supplemental free water and sodiumsupplements should be considered forchildren with CKD stages 2 to 5 and 5Dand polyuria to avoid chronic intravas-cular depletion and to promote optimalgrowth. (B)

8.2 Sodium supplements should be consid-ered for all infants with CKD stage 5D onPD therapy. (B)

8.3 Restriction of sodium intake should beconsidered for children with CKD stages2 to 5 and 5D who have hypertension(systolic and/or diastolic blood pressure> 95th percentile) or prehypertension(systolic and/or diastolic blood pressure> 90th percentile and < 95th percen-tile). (B)

8.4 Fluid intake should be restricted in chil-dren with CKD stages 3 to 5 and 5D whoare oligoanuric to prevent the complica-tions of fluid overload. (A)

8.5 Potassium intake should be limited forchildren with CKD stages 2 to 5 and 5Dwho have or are at risk of hyperkale-mia. (A)

RATIONALE

8.1: Supplemental free water and sodiumupplements should be considered for children

ith CKD stages 2 to 5 and 5D and polyuria to c

American Journal of Kidney D70

void chronic intravascular depletion and toromote optimal growth. (B)The primary cause of CKD needs to be consid-

red when initiating dietary modification of flu-ds and sodium. Although restriction of sodiumnd/or fluids is appropriate in children with CKDssociated with sodium and water retention, theost common causes of CKD in children are

ssociated with excessive loss of sodium andhloride. Infants and children with obstructiveropathy or renal dysplasia have polyuria, poly-ypsia, and difficulty conserving sodium chlo-ide. These children develop a salt-wasting statend require salt supplementation.119 In additiono its effect on extracellular volume, sodiumepletion also adversely affects growth and nitro-en retention.445 Sodium intake supports normalxpansion of the ECF volume needed for muscleevelopment and mineralization of bone.446

herefore, infants and children with polyuricalt-wasting forms of CKD who do not have theirodium and water losses corrected may experi-nce vomiting, constipation, and significantrowth retardation associated with chronic intra-ascular volume depletion and a negative so-ium balance.111 It is important to note thatormal serum sodium levels do not rule outodium depletion and the need for supplementa-ion.

Individualized therapy can be accomplishedy first prescribing at least the age-related DRI ofodium and chloride (Table 26).119 In 2 smallohort studies, infants with polyuric salt-wastingKD stages 3 to 5 who were given nutritional

upport with generous fluids and sodium supple-ents achieved better growth compared with

ublished data for nonsupplemented infants withKD. The dosage of sodium supplements usedy the 2 studies varied between 2 to 4 mmol ofodium (Na)/100 mL formula added to 180 to40 mL/kg/d of formula111 and 1 to 5 mmola/kg body weight/d120 and was adjusted accord-

ng to blood biochemistry test results. The aver-ge dose used in the first study was Na, 3.2 �.04 mmol/kg.111 Nasogastric or gastrostomyube feedings were used111 or suggested for criti-

al periods.120

iseases, Vol 53, No 3, Suppl 2 (March), 2009: pp S70-S74

ca

mmt

et

suwopmm8inTcmddeceat

cadp

pt

uitcdttstlsseha

dtdotsbicd

saasa

071491

d

lt � 2,

Fluid and Electrolyte Requirements and Therapy S71

Sodium given as alkali therapy should beonsidered as part of the daily sodium allow-nce.119

Home preparation of sodium chloride supple-ents using table salt generally is not recom-ended due to potential errors in formulation

hat could result in hypo- or hypernatremia.447

8.2: Sodium supplements should be consid-red for all infants with CKD stage 5D on PDherapy. (B)

Infants on PD therapy are predisposed to sub-tantial sodium losses, even when anuric. Highltrafiltration requirements per kilogram of bodyeight result in removal of significant amountsf sodium chloride. These losses cannot be re-laced through the low sodium content of breastilk (160 mg/L or 7 mmol/L) or standard com-ercial infant formulas (160 to 185 mg/L or 7 tommol/L).449 Consequences of hyponatremia

nclude cerebral edema and blindness; therefore,eutral sodium balance must be maintained.herapy should be individualized based on clini-al symptoms, including hypotension, hyponatre-ia, and/or abnormal serum chloride levels. So-

ium balance measurements, determined fromietary and medication intake and dialysate efflu-nt losses, should be considered every 6 monthsoncurrent with the measurement of dialysis ad-quacy. More frequent measurement is indicatedfter significant changes to the dialysis prescrip-ion or clinical status.

8.3: Restriction of sodium intake should beonsidered for children with CKD stages 2 to 5nd 5D who have hypertension (systolic and/oriastolic blood pressure > 95th percentile) or

Table 26. DRI for Healthy Children fo

Age

Total Water* (L/d) Sodium† (mg/

AI Upper Limit AI Uppe

-6 mo 0.7 ND 120 N-12 mo 0.8 ND 370 N-3 y 1.3 ND 1,000 1,-8 y 1.7 ND 1,200 1,-13 y 2.4 ND 1,500 2,4-18 y 3.3 ND 1,500 2,

Abbreviation: ND, not determined.Source: Health Canada: http://www.hc-sc.gc.ca/fn-an

uced with the permission of the Minister of Public Works a*Total water includes drinking water, water in beverages,†Grams of sodium � 2.53 � grams of salt; 1 teaspoon sa

rehypertension (systolic and/or diastolic blood o

ressure > 90th percentile and < 95th percen-ile). (B)

When kidney function is impaired, ECF vol-me increases, edema occurs, and blood pressurencreases. Hypertension is already common inhe early stages of CKD, with 48% to 63% ofhildren affected.444,450 More than 50% of chil-ren on dialysis therapy have uncontrolled hyper-ension,450,451 and an additional 20% have con-rolled hypertension.63,451-454 Children withevere hypertension are at increased risk of hyper-ensive encephalopathy, seizures, cerebrovascu-ar events, and congestive heart failure.455 Lessevere hypertension can contribute to progres-ion of CKD. Therefore, dietary modification isncouraged for children and adolescents whoave blood pressures in the prehypertensive range,s well as those with hypertension.455

A systematic review of pediatric clinical trialsemonstrated that modest dietary sodium restric-ion reduces blood pressure in hypertensive chil-ren without CKD.456 In dialysis patients, manybservational and interventional studies of pa-ients with CKD have shown that restrictingodium intake is an essential tool for volume andlood pressure control.457-459 Aside from prevent-ng acute complications of hypertension, optimalontrol of blood pressure reduces further kidneyamage and modifies progression of disease.The K/DOQI Clinical Guidelines for Hyperten-

ion,444 CVD,220 and Dialysis Adequacy63 arell in agreement that dietary sodium restriction isn important component of a comprehensivetrategy for volume and blood pressure control indults and children with CKD. The earliest rec-

r, Sodium, Chloride and Potassium

Chloride (mg/d) Potassium (mg/d)

AI Upper Limit AI Upper Limit

180 ND 400 ND570 ND 700 ND

1,500 2,300 3,000 ND1,900 2,900 3,800 ND2,300 3,400 4,500 ND2,300 3,600 4,700 ND

mats/hpfb-dgpsa/pdf/nutrition/dri_tables-eng.pdf. Repro-ernment Services Canada, 2008.

ater that is part of food.300 mg sodium.

r Wate

d)

r Limit

DD

500900200300

/alt_fornd Govand w

mmendation from the Hypertension Guidelines

w2Clmmcvatpf6smah

cndmw4amah1“abc

faaiaepa4s

bfstso

lpFcn1scacam

ab((Wsss

cpKdPtdssfm

doo

ttsHidrff

(a

Recommendation 8S72

as to limit daily sodium intake to less than,400 mg (�104 mmol).444 The more recentardiovascular and Adequacy Guidelines have

owered the recommendation to less than 2,000g (�87 mmol) of sodium per day.450,459 Theost recent 2005 Dietary Guidelines for Ameri-

ans older than 2 years460 recommend that indi-iduals with hypertension, blacks, and middle-ged and older adults aim to consume no morehan 1,500 mg (65 mmol) of sodium per day. Torovide more size-appropriate guidelines for in-ants and young children, based on a standard0- to 70-kg adult, 1,500 to 2,400 mg/d ofodium would be the equivalent of sodium, 1 to 2mol/kg/d. This degree of restriction is reason-

bly consistent with the age-appropriate DRI forealthy children (Table 26).The average daily intake of sodium in healthy

hildren is far above recommended levels. In aational community health survey, 77% of chil-ren aged 1 to 3 years exceeded the recom-ended upper limit for sodium (1,500 mg/d),ith a mean intake of 1,918 mg/d.461 In childrento 8 years old, daily intake averaged 2,700 mg

nd 93% had consumed more than the recom-ended upper limit. For most of these children,

dding salt at the table did not contribute to theirigh sodium intakes because 69% of those agedto 3 years and 52% of those aged 4 to 8 years

never” added salt to their food. Salt intakes ofdolescents exceeded recommended upper limitsy 27% to 79%; the intake of males was signifi-antly higher than that of females.

Sodium occurring naturally in food accountsor only about 10% of total intake, whereas saltdded at the table or while cooking providesnother 5% to 10% of total intake.462 The major-ty (75%) of sodium in the diet comes from saltdded by manufacturers during processing 462 tonhance flavor, control the growth of bacteria,rovide certain functional characteristics, or acts a preservative. By weight, salt is composed of0% sodium and 60% chloride. One teaspoon ofalt contains about 2,300 mg of sodium.

Reduction of sodium intake can be achievedy replacing processed and canned foods withresh foods; reading food labels to identify lessalty foods; reducing salt added to foods at theable; in cooking, substituting fresh herbs andpices to flavor foods; and eating fast foods less

ften. The nutrition facts panel on food labels t

ists sodium content as actual amount (mg) andercent of the recommended daily value (% DV).oods containing less than 140 mg or 5% DV areonsidered low in sodium,460 and foods that haveo more than 170 to 280 mg of sodium or 6% to0% of the DV for sodium should be chosen. Saltubstitutes, also referred to as light salts, typi-ally replace all or some of the sodium withnother mineral. Salt substitutes replacing Nahloride (NaCl) with potassium chloride (KCl)re contraindicated in children with hyperkale-ia.Certain medications (eg, antacids, laxatives,

nd nonsteroidal anti-inflammatory drugs) cane a significant source of sodium. Kayexalate®

sodium polystyrene sulfonate) contains 100 mg4.3 mmol) of sodium per 100 g of powder.

here available, non–sodium-containing potas-ium binders (eg, calcium polystyrene sulfonate)hould be used for children with severe hyperten-ion and hyperkalemia.

Restriction of salt and fluid intake requiresonsiderable patient motivation, which is often aroblem in the adolescent population. The/DOQI Hypertension Guidelines recommendietary education by a dietitian every 3 months.444

atients used to a high-sodium intake may loseheir appetite and become malnourished if so-ium restriction is instituted too abruptly and tootrictly.63 In these patients, sodium restrictionhould be introduced gradually to provide timeor taste adjustment. By cutting back gradually,ost patients find that they do not miss the salt.8.4: Fluid intake should be restricted in chil-

ren with CKD stages 3 to 5 and 5D who areligoanuric to prevent the complications of fluidverload. (A)Children with oliguria or anuria need to limit

heir fluid intake to avoid associated complica-ions of altered fluid status, including hyperten-ion. Fluid restriction for oligoanuric children onD therapy is also indicated, and an interdialytic

ncrease above their “dry” weight (�5% of theirry weight) is expected and desirable. Severeestriction of food (and fluid) intake by childrenor the purpose of avoiding extra HD sessionsosters malnutrition and should be discouraged.

Daily fluid restriction � insensible fluid lossesTable 27) � urine output � amount to replacedditional losses (eg, vomiting, diarrhea, enteros-

omy output) � amount to be deficited.

awrybagiusiideoateer

sRoitfl

ch

ieimomsnofaw

pGmu(sia

tafclacvsm

pevdtSimBe14rhmcmfmmratafm(mpg

PNC

Fluid and Electrolyte Requirements and Therapy S73

To restrict fluid intake, children should bedvised to reduce their intake of beverages, asell as foods that are liquid or semiliquid at

oom temperature (eg, ice, soup, Jell-O, ice cream,ogurt, pudding, and gravy). This can be achievedy drinking only when thirsty, taking smallmounts throughout the day using small cups orlasses, quenching thirst by sucking on crushedce, eating cold fruit, chewing gum, gargling orsing breath sprays/sheets, and avoiding high-odium or very sweet foods. About 80% of anndividual’s total water intake comes from drink-ng water and beverages and the other 20% iserived from food.448 Many fruits and veg-tables contain lots of water and can inconspicu-usly add to a child’s fluid intake. These foodsre not restricted routinely. The free water con-ent of infant formulas (�90% by volume) andnteral feedings (70% to 85%) should be consid-red when formulating feeding regimens for fluid-estricted children (see Appendix 3, Table 36).

Attempts at fluid restriction may be futile ifodium is not restricted at the same time.63

educing fluid intake alone is not practical mostf the time because the increased ECF osmolal-ty brought about by the excessive sodium inges-ion will stimulate thirst, followed by furtheruid ingestion and isotonic fluid gain.63,463,464

8.5: Potassium intake should be limited forhildren with CKD stages 2 to 5 and 5D whoave or are at risk of hyperkalemia. (A)Ninety-eight percent of the body’s potassium

s contained in cells, whereas only 2% is in thextracellular compartment. Potassium moves rap-dly between the intra- and extracellular compart-

ents to maintain normal serum levels. Becausef the uneven distribution between compart-ents, small shifts can result in major changes in

erum potassium concentrations. Maintaining aormal serum potassium concentration dependsn these shifts, as well as excretion of potassiumrom the body. Intestinal excretion accounts forpproximately 10% of potassium excretion,

Table 27. Insensible Fluid Losses

Age Group Fluid Loss

reterm infants 40 mL/kg/deonates 20-30 mL/kg/dhildren and adolescents 20 mL/kg/d or 400 mL/m2

hereas the remainder is excreted in urine. Renal p

otassium excretion typically is maintained untilFR decreases to less than 10 to 15 mL/min/1.732. The risk of hyperkalemia is also increased by

rinary obstruction, rhabdomyolysis, hemolysiseg, blood transfusions and tumor lysis), acido-is, or treatment with potassium-sparing diuret-cs, angiotensin-converting enzyme inhibitors, orngiotensin receptor blockers.

Extracellular potassium influences muscle ac-ivity, especially the heart. Both hypokalemiand hyperkalemia cause alterations in all muscleunction (skeletal, myocardial, and smooth muscleontractility) and cardiac arrhythmias. Hyperka-emia is common in patients with CKD stage 5nd, when severe, can rapidly lead to death fromardiac arrest or paralysis of muscles that controlentilation. Therefore, control of serum potas-ium is a critically important part of dietaryanagement in patients with CKD.When the kidney loses its ability to filter

otassium (K), counseling children and caretak-rs to limit dietary potassium is critical to pre-ent and manage hyperkalemia. There are noata for the degree of dietary potassium restric-ion required for children with hyperkalemia.uggested dietary management of hyperkalemia

n adults limits intake to less than 2,000 to 3,000g (�50 to 75 mmol/d) of K daily.444,465,466

ased on a 70-kg standard adult, this is thequivalent of less than 30 to 40 mg/kg/d (�0.8 tommol/kg/d). For infants and young children,

0 to 120 mg (1 to 3 mmol/kg/d) of K may be aeasonable place to start. Breast milk (mature)as the lowest potassium content (546 mg/L; 14mol/L) compared with standard commercial

ow’s milk-based infant formulas (700 to 740g/L; 18 to 19 mmol/L). Volumes of infant

ormula of 165 mL/kg or greater will exceed 120g (3 mmol) K/kg and may aggravate hyperkale-ia. Children can lower potassium intake by

estricting intake of such high-potassium foodss bananas, oranges, potatoes and potato chips,omato products, legumes and lentils, yogurt,nd chocolate.460 The nutrition facts panel onood labels is not required to list potassium, butay provide potassium content as actual amount

mg) and % DV. Foods containing less than 100g or less than 3% DV are considered low in

otassium. Foods containing 200 to 250 mg orreater than 6% DV are considered high in

otassium (http://www.kidney.org/ATOZ/atoz

Ia1nst5

tascqtst

echpsidilb

tebfflrtl1itrcis

�rmcpo

i

●

●

●

i

●

doftmTtipf

vr

●

●

Recommendation 8S74

tem.cfm?id�103; http://www.kidney.org/Atoz/tozItem.cfm?id�148; last accessed November2, 2008).467 If potassium is not listed, it doesot mean that the food does not contain potas-ium. Presoaking root vegetables, including pota-oes, effectively lowers potassium content by0% to 75%.468,469

Salt substitutes, also referred to as light salts,ypically replace all or some of the sodium withnother mineral, such as potassium or magne-ium. Salt substitutes that contain potassium mayause hyperkalemia with life-threatening conse-uences in individuals with hyperkalemia or aendency toward it.470 Potassium-containing saltubstitutes are inappropriate for people who needo limit both salt and potassium.

When hyperkalemia persists, despite strict adher-nce to dietary potassium restriction, nondietaryauses of hyperkalemia—such as spurious values,emolysis, metabolic acidosis, other exogenousotassium sources, constipation, inadequate dialy-is, medications (angiotensin-converting enzymenhibitors, angiotensin-receptor blockers, nonsteroi-al anti-inflammatory agents, and potassium-spar-ng diuretics), and tissue destruction due to catabo-ism, infection, surgery, or chemotherapy—shoulde investigated further.471,472

Moderate to severe hyperkalemia may requirereatment with a potassium binder. When oral,nteral, or rectal administration of potassium-inding resins is ineffective, undesirable, or noteasible, infant formula, enteral feedings, or otheruids can be pretreated to safely and effectivelyeduce their potassium content. Depending onhe dosage of potassium binder used, this processowers the potassium content of the feeding by2% to 78%.473-477 This process also may bendicated when there are concerns about obstruc-ion of an enteral feeding tube. In addition toeducing potassium content, other reportedhanges associated with binder use include anncrease or reduction in other nutrients, such asodium and calcium.

Children on PD or frequent HD therapy (ie,5 sessions/wk) rarely need dietary potassium

estriction and may actually develop hypokale-ia. Normokalemia may be achieved through

ounseling and frequent reinforcement of a high-otassium diet,478 KCl supplements, or addition

f potassium to the dialysate.

COMPARISON TO OTHER GUIDELINES

This guideline is in agreement with the follow-ng CARI CKD Guidelines479:

Supplements of 4 to 7 mmol/kg/d of sodiumchloride may be required to maximize growthin children with CKD and renal dysplasia.Sodium chloride supplements should be givento the limit of tolerance as indicated byincreased blood pressure.When an infant requires high-sodium intake, ahigher sodium renal milk formula (20 mmol/L), where available, may be preferable to astandard infant formula (7 mmol/L) or breastmilk (6 mmol/L).

This guideline did not agree with the follow-ng suggestion in the CARI CKD Guidelines:

Sodium chloride supplements may be addedto a standard infant formula (1/4 metric tea-spoon of table salt � 17 mmol).

No clinical guidelines were found for theegree of potassium restriction for children withr at risk of hyperkalemia. The CARI Guidelinesor adults recommend a reduced potassium diethat limits intake to approximately 50 to 65mol (2,000 to 2,500 mg) of potassium daily.480

he European Best Practice Guidelines on Nutri-ion for adults recommend a daily potassiumntake of 50 to 70 mmol (1,950 to 2,730 mg)otassium daily or 1 mmol/kg ideal body weightor hyperkalemic predialysis patients.309

LIMITATIONS

There are no studies examining the effects ofarious levels of fluid, sodium, or potassiumestriction on outcomes in children with CKD.

RESEARCH RECOMMENDATIONS

Studies to determine the optimal level ofsodium and potassium restriction to controlblood pressure and hyperkalemia in childrenof different ages or body sizes are needed.Studies to identify the best counseling andmotivational methods to improve dietary ad-herence to dietary restriction of fluid, sodium,

and potassium are required.

honitpvp

cfs

dfpn(bkpmjmw(t(

d

NCAAAA

A

RECOMMENDATION 9: CARNITINE

laaHplba

mwtaticctattlGotcoasopcwt

tttdocoiKGwtuc

INTRODUCTION

Patients with CKD stage 5D and receiving HDave repeatedly been shown to have low levelsf endogenous L-carnitine and elevated acylcar-itine levels. Whereas clinical symptoms compat-ble with carnitine deficiency can be evident inhis patient population, there are limited data thatrovide evidence for successful therapeutic inter-ention with L-carnitine supplementation in HDatients.9.1 In the opinion of the Work Group, there is

urrently insufficient evidence to suggest a roleor carnitine therapy in children with CKDtage 5D.

RATIONALE

L-Carnitine is a biologically active amino aciderivative that has a key role in the regulation ofatty acid metabolism and adenosine triphos-hate formation in multiple organs.481 Total car-itine concentration includes both free and boundie, acylated) carnitine, which reflects levels inoth serum and tissues, such as muscle, liver, andidney. Total acylcarnitine levels are increased inatients with CKD stage 5D, with values asuch as 4.6 times greater than in healthy sub-

ects.481 Carnitine deficiency is confirmed byeasurements of plasma free and total carnitineith an acyl:free carnitine ratio greater than 0.4

ie, [total � free carnitine] free carnitine) or aotal serum carnitine value less than 40 �mol/LTable 28).482

Patients who receive HD may be at risk of theevelopment of carnitine deficiency as a result of

Table 28. Normal Serum Carnitine Levels (�mol/L)

Serum FreeCarnitine

Serum TotalCarnitine

eonates* 26-76 35-102hildren 41.4 � 10.0† 56.2 � 11.4†dolescent females† 39.3 � 8.1 53.2 � 8.9dolescent males† 39.6 � 9.3 53.5 � 10.5dult female* 19.3-53.9 28.1-66.4dult male* 34.8-69.5 44.2-79.3

Adapted with permission.482

*Data are presented as 95% CI.

t†Data are presented as mean � SD.

merican Journal of Kidney Diseases, Vol 53, No 3, Suppl 2 (Marc

oss of carnitine during the dialysis procedure, inddition to possible reductions in dietary intakend endogenous synthesis. In turn, patients onD therapy have been documented to have lowlasma and tissue L-carnitine levels.481-484 Faress information pertaining to the relationshipetween dialysis and carnitine deficiency is avail-ble from the PD population.485,486

Carnitine deficiency can result in the develop-ent of anemia, cardiomyopathy, and muscleeakness, all symptoms that may be present in

he dialysis population.481,482,487,488 It is alsossociated with intradialytic hypotension in pa-ients receiving HD. However, studies address-ng the therapeutic use of supplemental L-arnitine in dialysis patients are few and haveharacteristically included small numbers of pa-ients.485,486,489,490 This has compromised anybility to generate definitive evidence supportinghe role of regular supplemental L-carnitine inhe treatment of these symptoms. Along theseines, the KDOQI Adult and Pediatric Workroup on Anemia Management conducted a thor-ugh evaluation of the data particular to thereatment of anemia in patients with CKD andoncluded there was insufficient evidence to rec-mmend a role for carnitine in the treatment ofnemia.491 Most, but not all, of the few pediatrictudies that have been conducted on the subjectf carnitine deficiency in dialysis patients haverovided evidence for an increase in plasmaarnitine level after carnitine supplementationith no associated change in any symp-

oms.485,486,489,490

Although the Work Group cannot recommendhe use of carnitine at this time, it does not wanto discourage any therapeutic trial of carnitine ifhe clinical symptoms are suggestive of the disor-er, especially when the evaluation provides lab-ratory evidence compatible with a diagnosis ofarnitine deficiency. In a manner similar to thatf an NKF Carnitine Consensus Conference andn line with the recommendation from the prior/DOQI Pediatric Nutrition Guidelines, the Workroup believes that a trial may be indicatedhen all other causes for the symptoms in ques-

ion have been excluded and the patient has beennresponsive to standard therapies.487 Althougharnitine supplementation has been provided

hrough the intravenous and oral routes in pa-

h), 2009: pp S75-S76 S75

ttscL

sL

ttmdai

●

●

●

●

Recommendation 9S76

ients with CKD, there have not been compara-ive studies of the 2 routes of therapy despiteignificant differences in their respective pharma-okinetics.485,486,490 The bioavailability of oral-carnitine in patients with CKD is unknown. Intudies of healthy adults, the portion of oral-carnitine that is not absorbed is converted torimethylamine-N-oxide and trimethylamine, me-abolites normally excreted by the kidney. Accu-ulation of these metabolites and their break-

own products in patients with CKD may bessociated with the development of neurotoxic-ty and “uremic breath.”481,487,492

COMPARISON TO OTHER GUIDELINES

The European Pediatric Peritoneal DialysisWorking Group stated that there is no preciseplace for carnitine supplementation in the

treatment of anemia in pediatric PD patients.493

RESEARCH RECOMMENDATIONS

Prospective studies should be conducted toevaluate the impact of carnitine therapy on thecardiac structure/function of patients withCKD stage 5D.Additional studies should evaluate the influ-ence of long-term (� 6 months) treatment ofanemia hyporesponsive to erythropoiesis-stimulating agents with L-carnitine supplemen-tation.Further definition of the L-carnitine responseshould be studied by taking an outcomesapproach to patients treated with L-carnitine.Can patient groups be identified who arelikely to respond to L-carnitine for 1 or moreof its proposed indications? Are certain indi-viduals uniform responders across indicationsor do certain patient characteristics predict

specific responses?

CkaaCtrrhnipnssspctamap

1

1

1

A

RECOMMENDATION 10: NUTRITIONAL MANAGEMENT OF

TRANSPLANT PATIENTS

1

1

1

1

aCmn

sicpi

INTRODUCTION

Transplantation is not a cure. It is a state ofKD regardless of GFR or other markers ofidney damage.494 Management of children withkidney transplant includes care of the graft, butlso care of the complications of CKD.495,496

hildren continue to require dietary modifica-ions after transplantation to address nutrition-elated issues. Early in the transplantation pe-iod, dietary management of hypertension,yperkalemia, hypophosphatemia, hypomag-esemia, and hyperglycemia are required to aidn the management of side effects of immunosup-ressive drugs. Long-term interventions areeeded to prevent or aid management of exces-ive weight gain/obesity, dyslipidemia, andteroid-induced osteoporosis. Children with CKDtages 2 to 5T require dietary management ofrotein and phosphorus in the same way ashildren with similar GFRs before transplanta-ion. Continued assessment of nutrient intake,ctivity level, growth, laboratory values, andedications is suggested to ensure the best short-

nd long-term outcomes for children after trans-lantation.

0.1 Dietary assessment, diet modifications,and counseling are suggested for chil-dren with CKD stages 1 to 5T to meetnutritional requirements while minimiz-ing the side effects of immunosuppres-sive medications. (C)

0.2 To manage posttransplantation weightgain, it is suggested that energy require-ments of children with CKD stages 1 to5T be considered equal to 100% of theEER for chronological age, adjusted forPAL and body size (ie, BMI). (C) Furtheradjustment to energy intake is suggestedbased upon the response in rate of weightgain or loss. (C)

0.3 A balance of calories from carbohydrate,protein, and unsaturated fats within thephysiological ranges recommended bythe AMDR of the DRI is suggested for

children with CKD stages 1 to 5T to t

merican Journal of Kidney Diseases, Vol 53, No 3, Suppl 2 (Marc

prevent or manage obesity, dyslipide-mia, and corticosteroid-induced diabe-tes. (C)

0.4 For children with CKD stages 1 to 5Tand hypertension or abnormal serummineral or electrolyte concentrations as-sociated with immunosuppressive drugtherapy or impaired kidney function,dietary modification is suggested. (C)

0.5 Calcium and vitamin D intakes of atleast 100% of the DRI are suggested forchildren with CKD stages 1 to 5T. (C) Inchildren with CKD stages 1 to 5T, it issuggested that the total oral and/or en-teral calcium intake from nutritionalsources and phosphate binders not ex-ceed 200% of the DRI (see Recommenda-tion 7.1). (C)

0.6 Water and drinks low in simple sugarsare the suggested beverages for chil-dren with CKD stages 1 to 5T with highminimum total daily fluid intakes (ex-cept those who are underweight, ie,BMI-for-height-age < 5th percentile)to avoid excessive weight gain, pro-mote dental health, and avoid exacer-bating hyperglycemia. (C)

0.7 Attention to food hygiene/safety andavoidance of foods that carry a high riskof food poisoning or food-borne infectionare suggested for immunosuppressedchildren with CKD stages 1 to 5T. (C)

RATIONALE

10.1: Dietary assessment, diet modifications,nd counseling are suggested for children withKD stages 1 to 5T to meet nutritional require-ents while minimizing the side effects of immu-osuppressive medications. (C)The short- and long-term effects of immuno-

uppressive medications present new and famil-ar nutritional challenges to children and theiraregivers that change during the course of theosttransplantation period. Goals of nutritionn the immediate and short-term posttransplan-

ation period are to encourage intake, promote

h), 2009: pp S77-S83 S77

apestospgssf

cctdtpdpdknacndhr

ct

misrHtd

baiamowt

gcea(sw

trh

AC

C

SM

DOR

Recommendation 10S78

nabolism and wound healing, maintain bloodressure control, and maintain glucose, min-ral, and electrolyte balance. In the long-termtage of transplantation, nutritional goals areargeted to preventing chronic complicationsf immunosuppressive therapy, such as exces-ive weight gain/obesity, hyperlipidemia, hy-ertension, and corticosteroid-induced hyper-lycemia and/or osteoporosis. Diet counselinghould begin early to review the dietary pre-cription, nutrition-related medication side ef-ects, and the nutrition care plan.

The first 3 to 6 months after transplantationan be very challenging for children and theiraretakers, with many new routines and medica-ions to learn. Because diets are advanced imme-iately after transplantation, it is recommendedhat patients be evaluated for appropriate energy,rotein, carbohydrate, and fat intakes. If there iselayed normalization of kidney function, it isrudent to follow restrictions similar to thoseescribed for those with CKD stages 2 to 5 untilidney function normalizes. Over time, as immu-osuppressant dosages decrease and their associ-ted side effects recede, dietary modificationsan be liberalized. Although many patients resisteeding to follow a special posttransplantationiet, this is an appropriate time to instruct aealthy diet for age with a strong emphasis onegular exercise.

Table 29 lists nutrition-related side effects of

Table 29. Nutrition-Related Side-Ef

Maintenance Agents

zathioprineorticosteroids (prednisone, methylprednisolone)

alcineurin inhibitors (cyclosporine, tacrolimus)

irolimusycophenolate or Mycophenolic acid

Induction Agents

aclizumabKT-3abbit antithymocyte globulin (ATG, thymoglobulin)

Adapted with permission.497

urrently used immunosuppressive agents inransplant patients.

Several of the side effects listed are transient anday last for only several weeks or months. Just as

n the pretransplantation period, adaptation to someide effects often is possible, enabling a child toeturn to normal activities of living despite them.owever, others present potentially life-long issues

hat will need to be considered for at least theuration of the transplant.

The frequency of nutritional assessment maye highest in the early posttransplantation periodnd decreases as the dosage and side effects ofmmunosuppressive medications are reduced. Atminimum, the frequency of nutritional assess-ent should be compatible with age- and stage-

f-CKD–matched recommendations for childrenith CKD stages 2 to 5 and 5D (Recommenda-

ion 1, Table 1).10.2: To manage posttransplantation weight

ain, it is suggested that energy requirements ofhildren with CKD stages 1 to 5T be consideredqual to 100% of the EER for chronologicalge, adjusted for PAL and body size (ie, BMI).C) Further adjustment to energy intake isuggested based upon the response in rate ofeight gain or loss. (C)There is no evidence that children who are

ransplanted have increased or decreased energyequirements compared with healthy children;owever, excessive weight gain in children who

f Immunosuppressive Medications

Nutrition Side-Effects

usea, vomiting, sore throat, altered taste acuityperglycemia, hyperlipidemia, sodium retention,hypertension, increased appetite and weight gain,osteoporosis, calciuria, muscle wasting, peptic ulcerdisease, impaired wound healing, electrolytedisturbancesperlipidemia, hyperglycemia, hypomagnesemia,hyperkalemia, hypertensionoid grapefruitperlipidemia, gastrointestinal symptomsrrhea, nausea

Nutrition Side-Effects

nimal side-effectsusea, vomiting, diarrhea, loss of appetitecreased appetite

fects o

NaHy

Hy

AvHyDia

MiNaDe

upwifwaaaanogto

ottcThS(3hoctatitqa

tdvvctcwtytrhh

oo

rsb1shha1GCptt

aoawpmoh

arbrmmchpacwsi

dpAwod

t

Nutritional Management of Transplant Patients S79

nderwent transplantation can occur due to im-roved appetite associated with feeling well, asell as appetite stimulation from corticosteroid

mmunosuppressive medications. Recent datarom the NAPRTCS show a rapid increase ineight for all age groups in the first 6 months

fter transplantation, with children increasing anverage of 0.89 SD in weight in the first yearfter transplantation, with relative stability inverage standardized weight scores during theext 5 years.21 Whether a child is under- orverweight going into transplantation, calorieoals should be established after transplantationo achieve appropriate weight gain, maintenance,r loss.Although most children with CKD are not

verweight, recent data for growth and transplan-ation show that height and weight at the time ofransplantation have increased and that morehildren are obese going into transplantation.he difference between mean pretransplantationeight and weight SDS in 1987 was around 1DS, but had increased to 1.5 SDS in 2006web.emmes.com/study/ped; last accessed March0, 2008), suggesting that children are noweavier for their height (overweight) at the timef transplantation. This is reflected in the in-reased prevalence of obesity in the pretransplan-ation setting from 8% before 1995 to 12.4%fter 1995.21 Obesity may develop after transplan-ation, and weight gain may be more significantn those who were obese before transplanta-ion.176 Mitsnefes et al176 found that the fre-uency of obesity doubled during the first yearfter transplantation.

Obese children going on to kidney transplanta-ion have shown increased risk of mortality andecreased long-term kidney allograft sur-ival.176,498 Additionally, in a retrospective re-iew of pediatric kidney allograft recipients,hildren who were obese (BMI � 95th percen-ile) at the time of transplantation had signifi-antly worse 1-year allograft function comparedith children who were not obese at the time of

ransplantation, but who became obese after 1ear and children who were not obese beforeransplantation or 1 year later.176 The differenceemained significant after adjusting GFR toeight. A greater incidence of posttransplantation

ypertension in obese children may explain the m

bserved association between pretransplantationbesity and decreased GFR.In the general population, obese children are at

isk of high total cholesterol levels (15.7% ver-us 7.2%), high LDL (11.4% versus 7.7%) ororderline LDL cholesterol levels (20.2% versus2.5%), low HDL cholesterol levels (15.5% ver-us 3%), high TG levels (6.7% versus 2.1%),igh fasting glucose levels (2.9% versus 0%),igh glycohemoglobin levels (3.7% versus 0.5%),nd high systolic blood pressure (9.0% versus.6%) compared with healthy-weight children.242

iven that the major cause of mortality in theKD stage 5 population is cardiac related, theediatric population, who are relatively young inhe CKD process, stand to benefit from interven-ions to reduce obesity early in life.

For these reasons, it is important that patientsnd families be counseled on the potential risksf excessive weight gain and educated aboutppropriate dietary and exercise modification foreight control both before and after kidney trans-lantation.21 Interventional strategies for treat-ent of child and adolescent overweight and

besity in the non-CKD population45 may beelpful.Data from studies in the general population

nd the lack of adverse effects make compellingeasons for recommending that exercise, in com-ination with diet, be encouraged in transplantecipients to prevent and/or aid in the manage-ent of overweight, hypertension, and dyslipide-ia. Recommendations for children include en-

ouraging time spent in active play (goal � 1/d) and limiting screen time (television � com-uter � video games) to 2 h/d or less.173 Fordolescents and adults, recommendations in-lude moderate physical activity 3 to 4 timeseekly (20- to 30-minute periods of walking,

wimming, and supervised activity within abil-ty), as well as resistance exercise training.499

10.3: A balance of calories from carbohy-rate, protein, and unsaturated fats within thehysiological ranges recommended by theMDR of the DRI is suggested for childrenith CKD stages 1 to 5T to prevent or managebesity, dyslipidemia, and corticosteroid-in-uced diabetes. (C)Dyslipidemia occurs frequently after kidney

ransplantation and promotes atherosclerosis; it

ay be associated with proteinuria in chronic

aaplp7polpfvpctactiecc(a3ossmhthf(fmlcitfetwlbttsiM

ttmsoa

esiccspdWnwpimttt

ilrfpcsc

aoikg

ptaptd6cDb

Recommendation 10S80

llograft nephropathy, recurrent disease, obesity,nd/or immunosuppressive medications. The re-orted prevalence of increased LDL cholesterolevels (�100 mg/dL) in pediatric kidney trans-lant recipients studied in the 1990s ranged from2% to 84%.223,500-503 The risk and rates ofosttransplantation dyslipidemia may differ basedn the type of immunosuppression used, withower prevalences reported with more recentrotocols, including those that are steroidree.504-506 It is estimated that there are 20 cardio-ascular events/1,000 patients per year after trans-lantation.507 Immunosuppressive agents, espe-ially calcineurin inhibitors, directly contributeo side effects of hypertension, hyperlipidemia,nd nephrotoxicity.508,509 It is generally ac-epted that dietary protein and carbohydrate in-ake do not influence CVD risk as much as fatntake. A study performed primarily to follow theffect of diet on plasma fatty acid levels in 29hildren and adolescents concluded that dietsontaining protein intakes appropriate for ageRDA), a generous carbohydrate intake featuring

low glycemic load, and fat intakes less than0% of total caloric intake were reasonable goalsf diet therapy after transplantation.510 Anothertudy of 45 patients did not find diet to conclu-ively explain the higher prevalence of dyslipide-ia in their transplant patients compared with

ealthy controls.284 However, they recommendedhat all patients with CKD be counseled in a dietigh in polyunsaturated fats and low in saturatedats. Children adhering to the Step II AHA diet�30% total calories from fat, �7% caloriesrom saturated fat, 10% polyunsaturated fat, �200g/d cholesterol)511 had an 11% reduction in TG

evels and a 14% reduction in LDL cholesteroloncentration. In a study of the role of dietaryntervention on metabolic abnormalities and nu-ritional status after transplantation, adults whoollowed a prescribed diet (AHA Step I Diet) andxercise regimen for the first year after transplan-ation showed significant improvements ineight, body fat, fasting glucose, and cholesterol

evels; nonadherent patients experienced small,ut insignificant, increases in the first 3 parame-ers and a significant increase in serum choles-erol levels.512 Therefore, a first-line treatmenthould include a trial of diet modification limit-ng saturated fat, cholesterol, and simple sugars.

ore current dietary recommendations aimed at t

he early prevention of CVD are available fromhe AHA.239 In children who resist overt dietary

odification, healthy food preparation methodshould at least be emphasized, including the usef such heart-friendly fats as canola or olive oilsnd margarines.

Glucose intolerance and hyperglycemia occurarly after transplantation in association withurgical stress and corticosteroid and calcineurinnhibitor therapy, with serum glucose levels de-reasing as immunosuppressant dosages de-rease. Patients should be counseled to avoidimple sugars in the early posttransplantationeriod (the first 3 to 6 months) when steroidoses are highest and weight gain is most rapid.hen blood sugar levels stabilize, it may still be

ecessary to restrict simple sugars to manageeight gain and hypertriglyceridemia. Posttrans-lantation diabetes mellitus occurs occasionallyn pediatric kidney patients (2.6%) and is seenost frequently within the first year of transplan-

ation.513 Children with a family history of diabe-es are at higher risk of posttransplantation diabe-es.

Previous recommendations for increased DPIn the early posttransplantation period are noonger warranted. Given the quick postoperativeecovery of most children and the current steroid-ree or rapid-steroid-taper protocols used, com-ensation for increased nitrogen losses, proteinatabolism, and decreased protein anabolism as-ociated with surgical stress and high-dose corti-osteroid therapy is no longer justified.

10.4: For children with CKD stages 1 to 5Tnd hypertension or abnormal serum mineralr electrolyte concentrations associated withmmunosuppressive drug therapy or impairedidney function, dietary modification is sug-ested. (C)The majority of children who underwent trans-

lantation are hypertensive and receive antihyper-ensive medications throughout the immediatend follow-up posttransplantation period. Ap-roximately 80% of children are hypertensive inhe early posttransplantation period. This rateecreases to 65% to 73% at 2 years and 59% to9% at 5 years after transplantation (web.emmes.om/study/ped; last accessed March 30, 2008).ietary sodium restriction is indicated to aid inlood pressure management (see Recommenda-

ion 8).

twetssm

tttLichppsms

ctscsr

ldwtne7

tsl

Ccrifibbsitla(reotdctabC

tCt

m8gcbctR

aw

CPPT

Nutritional Management of Transplant Patients S81

Hyperkalemia in the immediate posttransplan-ation period occurs frequently in associationith the medications cyclosporin and tacrolimus,

specially when blood levels achieve or exceedherapeutic targets. Serum potassium levelshould be monitored and a low-potassium diethould be implemented as indicated (see Recom-endation 8).Hypophosphatemia is a common complica-

ion seen in the early stage of kidney transplan-ation, occurring in up to 93% of adults duringhe first few months posttransplantation.514

ow serum levels occur in association with anncrease in urinary phosphate excretion, de-reased intestinal phosphate absorption, andyperparathyroidism that persists beyond theretransplantation period.514 Children with hy-ophosphatemia can be encouraged to con-ume a diet high in phosphorus (see Recom-endation 5, Table 13); however, phosphorus

upplements usually are required.121

Hypomagnesemia, a common side effect ofalcineurin inhibitors, occurs early in the post-ransplantation period. Increased dietary magne-ium intake may be attempted; however, as in thease of hypophosphatemia, the amount of magne-ium required to correct serum levels typicallyequires a magnesium supplement.

10.5: Calcium and vitamin D intakes of ateast 100% of the DRI are suggested for chil-ren with CKD stages 1 to 5T. (C) In childrenith CKD stages 1 to 5T, it is suggested that the

otal oral and/or enteral calcium intake fromutritional sources and phosphate binders notxceed 200% of the DRI (see Recommendation.1). (C)After transplantation, children are predisposed

o progressive bone disease and osteoporosis foreveral reasons. They are likely to have preestab-

Table 30. Recommended Frequency of MeasuAfter

Parameter Week 1 First 2 Months

alcium Daily Weeklyhosphorus Daily WeeklyTH Optional At 1 month, then optionalotal CO2 Daily Weekly

Adapted with permission.121

ished metabolic bone disease associated with t

KD. After transplantation, corticosteroids, cal-ineurin inhibitors, and residual hyperparathy-oidism may increase the risk of bone demineral-zation,121 with bone loss most rapid during therst year after transplantation.515 Osteopenia haseen confirmed by using bone biopsy data and/orone densitometry.516 Interpretation of DXA mea-urement of bone mineral density is complicatedn children with delayed growth and matura-ion,121,517 and estimates of the perceived preva-ence of moderate plus severe osteopenia varyccording to analysis based on chronological age42%), height-age (15%), or sex-matched (23%)eference data.516 Whether deficits in bone min-ral density are reversible upon discontinuationf glucocorticoids is unclear. Pediatric kidneyransplant recipients also are at increased risk ofeveloping disabling bone disease, such as avas-ular necrosis and bone fractures. In addition,ransplantation is part of the continuum of CKD,nd progressive damage to the graft will result inone mineral disorders similar to the effects ofKD in the native kidney.121

Because of these issues, it is recommendedhat serum levels of calcium, phosphorus, totalO2, and PTH continue to be monitored after

ransplantation (Table 30).121

To minimize bone mineral loss, daily supple-entation at the level of the DRI for calcium and

00 to 1,000 IU of vitamin D has been sug-ested; however, there are no data for efficacy inhildren. Children with CKD stages 3 to 5T withone mineral disorders should be managed ac-ording to established recommendations for non-ransplantation children with similar GFRs (seeecommendation 7).10.6: Water and drinks low in simple sug-

rs are the suggested beverages for childrenith CKD stages 1 to 5T with high minimum

t of Calcium, Phosphorus, PTH and Total CO2

lant

2-6 Months �6 Months

ly

As per guidelines for stage of CKDlyal initially, optional

ly

remenTransp

MonthMonthIf normMonth

otal daily fluid intakes (except those who are

uppi

fusosculcfllflwtika

apgC

ttaiLgt

wtObiaptuacfitiiph(bnla

o

taa

●

●

●

●

●

●

●

●

Recommendation 10S82

nderweight, ie, BMI-for-height-age < 5thercentile) to avoid excessive weight gain,romote dental health, and avoid exacerbat-ng hyperglycemia. (C)

Good graft function after transplantation af-ects fluid and electrolyte balance. A high vol-me of fluid intake generally is prescribed totimulate kidney function, replace high urineutput, and regulate intravascular volume. Con-umption of large volumes of fluids with highalorie, fat, or simple sugar content can contrib-te to obesity and exacerbate increased serumevels of glucose and TG. With the exception ofhildren needing to gain weight, the majority ofuid intake should come from water, fat-free or

ow-fat milk, and sugar-free drinks. Increasinguid intake frequently is challenging for childrenho followed a strict fluid restriction or were

ube fed before transplantation. In some children,ncluding infants and toddlers receiving an adultidney, enteral hydration continues to be neededfter transplantation.

10.7: Attention to food hygiene/safety andvoidance of foods that carry a high risk of foodoisoning or food-borne infection are sug-ested for immunosuppressed children withKD stages 1 to 5T. (C)Immunosuppressed patients are more prone

o develop infections, potentially includinghose brought on by disease-causing bacteriand other pathogens that cause food-bornellness (eg, Escherichia coli, Salmonella, andisteria monocytogenes). Many patients areiven gastric acidity inhibitors after transplan-

Table 31. General Food Safety Recomm

Clean: To avoid spreading bacteria throughout the kitcheSeparate: Avoid spreading bacteria from one food to anoseafood, and eggs away from ready-to-eat foods.Cook to proper temperatures: Foods are safely cooked winternal temperature.Chill: Refrigerate foods promptly to slow the growth of haRead labels to avoid purchasing food that is past its “sellBuy only pasteurized milk, cheese, and other dairy produjuice selected from the refrigerated section of the store isPurchase canned goods that are free of dents, cracks, orWhen eating out, avoid foods containing uncooked ingredmay contain undercooked foods or foods that have been

Source: US Department of Agriculture (USDA).519

ation; these medications have been associated d

ith increased risk of intestinal and respira-ory infections in nontransplanted children.518

f concern are the common symptoms of food-orne illness that include diarrhea and vomit-ng, both of which may lead to dehydrationnd/or interfere with absorption of immunosup-ressive medications. Foods that are most likelyo contain pathogens fall into 2 categories:ncooked fresh fruits and vegetables, and suchnimal products as unpasteurized milk, softheeses, raw eggs, raw meat, raw poultry, rawsh, raw seafood, and their juices. Although

he risk of infection from food sources inmmunosuppressed kidney transplant patientss unknown, it seems prudent that transplantatients be educated about safe practices whenandling, preparing, and consuming foodsTable 31).519 Theoretically, food safety woulde most important during periods when immu-osuppression dosing is at its highest andiberalization or discontinuation could occurs immunosuppressant doses decrease.

COMPARISON TO OTHER GUIDELINES

The KDIGO Transplant Guideline is in devel-pment.

LIMITATIONS

The majority of research in posttransplanta-ion nutrition has been conducted in adults. Therere no controlled studies of the effect of calciumnd vitamin D supplementation on bone mineral

tions for Immunosuppressed Children

h hands and food preparation surfaces often.keeping high-risk foods such as raw meat, poultry,

ey are heated to the USDA-recommended safe minimum

acteria.use by” date.

the refrigerated section. Read labels to be sure that fruitrized.

g lids.uch as eggs, meat, poultry, or fish. Avoid buffets, whichtemperature too long.

enda

n, wasther by

hen th

rmful bby” or “cts frompasteubulginients sat room

ensity after transplantation.

●

●

●

Nutritional Management of Transplant Patients S83

RESEARCH RECOMMENDATIONS

Determine energy and protein requirements ofchildren on corticosteroid therapy after trans-plantation;Determine whether dietary intervention iseffective in minimizing posttransplantationweight gain, and if so, methods to motivate

children to embrace a heart-healthy diet andregular exercise after transplantation;Determine whether posttransplantation cal-cium and vitamin D supplementation in chil-dren on corticosteroid therapy positively im-pact on bone mineral density and decrease therisk of osteopenia, osteoporosis, avascularnecrosis, and fractures.

uhb

mu

E

alpnm

P

ioccnetsafBiutmn

s

E

(mt

S

APPENDIX 1: PROCEDURES FOR MEASURING GROWTH PARAMETERS

P

swaatmaalatotm(ct

E

a

P

cCitu(

E

P

izsoaaf

GROWTHPARAMETERSTOBEMEASURED

Standard measurement techniques should besed for all growth parameters.298 Ideally, length/eight and head circumference measures shoulde performed by the same person each time.

RECUMBENTLENGTH

Measured in children up to approximately 24onths of age or in older children who are

nable to stand without assistance.

quipment

Infant stature board with a fixed headboardnd a moveable footboard positioned perpendicu-ar to the table surface and a rule along 1 side;en and paper for recording. Two persons areecessary: 1 to hold the head and another toeasure.

rocedure

(i) The infant may be measured in light cloth-ng, without foot coverings. (ii) Place the infantn the table, lying on his back. (iii) Hold therown of the infant’s head and bring it gently inontact with the fixed headboard. Align the exter-al auditory meatus and the lower margin of theye orbit perpendicular to the table. (iv) Whilehe head remains in contact with the headboard, aecond measurer grasps 1 or both feet at thenkle. (v) Move the footboard close to the in-ant’s feet as the legs are gently straightened.ring the footboard to rest firmly against the

nfant’s heels, making sure the toes point straightpward and the knees are pressed down on theable. (vi) Read the markings on the side of theeasuring board and record the value to the

earest 0.1 cm.

HEIGHT

Measures the child who is able to stand unas-isted.

quipment

Fixed measuring device attached to a wallstadiometer); block squared at right angles oroveable head projection attached at right angle

o the board; pen and paper for recording. s

American Journal of Kidney D84

rocedure

(i) Have the child remove his or her shoes andtand on the floor, facing away from the wallith heels together, back as straight as possible,

rms straight down; heels, buttocks, shoulders,nd head touching the wall or vertical surface ofhe measuring device. A family member or othereasurer may be necessary to hold the child’s

nkles and knees steadily in place. The child’sxis of vision should be horizontal, with the childooking ahead and the external auditory meatusnd lower margin of the orbit aligned horizon-ally. (ii) Place the head projection at the crownf the head. (iii) Hold the block steady and havehe child step away from the wall. (iv) Note theeasurement and record it to the nearest 0.1 cm.

v) Perform 3 measurements that are within 0.2m of each other and use the average of the 3 forhe final value.

WEIGHT USING AN INFANT SCALE

quipment

Infant scale that allows infant to lie down; pennd paper for recording.

rocedure

(i) Undress the infant completely. (ii) Place alean paper liner in the tray of the scale. (iii)alibrate the scale to zero. (iv) Lay or seat the

nfant in the tray. (v) Read the weight accordingo the type of scale. Make sure the infant isnable to touch the wall or surrounding furniture.vi) Record the weight to the nearest 0.1 kg.

STANDINGWEIGHT

quipment

Scale; pen and paper for recording.

rocedure

(i) The child should be weighed in light cloth-ng without footwear. (ii) Calibrate the scale toero. (iii) Assist the child onto the platform of thecale. (iv) Instruct the child to stand in the centerf the platform with feet flat and heels touching,s erect as possible. (v) If using a beam scale,djust the beam of the scale with the main andractional poise as necessary until the beam

wings freely and comes to rest parallel to the

iseases, Vol 53, No 3, Suppl 2 (March), 2009: pp S84-S85

sttrt

E

p

P

tbrhstctR

oocohpctmonbfa

tGu

wtdSecwcp

gpeLbff

S

2on

alt

Stao

dpt

Procedures for Measuring Growth Parameters S85

cale platform. Activate the digital scale, if this ishe scale used. (vi) Read the measurement fromhe scale, looking squarely at the incrementsather than from an angle. (vii) Record the weighto the nearest 0.1 kg.

HEAD CIRCUMFERENCE

Measured in children up to 36 months of age.

quipment

Firm nonstretchable measuring tape; pen andaper for recording.

rocedure

(i) Have the person assisting hold the infant sohat the head is upright. (ii) Locate the occipitalone at the back of the head, also the supraorbitalidges. (iii) Apply the tape firmly around theead just above the supraorbital ridges at theame level on both sides to the occiput. Move theape up or down slightly to obtain the maximumircumference. The tape should have sufficientension to press the hair against the skull. (iv)ecord the measurement to the nearest 0.1 cm.

EVALUATION OF MEASUREMENTS

Anthropomorphic measures should be plottedn the appropriate growth chart: standing heightr recumbent length, weight, BMI, and headircumference. Low height for chronological ager a low head circumference in proportion toeight may reflect long-term nutritional deficits,articularly in infants. Parental heights should beonsidered when interpreting growth charts. One-ime measurements reflect size, whereas serialeasurements are necessary for the assessment

f growth. Low BMI-for height-age may reflect autritional deficit. In some situations, BMI maye better assessed relative to chronological age;or example, in a fully mature (Tanner stage 5)dolescent.

Individual measurements are evaluated by de-ermining SDS (or z scores) or percentiles.rowth SDS represent the difference, in SD

nits, of an individual child’s value (eg, height or i

eight) and the mean value of a sample popula-ion (eg, mean height or weight of healthy chil-ren of the same age and sex). Percentiles andDS are interchangeable; they are 2 ways ofxpressing the same information. For example, ahild on the 50th percentile of height for ageould have an SDS of 0. About 95% of healthy

hildren will have an SDS between �2.0 (�3rdercentile) and �2.0 (�97th percentile).Measures may be plotted on the standardized

rowth charts enclosed in these guidelines (Ap-endix 5).33,34,52 These growth charts were gen-rated by using a statistical method calledMS.520 Calculation of exact SDS can be doney using data from tables of L, M, and S valuesor each measure and entering them into theollowing equation:

DS �

[(observed measure M)L � 1] (L � S)

The US National Center for Health Statistics000 Growth Charts LMS tables are availablen-line at: www.cdc.gov/nchs/about/major/hanes/growthcharts/datafiles.htm.The WHO Growth Standards LMS tables are

vailable in downloadable documents34,52 on-ine at: www.who.int/childgrowth/standards/echnical_report/en/index.html.

EXAMPLE: To calculate the height-for-ageDS for an 8.5-year-old girl, one would look up

he L, M, and S values from the appropriate tablend enter them into the equation, along with herbserved height (eg, 120.6 cm):

SDS � [(120.6 M)L � 1] (L � S)

SDS � [(120.6 130.6)0.0027 � 1] (0.0027 � 0.0463)

SDS � �1.72

Alternatively, several on-line calculators orownloadable software packages are available toerform these calculations. On-line resources,he data sources for each, and the measures

ncluded in each are provided in Appendix 2.

U

W

N

G

S

B

U

B

S

APPENDIX 2: RESOURCES FOR CALCULATING ANTHROPOMETRICSDS/PERCENTILES, ENERGY REQUIREMENTS,

AND MIDPARENTAL HEIGHTTable 32. Resources for Calculating Anthropometric SDS and Percentiles

Source Program Link

Weight-for-Age

z-Score

Height-for-Age

z-Score

HeadCircumference-for-Age z-Score

BMI-for-Agez-Score

HeightVelocityz-Score

.S. Centers forDiseaseControl &Prevention(CDC)

Epi Info NutStat-basedon 2000 CDCgrowth charts

http://www.cdc.gov/epiinfo/ ✓ ✓ ✓ ✓

orld HealthOrganization(WHO)

WHO Anthro—basedon 2006 WHOGrowth Standards(birth-5 years)

http://www.who.int/childgrowth/software/en/

✓ ✓ ✓ ✓

orth AmericanPediatricRenalTransplantCooperativeStudy(NAPRTCS)

Growth ChartCalculator-basedon 2000 CDCgrowth charts

http://spitfire.emmes.com/study/ped/resources/htwtcalc.htm

✓ ✓

enentech GenenCALC-based on2000 CDC growthcharts

Diskette obtained from Genentechrepresentative

✓ ✓ ✓ ✓

tatCoder STAT Growth-BP forhand-helds

http://www.statcoder.com/growthcharts.htm

✓ ✓ ✓ ✓

aylor Collegeof Medicine

Kids BMI Calculator http://www.kidsnutrition.org/bodycomp/bmiz2.html

✓

Table 33. Resources for Calculating Midparental Height

Source Program Link

pToDate Calculator: Midparental Target Height Prediction http://www.uptodate.com/patients/content/topic.do?topicKey�pediendo/2375

Table 34. Resources for Calculating Estimated Energy Requirements

Source Program Link

aylor College of Medicine Kids Energy Calculator http://www.kidsnutrition.org/energy_calculator.htm

American Journal of Kidney Diseases, Vol 53, No 3, Suppl 2 (March), 2009: p S8686

M

F

B

N

F

A

APPENDIX 3: NUTRIENT CONTENT INFORMATIONTable 35. Actual and Adjusted Amounts and Ratios of Phosphorus to Protein in Specific Foods

Food Amount

Actual Contentof Phosphorus

(mg)Actual Contentof Protein (g)

Ratio of mgPhosphorusto g Protein

Phosphorus Content(mg) Adjusted for

Bioavailability

Protein Content (g)Adjusted forDigestibility

Ratio of mg Phosphorusto g Protein Adjusted for

Digestion andAbsorption

eat/Poultry/EggPork loin 3 oz 146 22 6.6 102 20.9 4.9Chicken thigh 3 oz 148 22 6.7 104 20.9 4.9Turkey 3 oz 210 28 7.5 147 26.6 5.5Chicken breast 3 oz 196 27 7.3 137 25.7 5.4Beef sirloin 3 oz 203 25 8.1 142 23.8 6.0Veal loin 3 oz 189 22 8.6 132 20.9 6.3Lamb chop 3 oz 190 22 8.6 133 20.9 6.3Ham 3 oz 239 19 12.6 167 18.1 9.3Egg, large 1 86 6 14.3 60 5.7 10.5

ish/SeafoodShrimp 3 oz 116 18 6.4 81 17.1 4.7Crab, dungeness 3 oz 149 19 7.8 104 18.1 5.7Lobster 3 oz 157 17 9.0 110 16.5 6.6Halibut 3 oz 214 23 9.3 150 21.9 6.9Crab, blue 3 oz 175 17 10.3 123 16.2 7.6Salmon 3 oz 282 21 13.4 197 20.0 9.9Fish sticks 3 oz 153 9 17 107 8.6 11.3eans/Legumes/

Tofu/SeedsSoybeans, roasted 1 cup 624 61 10.2 312 51.9 6.0Tofu, firm 100 g 76 6 12.7 38 5.1 7.5Tofu, soft 100 g 52 4 13.0 26 3.4 7.6Beans, lima 1 cup 209 15 13.9 105 12.8 8.2Soybeans, boiled 1 cup 421 29 14.5 211 24.7 8.5Beans, refried 1 cup 217 14 15.5 109 11.9 9.1Beans, black 1 cup 241 15 16.1 121 12.8 9.5Beans, kidney 1 cup 251 15 16.7 126 12.8 9.8Peas, pigeon 1 cup 200 12 16.7 100 10.2 9.8Beans, navy 1 cup 286 16 17.9 143 13.6 10.5Chickpeas 1 cup 216 12 18.2 108 10.2 10.7Sunflower seeds 1 oz 322 6 53.7 161 5.1 31.6uts/Nut ButterPeanut butter,

chunky2 Tbsp 101 8 12.6 51 6.8 7.4

Peanut butter,smooth

2 Tbsp 118 8 14.8 59 6.8 8.7

Peanuts, roasted 1 oz 147 8 18.4 74 6.8 10.8Pistachios 1 oz 137 6 22.8 69 5.1 13.4Almonds 1 oz 139 6 23.2 70 5.1 13.6Walnuts 1 oz 98 4 24.5 49 3.4 14.4Macadamia 1 oz 56 2 28.0 28 1.7 16.5Sunflower seeds 1 oz 327 5 65.4 164 4.3 38.4

ast FoodsHamburger 1 207 27 7.7 124 24.3 5.1Taco Large 313 31 10.1 188 27.9 6.7Hot dog 1 99 9 11 59 8.1 7.3Cheeseburger 1 310 28 11.0 186 25.4 7.3Sausage patty 1 106 10 10.7 74 9.4 7.9Bean/cheese

burrito2 small 180 15 12.0 108 13.5 8

Sub sandwich, coldcuts

1 287 22 13.2 172 19.6 8.8

Chicken sandwich 1 405 29 13.8 243 26.5 9.2Pepperonl pizza 1 slice 222 16 13.9 133 14.4 9.3Peanut butter

sandwich1 168 12 14 101 10.8 9.3

Cheese sandwich,grilled

1 194 10 19 116 9.0 12.7

Beans with pork,tomato sauce

1 cup 285 13 21.9 171 11.7 14.6

Macaroni & cheese,boxed

1 cup 265 11 24.1 159 9.9 16.1

Breakfastsandwich, fastfood

1 egg/cheese/bacon

459 16 28.2 275 14.7 18.8

(Continued)

merican Journal of Kidney Diseases, Vol 53, No 3, Suppl 2 (March), 2009: pp S87-S90 S87

M

O

I

I

I

O

P

Appendix 3S88

Table 35 (Cont’d). Actual and Adjusted Amounts and Ratios of Phosphorus to Protein in Specific Foods

Food Amount

Actual Contentof Phosphorus

(mg)Actual Contentof Protein (g)

Ratio of mgPhosphorusto g Protein

Phosphorus Content(mg) Adjusted for

Bioavailability

Protein Content (g)Adjusted forDigestibility

Ratio of mg Phosphorusto g Protein Adjusted for

Digestion andAbsorption

ilk/DairyCottage cheese,

nonfat1 cup 151 25 6.0 106 23.8 4.4

Cottage cheese,regular

1 cup 297 28 10.6 208 26.6 7.8

Cottage cheese,2%

1 cup 340 31 11.0 238 29.5 8.1

Milk, soy, unfortified 1 cup 126 8 15.8 88 7.6 9.3Cream cheese 2 Tbsp 30 2 15.0 21 1.9 11.0Cheese,

mozzarella1 oz 100 6 16.6 70 5.7 12.2

Cheese, cheddar 1 oz 145 7 20.7 102 6.7 15.3Cheese, swiss 1 oz 171 8 21.4 120 7.6 15.8Sour cream 1 Tbsp 32 1 26.7 22 1.1 19.7Yogurt, regular 4 oz 107 4 26.8 75 3.8 19.7Yogurt, lowfat 4 oz 162 6 27.0 113 5.7 19.9Light cream 1 cup 192 7 27.4 134 6.7 20.2Ice cream, vanilla 1 cup 138 5 27.6 97 4.8 20.3Milk, whole 1 cup 227 8 28.4 159 7.6 20.9Milk, 2% 1 cup 232 8 29.0 162 7.6 21.4Milk, 1% 1 cup 235 8 29.4 165 7.6 21.7Yogurt, nonfat 4 oz 177 6 29.5 124 5.7 21.7Heavy cream 1 cup 149 5 29.8 104 4.8 22.0Milk, nonfat 1 cup 247 8 30.9 173 7.6 22.8Milk, chocolate 1 cup 255 7 36.4 179 6.7 26.8Hot fudge sundae 1 small 227 6 37.8 159 5.7 27.9ther Sources of

PhosphorusIced tea, bottled 12 oz 95 0 90Candy, milk

chocolate1 oz 62 2 27 59

Cola or pepper-type 12 oz 44 0 42Beer 12 oz 43 1 41

Table 36. Nutrient Content* of Feeds and Supplements Used in Children with CKD

Product Manufacturer

Per 100 mLOsmolality

mOsm/kg/H2O

WaterContent

(%)kcalProtein

(g)CHO(g)

Fat(g)

Na(mmol)

K(mmol)

Ca(mg)

PO4(mg)

nfant FeedingsBreast Milk 69 1.3 7.2 4.1 0.7 1.5 60 15 290Enfamil Lipid Mead Johnson 67 1.4 7.3 3.5 0.8 1.9 76 29 300 89Cow & Gate 1* Cow & Gate 67 1.4 7.5 3.5 0.8 1.6 64 25Similac/Similac

AdvanceAbbott 68 1.4 7.3 3.7 0.7 1.8 72 28 300 90

SMA Gold* SMA 67 1.4 7.3 3.6 0.7 1.7 68 24 291nfant Feedings Favorable for CKD

Good Start Nestle 67 1.4 7.5 3.4 0.8 1.8 72 25 265 90Similac PM

60/40Abbott 68 1.5 6.9 3.8 0.7 1.4 56 19 280 90

nfant Feedings Favorable for HypercalcemiaCalcilo XD Abbott 67 1.5 6.8 3.8 0.7 1.4 �6.7 17 190 91Locasol* Scientific Hospital

Supplies66 1.9 7 3.4 1.2 2 �7.2 46 310

therCows milk (full

fat)66 3.2 4.8 3.9 2.4 3.6 144 95 315

ediatric FeedingsKindercal Mead Johnson 106 3 13.5 4.4 1.6 3.4 101 85 440 85Nutren Junior Novartis/Nestle 100 3 12.7 4.2 2 3.4 136 80 350 85Nutrini* Nutricia 100 4.8 12.3 4.4 2.6 2.8 112 50 260 86Nutrini

Energy*Nutricia 150 4.1 18.5 6.7 3.9 4.2 168 75 410 78

Pediasure Abbott 100 3 13.1 3.8 1.7 3.4 136 85 335 84Resource Just

for KidsNovartis/Nestle 100 3 11 5 2.6 2.9 116 80 390 85

(Continued)

A

R

C

G

F

C

P

A

Nutrient Content Information S89

Table 36 (Cont’d). Nutrient Content* of Feeds and Supplements Used in Children with CKD

Product Manufacturer

Per 100 mLOsmolality

mOsm/kg/H2O

WaterContent

(%)kcalProtein

(g)CHO(g)

Fat(g)

Na(mmol)

K(mmol)

Ca(mg)

PO4(mg)

Resource Justfor Kids 1.5 Novartis/Nestle 150 4.2 16.5 7.5 3 3.3 132 99 390–405† 72

dolescent/Adult FeedingsBoost Novartis/Nestle 101 4.2 17.3 1.7 2.4 4.3 127 127 630 85Boost Plus Novartis/Nestle 152 5.9 19 5.8 3.1 4.1 148 127 670 78Ensure Abbott 106 3.8 17 2.5 3.7 4 128 106 590 85Ensure Plus Abbott 150 5.5 21 4.7 4.4 4.6 127 128 680 77Fortislp* Nutricia 150 6 18.4 5.8 3.9 4.1 78 2.3 420-590† 78Nutren 1.0 Nestle 100 4 12.7 3.8 3.8 3.2 67 67 315-370† 85Nutren 1.5 Nestle 150 6 16.9 6.8 5.1 4.8 100 100 430-510† 78

enal FeedingsScientific Hospital

Kindergen* Supplies 101 1.5 11.8 5.3 2 0.6 22.4 18.6 215 80Magnacal

RenalMead Johnson 200 7.5 20 10.1 3.5 3.2 101 80 570 71

Nepro withCarbSteady

Abbott 180 8.1 16.7 9.6 4.6 2.7 108 70 585 73

NovasourceRenal

Nestle 200 7.4 20 10 3.9 2.1 84 65 700 71

Nutren Renal Nestle 200 7 20.5 10.4 3.2 3.2 128 70 650 70RenalCal Nestle 200 3.4 29 8.2 0 0 0 0 600 70Renilon 7.5* Nutricia 200 7.5 20 10 2.6 0.3 12 6 575 71Suplena with

CarbSteady

Abbott 180 4.5 20.5 9.6 3.4 2.9 116 70 600 74

arbohydrateModules

per 100 g

lucosePolymers

Maxijulpowder*

Maxijul liquid*(per 100 ml)

Scientific HospitalSupplies

Scientific HospitalSupplies

380

200

0

0

95

50

0

0

�0.3

�1

�0.05

�0.1

�1.7

0

�1.7

�5

Polycal Nutricia 384 0 96 0.1 0 0 0 0Polycose Abbott 380 0 94 0 5.7 0.3 12 15

at Modules per 100 mLCalogen Nutricia 450 0 0 50 0 0 0 0Microlipid Nestle 450 0 0 50 0 0 0 0MCT oil Nestle 770 0 0 86 0 0 0 0Canola or corn

oil825 0 0 93 0 0 0 0

ombined CHO/Fat Modules

per 100 g

Scientific HospitalDuocal Supplies 492 0 72.7 22.3 �0.9 �0.13 �5.2 �5

rotein Modules per 100 gVitapro* Vitaflo 360 75 9 6 �13 �18 �400 �320Beneprotein Nestle 357 86 0 0 9.3 12.8 512 215

Scientific HospitalProtifar Supplies 373 88.5 �1.5 1.6 1.3 1.3 52 700

*For most current nutrient content check product label or manufacturer’s product monograph. Values listed here aremerican content, unless otherwise indicated with an asterisk (*) for products available in UK only.†Dependent on flavor.

FAKPPQRGRBMCPBQAOBPWOUBCGGCQCBSPBCAW

Appendix 3S90

Table 37. Nutrient Content of Selected Foods High in Fiber

Product Serving Size Fiber (g) Potassium (mg) Phosphorus (mg)

iber One 1/2 cup 13 230 150ll Bran 1/2 cup 10 310 300ellogg’s Raisin Bran 1 cup 8.2 350 200ost Raisin Bran 1 cup 8 380 250ost Bran Flakes 2/3 cup 6 180 150uaker Crunchy Bran 3/4 cup 5 56 36alston Oatmeal 3/4 cup cooked 4.6 116 110reen peas, frozen, boiled 1/2 cup 4.4 134 72aspberries, raw 1/2 cup 4.2 94 8ulgur, cooked 1/2 cup 4.1 62 36ixed vegetables, frozen 1/2 cup 4.0 15 46ommon Sense Oat Bran 1/2 cup 4.0 120 150ear, canned, water pack 1 cup 4.0 129 17lackberries, raw 1/2 cup 3.8 141 15uaker Old Fashioned Oatmeal 1/2 cup dry 3.7 143 183pple, raw, skin 1 Medium 3.7 159 10at Bran, raw 2 Tbsp 3.6 133 172rown rice, cooked 1 cup 3.5 84 162eaches, canned, water pack 1 cup 3.2 242 24heat bran, raw 2 Tbsp 3.1 86 73range, navel, raw 1 medium 3.1 233 25nifiber® 1 Tbsp 3.0 0 0arley, cooked 1/2 cup 3.0 73 42heerios 1 cup 3.0 90 100eneral Mills Wheaties 1 cup 3.0 110 100eneral Mills Raisin Bran 3/4 cup 3.0 220 150arrots, sliced, boiled 1/2 cup 2.6 177 23uaker Oat Bran cereal 1/2 cup 2.3 100 118orn, boiled 1/2 cup 2.3 204 84roccoli, boiled 1/2 cup 2.3 228 4.6pinach, boiled 1/2 cup 2.2 419 150umpernickel bread 1 slice 2.1 67 57russels sprouts, boiled 1/2 cup 2.0 247 44elery, raw 2 large stalks 2.0 332 30merican rye bread 1 slice 1.9 53 40hole-wheat bread 1 slice 1.9 71 64

Adapted with permission.223

C

B

cf

A

APPENDIX 4: INITIATING AND ADVANCING TUBE FEEDINGS

Table 38. Suggested Rates for Initiating and Advancing Tube Feedings

Age Initial Hourly Infusion Daily Increases Goal*

ontinuous Feedings0-1 y 10-20 mL/h or 1-2 mL/kg/h 5-10 mL/8h or 1mL/kg/h 21-54 mL/h or 6 mL/kg/h1-6 yrs 20-30 mL/h or 2-3 mL/kg/h 10-15 mL/8h or 1 mL/kg/h 71-92 mL/h or 4-5 mL/kg/h6-14 yrs 30-40 mL/h or 1 mL/kg/h 15-20 mL/8h or 0.5 mL/kg/h 108-130 mL/h or 3-4 mL/kg/h�14 yrs 50 mL/h or 0.5-1 mL/kg/h 25 mL/8h or 0.4-0.5 mL/kg/h 125 mL/holus Feedings0-1 y 60-80 mL q 4h or 10-15 mL/kg/feed 20-40 mL q 4h 80-240 mL q 4h or

20-30 mL/kg/feed1-6 yrs 80-120 mL q 4h or 5-10 mL/kg/feed 40-60 mL q 4h 280-375 mL q 4h or

15-20 mL/kg/feed6-14 yrs 120-160 mL q 4h or 3-5 mL/kg/feed 60-80 mL q 4h 430-520 mL q 4h or

10-20 mL/kg/feed�14 yrs 200 mL q 4h or 3 mL/kg/feed 100 mL q 4h 500 mL q 4h or

10 mL/kg/feed

Note: Calculating rates based on age and per kilogram body weight is useful for small-for-age patients.Adapted with permission.521

*Goal is expected maximum that child will tolerate; individual children may tolerate higher rates or volumes. Proceedautiously for jejunal feedings. Goals for individual children should be based on energy requirements and energy density ofeeding and therefore may be lower than expected maximum tolerance.

merican Journal of Kidney Diseases, Vol 53, No 3, Suppl 2 (March), 2009: p S91 S91

S

APPENDIX 5: CLINICAL GROWTH CHARTS

WHO Child Growth Standards

Length-for-age BOYSBirth to 2 years (percentiles)

Months

Age (completed months and years)

Leng

th (c

m)

45

50

55

60

65

70

75

80

85

90

95

45

50

55

60

65

70

75

80

85

90

95

1 2 3 4 5 6 7 8 9 10 11 1 2 3 4 5 6 7 8 9 10 11

15th

3rd

97th

50th

85th

Figure 1. WHO Child Growth Standards: Boys length-for-age, birth to 2 years. Reprinted with permission.34

WHO Child Growth Standards

Length-for-age GIRLSBirth to 2 years (percentiles)

Months

Age (completed months and years)

Leng

th (c

m)

45

50

55

60

65

70

75

80

85

90

95

45

50

55

60

65

70

75

80

85

90

95

1 2 3 4 5 6 7 8 9 10 11 1 2 3 4 5 6 7 8 9 10 11

15th

3rd

97th

50th

85th

Figure 2. WHO Child Growth Standards: Girls length-for-age, birth to 2 years. Reprinted with permission.34

American Journal of Kidney Diseases, Vol 53, No 3, Suppl 2 (March), 2009: pp S92-S10092

Clinical Growth Charts S93

WHO Child Growth Standards

Weight-for-age BOYSBirth to 2 years (percentiles)

Months

Age (completed months and years)

Wei

gh

t (k

g)

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

1 2 3 4 5 6 7 8 9 10 11 1 2 3 4 5 6 7 8 9 10 11

15th

3rd

97th

50th

85th

Figure 3. WHO Child Growth Standards: Boys weight-for-age, birth to 2 years. Reprinted with permission.34

WHO Child Growth Standards

Weight-for-age GIRLSBirth to 2 years (percentiles)

Months

Age (completed months and years)

Wei

gh

t (k

g)

2

3

4

5

6

7

8

9

10

11

12

13

14

15

2

3

4

5

6

7

8

9

10

11

12

13

14

15

1 2 3 4 5 6 7 8 9 10 11 1 2 3 4 5 6 7 8 9 10 11

15th

3rd

97th

50th

85th

Figure 4. WHO Child Growth Standards: Girls weight-for-age, birth to 2 years. Reprinted with permission.34

Appendix 5S94

WHO Child Growth Standards

Birth to 2 years (percentiles)

Length (cm)

Wei

gh

t (k

g)

2

4

6

8

10

12

14

16

18

20

22

2

4

6

8

10

12

14

16

18

20

22

45 50 55 60 65 70 75 80 85 90 95 100 105 110

15th

3rd

97th

50th

85th

Weight-for-length BOYS

Figure 5. WHO Child Growth Standards: Boys weight-for-length, birth to 2 years. Reprinted with permission.34

WHO Child Growth Standards

Birth to 2 years (percentiles)

Length (cm)

Wei

gh

t (k

g)

2

4

6

8

10

12

14

16

18

20

22

2

4

6

8

10

12

14

16

18

20

22

45 50 55 60 65 70 75 80 85 90 95 100 105 110

15th

3rd

97th

50th

85th

Weight-for-length GIRLS

Figure 6. WHO Child Growth Standards: Girls weight-for-length, birth to 2 years. Reprinted with permission.34

Clinical Growth Charts S95

WHO Child Growth Standards

BMI-for-age BOYSBirth to 2 years (percentiles)

Months

Age (completed months and years)

BM

I (kg

/m2 )

10

11

12

13

14

15

16

17

18

19

20

21

10

11

12

13

14

15

16

17

18

19

20

21

1 2 3 4 5 6 7 8 9 10 11 1 2 3 4 5 6 7 8 9 10 11

15th

3rd

97th

50th

85th

Figure 7. WHO Child Growth Standards: Boys BMI-for-age, birth to 2 years. Reprinted with permission.34

WHO Child Growth Standards

BMI-for-age GIRLSBirth to 2 years (percentiles)

Months

Age (completed months and years)

BM

I (kg

/m2 )

10

11

12

13

14

15

16

17

18

19

20

21

10

11

12

13

14

15

16

17

18

19

20

21

1 2 3 4 5 6 7 8 9 10 11 1 2 3 4 5 6 7 8 9 10 11

15th

3rd

97th

50th

85th

Figure 8. WHO Child Growth Standards: Girls BMI-for-age, birth to 2 years. Reprinted with permission.34

Appendix 5S96

WHO Child Growth Standards

Head circumference-for-age BOYSBirth to 5 years (percentiles)

Hea

d ci

rcum

fere

nce

(cm

)

Age (completed months and years)

3rd

15th

50th

85th

97th

Months 2 4 6 8 10 2 4 6 8 10 2 4 6 8 10 2 4 6 8 10 2 4 6 8 10Birth 1 year 2 years 3 years 4 years 5 years

32

34

36

38

40

42

44

46

48

50

52

54

32

34

36

38

40

42

44

46

48

50

52

54

Figure 9. WHO Child Growth Standards: Boys head circumference-for-age, birth to 5 years. Reprinted with permission.52

WHO Child Growth Standards

Head circumference-for-age GIRLSBirth to 5 years (percentiles)

Hea

d ci

rcum

fere

nce

(cm

)

Age (completed months and years)

3rd

15th

50th

85th

97th

Months 2 4 6 8 10 2 4 6 8 10 2 4 6 8 10 2 4 6 8 10 2 4 6 8 10Birth 1 year 2 years 3 years 4 years 5 years

32

34

36

38

40

42

44

46

48

50

52

32

34

36

38

40

42

44

46

48

50

52

Figure 10. WHO Child Growth Standards: Girls head circumference-for-age, birth to 5 years. Reprinted with permission.52

S

A

URE

Clinical Growth Charts S97

2 to 20 years: BoysStature Weight-for-age percentiles-for-age and

NAME

RECORD #

WEIGHT

WEIGHT

T

T

STATURE

lb

30

40

50

60

70

80

lb

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

kg10

15

20

25

30

35

80

85

90

95

100

105

110

115

120

125

130

135

140

145

150

155

160

cm

cm

150

155

160

165

170

175

180

185

190

kg10

15

20

25

30

35

105

45

50

55

60

65

70

75

80

85

90

95

100

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

12 13 14 15 16 17 18 19 20

AGE (YEARS)

AGE (YEARS)

40

90

75

50

25

10

90

75

50

25

10

113 4 5 6 7 8 9 10

97

3

97

3

62

42

44

46

48

60

58

52

54

56

in

30

32

34

36

38

40

50

74

76

72

70

68

66

64

62

60

inDate

Mother’s Stature Father’s Stature

Age Weight Stature BMI*

SOURCE: Developed b(2000).

y the National Center for Health Statistics in collaboration withthe National Center for Chronic Disease Prevention and Health Promotionhttp://www.cdc.gov/growthcharts

Published May 30, 2000 (modified 11/21/00).

Figure 11. CDC Clinical Growth Charts: Children 2 to 20 years, Boys stature-for-age and weight-for-age.

S

A

URE

Appendix 5S98

2 to 20 years: GirlsStature Weight-for-age percentiles-for-age and

NAME

RECORD #

WEIGHT

WEIGHT

T

T

STATURE

kg10

15

20

25

30

35

80

85

90

95

100

105

110

115

120

125

130

135

140

145

150

155

cm

150

155

160

165

170

175

180

185

190

kg10

15

20

25

30

35

105

45

50

55

60

65

70

75

80

85

90

95

100

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

12 13 14 15 16 17 18 19 20

AGE (YEARS)

AGE (YEARS)

40

160

cm 113 4 5 6 7 8 9 10

90

75

50

25

10

90

75

50

25

10

97

3

97

3

lb

30

40

50

60

70

80

lb

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

180

190

200

210

220

230

Date

Mother’s Stature Father’s Stature

Age Weight Stature BMI*

62

42

44

46

48

60

58

52

54

56

in

30

32

34

36

38

40

50

74

76

72

70

68

66

64

62

60

in

SOURCE: Developed b(2000).

y the National Center for Health Statistics in collaboration withthe National Center for Chronic Disease Prevention and Health Promotionhttp://www.cdc.gov/growthcharts

Published May 30, 2000 (modified 11/21/00).

Figure 12. CDC Clinical Growth Charts: Children 2 to 20 years, Girls stature-for-age and weight-for-age.

2B

P

Clinical Growth Charts S99

to 20 years: Boysody mass index-for-age percentiles

NAME

RECORD #

2 543 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

26

24

22

20

18

16

14

12

kg/m2

28

26

24

22

20

18

16

14

12

kg/m2

30

32

34

BMI

BMI

AGE (YEARS)

13

15

17

19

21

23

25

27

13

15

17

19

21

23

25

27

29

31

33

35

90

75

50

25

10

85

Date Age Weight Stature BMI* Comments

97

3

95

SOURCE: Developed b(2000).

y the National Center for Health Statistics in collaboration withthe National Center for Chronic Disease Prevention and Health Promotionhttp://www.cdc.gov/growthcharts

ublished May 30, 2000 (modified 10/16/00).

Figure 13. CDC Clinical Growth Charts: Children 2 to 20 years, Boys BMI-for-age.

2B

SP

Appendix 5S100

to 20 years: Girlsody mass index-for-age percentiles

NAME

RECORD #

2 543 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

26

24

22

20

18

16

14

12

kg/m2

28

26

24

22

20

18

16

14

12

kg/m2

30

32

34

BMI

BMI

AGE (YEARS)

13

15

17

19

21

23

25

27

13

15

17

19

21

23

25

27

29

31

33

35

Date Age Weight Stature BMI* Comments

90

85

75

50

10

25

97

3

95

OURCE: Developed b(2000).

y the National Center for Health Statistics in collaboration withthe National Center for Chronic Disease Prevention and Health Promotionhttp://www.cdc.gov/growthcharts

ublished May 30, 2000 (modified 10/16/00).

Figure 14. CDC Clinical Growth Charts: Children 2 to 20 years, Girls BMI-for-age.

dwbB

CamAfm

luekd

tte

ttGcpa

pAroict

A

APPENDIX 6: DESCRIPTION OF GUIDELINE DEVELOPMENT PROCESS

The KDOQI Clinical Practice Guideline on Nutrition and Children with CKD: Update 2008 waseveloped to incorporate new evidence and reference data that have emerged since the 2000 guidelinesere published and to harmonize the recommendations with those of other guidelines that have sinceeen issued. A scope of work was drafted by the Work Group Chairs and vetted by the NKF-KDOQIoard.In the spring of 2007, Bradley A. Warady, MD, and Donna Secker, PhD, RD, were appointed

o-Chairs of the Work Group. Work Group members were selected by the Co-Chairs for their clinicalnd research expertise in related areas of nutritional assessment and therapy in children with CKD. Theultidisciplinary group of pediatric nephrologists and dietitians included representatives from Northmerica, the United Kingdom, and Europe. Method guidance was provided by Katrin Uhlig, MD, MS

rom Tufts Center for Kidney Disease Guideline Development and Implementation, with additionalethods input provided by Ethan Balk, MD, MPH, also at the Center.The Work Group drafted narrative reviews based on their expertise and knowledge of the relevant

iterature. References were used to support the write-ups. Systematic literature review was notndertaken for any topic given the low-quality evidence known to exist in this field. This paucity ofvidence made it unlikely that an inclusive systematic search, to supplement what the experts alreadynew, would substantially improve the quality of the evidence base and the confidence that could beerived from it.The Work Group convened regularly by telephone and/or e-mail to refine the topics, recommenda-

ions, and supporting rationale. The methods consultant provided ongoing guidance and supporthroughout the guideline development process by participating in the Work Group’s teleconferences and-mail communications and reviewing guideline drafts.

The KDOQI approach regarding grading of the strength of the guideline recommendations followedhe approach adopted by KDIGO (see Tables 39 and 40). The strength of most guideline recommenda-ions was graded as C to signify that they were based predominantly on the expert judgment of the Workroup. Overall, given the heterogeneity and often unique circumstances of the disease conditions in

hildren with CKD and the great human cost of the disease in this age group, the Work Group adopted aerspective of erring in favor of issuing recommendations of potential use with lesser importancettached to potential monetary costs.

The public review process was initiated in September 2008. Participants were given 4 weeks torovide comments. Those who took part in the public review included members of the KDOQIdvisory Board and the NKF Council on Renal Nutrition; experts identified by the Work Group;

epresentatives from nephrology, dietetic, or other allied health–related professional associations;rganizations involved in the care of pediatric patients with kidney diseases; and professionalndividuals who requested to take part in the review process. Overall, all comments received werearefully considered by the Work Group Chairs and, with input from the Work Group, incorporated intohe final guideline as appropriate.

merican Journal of Kidney Diseases, Vol 53, No 3, Suppl 2 (March), 2009: pp S101-S104 S101

A

B

C

1

2

3

4

Appendix 6S102

Table 39. KDIGO Nomenclature and Description for Rating Guideline Recommendations

Strength of theRecommendation

Wording of theRecommendation Prerequisite Assumption Expectation

An intervention“should” bedone

The quality of the evidenceis “high” or additionalconsiderations supporta “strong”recommendation

Most well-informed individualswill make the same choice

The expectation is that therecommendation will befollowed unless thereare compelling reasonsto deviate from it in anindividual. A strongrecommendation mayform the basis for aclinical performancemeasure

An intervention“should beconsidered”

The quality of the evidenceis “high” or “moderate,”or additionalconsiderations supporta “moderate”recommendation

A majority of well informedindividuals will make thischoice, but a substantialminority may not

The expectation is that therecommendation will befollowed in the majorityof cases

An intervention is“suggested”

The quality of the evidenceis “moderate,” “low,” or“very low,” or additionalconsiderations supporta weakrecommendation basedpredominantly on expertjudgment

A majority of well-informedindividuals will consider thischoice

The expectation is thatconsideration will begiven to following therecommendation

Table 40. Checklist for Guideline Reporting for the Update of the KDOQI Pediatric Nutrition Guideline*

Topic Description Discussed in KDOQI Pediatric Nutrition Guideline

. Overview material Provide a structured abstract that includesthe guideline’s release date, status(original, revised, updated), and printand electronic sources.

See Executive Summary

. Focus Describe the primary disease/conditionand intervention/service/technologythat the guideline addresses. Indicateany alternative preventative,diagnostic, or therapeutic interventionsthat were considered duringdevelopment.

This guideline addresses the population of infants, children,and adolescents with CKD of congenital, hereditary,acquired, or metabolic etiology. The guideline considersevaluation of nutritional status and therapeuticinterventions, including enteral feeding, intradialyticparenteral nutrition, growth hormone therapy, andrestriction or supplementation of various macro- andmicronutrients.

. Goal Describe the goal that following theguideline is expected to achieve,including the rationale for developmentof a guideline on this topic.

This guideline is intended to assist the practitioner caringfor infants, children, and adolescents with CKD in theevaluation of their nutritional status, and in counselingand selecting nutrition therapies that are age- and CKDstage-appropriate to improve their survival, health, andquality of life.

. User/setting Describe the intended users of theguideline (eg, provider types, patients)and the settings in which the guidelineis intended to be used.

The intended audience for the guideline is:1) Practitioners: nephrologists, nephrology fellows,dietitians, nurse practitioners, nurses.2) Patients: infants, children and adolescents with CKDStages 2–5, 5D, and 1–5T and their relatives andfriends.3) Policy makers and those in related health fields.The settings for guideline implementation are in-patientor outpatient clinics, and satellite dialysis centers.

(Continued)

5

6

7

8

9

1

1

1

Description of Guideline Development Process S103

Table 40 (Cont’d). Checklist for Guideline Reporting for the Update of the KDOQI Pediatric Nutrition Guideline*

Topic Description Discussed in KDOQI Pediatric Nutrition Guideline

. Target population Describe the patient population eligible forguideline recommendations and list anyexclusion criteria.

Pediatric patients with CKD Stages 2–5, 5D, and 1–5TExcluded were those with minimal-change nephrotic

syndrome, or acute renal failure.. Developer Identify the organization(s) responsible for

guideline development and the names/credentials/potential conflicts of interestof individuals involved in the guideline’sdevelopment.

NKF-KDOQI nominated the Work Group chairs and themethods consultant. It provided administrative supportand organizational oversight.Names/credentials/potential conflicts of interest ofindividuals involved in the guideline’s development arepresented in the Work Group Biographical andDisclosure Information

. Funding source/sponsor Identify the funding source/sponsor anddescribe its role in developing and/orreporting the guideline. Disclosepotential conflict of interest.

NKF-KDOQI did not receive corporate support for thedevelopment of this guideline.

. Evidence collection Describe the methods used to search thescientific literature, including the rangeof dates and databases searched, andcriteria applied to filter the retrievedevidence.

The scope of work was to update the prior pediatricnutrition guidelines, published in 2000 as part of thelarger Clinical Practice Guidelines for Nutrition in ChronicRenal Failure. The Work Group drafted narrative reviewsbased on its expertise and knowledge of the literature inthe field and used references to support its write-up.Systematic literature review was not undertaken for anytopic given the low-quality evidence known to exist inthis field, which made it unlikely that an inclusivesystematic search to supplement what the expertsalready knew would substantially improve the quality ofthe evidence base. The Work Group convened regularlyby phone and/or e-mail to refine the topics,recommendations, and write-ups. Methodologicalguidance was provided by a staff member of the TuftsCenter for Kidney Disease Guideline Development andImplementation at Tufts Medical Center with expertise inguideline development and critical literature appraisal.

. Recommendationgrading criteria

Describe the criteria used to rate thequality of evidence that supports therecommendations and the system fordescribing the strength of therecommendations. Recommendationstrength communicates the importanceof adherence to a recommendation,and is based on both the quality of theevidence and the magnitude ofanticipated benefits and harm.

Formal grading of quality of studies or bodies of evidencewas not undertaken. The strength of therecommendations was graded in a 3-tiered gradingsystem, which was adopted for grading of guidelines byKDOQI leadership.

0. Method forsynthesizing evidence

Describe how evidence was used tocreate recommendations, eg, evidencetables, meta-analysis, decisionanalysis.

Narrative reviews by experts who could conduct their ownliterature searches.

1. Prerelease review Describe how the guideline developerreviewed and/or tested the guidelinesprior to release.

Guideline underwent internal and external review, with 68reviews received. Feedback was discussed initially in aconference call with the Co-Chairs, KDOQI Chair,Methods Consultants, and NKF-KDOQI GuidelineDevelopment Staff, followed by phone calls withindividual Work Group members. Feedback wasincorporated into the revised recommendations as theWork Group saw fit.

2. Update plan State whether or not there is a plan toupdate the guideline and, if applicable,expiration dates for this version of theguideline.

The need to update this guideline will be periodicallydetermined by the KDOQI Board. The needsassessment will include the review of new evidence thatwould change the content of the recommendations ortheir strength.

(Continued)

1

1

1

1

1

1

l

Appendix 6S104

Table 40 (Cont’d). Checklist for Guideline Reporting for the Update of the KDOQI Pediatric Nutrition Guideline*

Topic Description Discussed in KDOQI Pediatric Nutrition Guideline

3. Definitions Define unfamiliar terms and those critical tocorrect application of the guideline thatmight be subject to misinterpretation.

See Glossary of Definitions and List of Abbreviations andAcronyms.

4. Recommendationsand rationale

State the recommended action preciselyand the specific circumstances underwhich to perform it. Justify eachrecommendation by describing thelinkage between the recommendationand its supporting evidence. Indicatethe quality of evidence and therecommendation strength, based onthe criteria described in #9 above.

Recommendations are highlighted in each section and thesupporting rationale is provided in the narrative thatfollows. The strength of the recommendation is providedin parenthesis after each recommendation.

5. Potential benefits andharm

Describe anticipated benefits andpotential risks associated withimplementation of guidelinerecommendations.

The balance between estimated medical benefits andharm, and the certainty from the supporting evidence ,were considered in the formulation of the guidelinerecommendations. Implementation of the guidelinerequires skilled personnel and resources.

6. Patient preferences Describe the role of patient preferenceswhen a recommendation involves asubstantial element of personal choiceor values.

Less than “strong” recommendations inherently indicate agreater need for the practitioner to help each patient (orproxy) to arrive at a management decision consistentwith her or his values and preferences on behalf of thepatient.

7. Algorithm Provide (when appropriate) a graphicaldescription of the stages and decisionsin clinical care described by theguideline.

Tables, procedures for anthropometric measurements,copies of growth charts, and a list of resources forcalculating anthropometric z-scores are provided to helpwith implementation.

8. Implementationconsiderations

Describe anticipated barriers toapplication of the recommendations.Provide reference to any auxilliarydocuments for providers or patientsthat are intended to facilitateimplementation. Suggest review criteriafor measuring changes in care whenthe guideline is implemented.

Limitations to the recommendations were discussed andrecommendations were provided for future research.Comparison was made with other pediatric clinicalguidelines to highlight consensus or identify controversy.No review criteria were developed.

*This checklist was developed by the Conference on Guideline Standardization for Reporting Clinical Practice Guide-ines.522