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Preventing and Managing Chronic Kidney

Disease in Children

Constantinos J. Stefanidis, MD, PhD

“P & A Kyriakou” Children’s Hospital, Athens, Greece

Defining CKD

Preventing CKD progression

Managing complications

Defining CKD

Kidney Disease Outcomes Quality Initiative (KDOQI)

working group of the National Kidney Foundation (NKF)

defined chronic kidney disease as:

• evidence of structural or functional kidney

abnormalities (abnormal urinalysis, imaging studies,

or histology)

• that persist for at least 3 months

• with or without a decreased glomerular filtration rate

(GFR <60 mL/min per 1.73 m2)

K/DOQI clinical practice guidelines for CKD Am J Kidney Dis. 2002

Glomerular

capillaries

Bowman’s capsule

Glomerulus

Glomerular filtration rate (GFR)

Bowman’s

capsule

Glomerular

capillaries

GFR

170 L / 24hrs/1.73 m2

120 mL/min/1.73 m2


GFR

170 L / 24hrs/1.73 m2

120 mL/min/1.73 m2

1.5 L /24hrs/1.73 m2


GFR

NKF-K/DOQI Classification of the Stages of CKD

Stage

GFR /1.73 m2

1

≥90

Kidney damage* with

normal or increased GFR

2

60–89

Kidney damage with

mild reduction of GFR

Description


NKF-K/DOQI Classification of the Stages of CKD

Stage

GFR /1.73 m2

1

≥90

Kidney damage with

normal or increased GFR

2

60–89

Kidney damage with

mild reduction of GFR

3

30–59

moderate reduction of GFR

4

15–29

severe reduction of GFR

5

<15

(or dialysis)

Kidney failure

Description


Defining kidney damage in CKD

1. Urine sediment abnormalities

2. Electrolyte and other abnormalities due to tubular

disorders.

3. Imaging abnormalities. Patients with significant

structural abnormalities persisting for > 3 months.

4. Pathologic abnormalities in kidney tissue obtained by

biopsy.

5. History of kidney transplantation.

KDIGO 2012 Clinical Practice Guideline Kidney Intern 2013`

Defining CKD: determine the cause

In any child with GFR<60 ml/min/1.73m2 or more than 1 SD below expected for their age and sex

or with markers of kidney damage

Consider:

• a complete review of their past history

• previous measurement or estimate of renal function

KDIGO 2012 Clinical Practice Guideline Kidney Intern 2013




Consider:



• prenatal history, drug exposures of fetus or mother

• genetic conditions, coincident organ abnormalities





Consider:



• prenatal history, drug exposures of fetus or mother

• genetic conditions, coincident organ abnormalities

• physical examination

• fetal and post-natal laboratory measures

(amniotic fluid, pre- and post-natal imaging, placenta)


Stages of CKD (KDIGO 2012)

KDIGO 2012 Clinical Practice Guideline Kidney Intern 2013`

Defining CKD in children < 2 years

K/DOQI clinical practice guidelines for CKD Am J Kidney Dis. Feb 2002

This definition is not applicable to children < 2 years,

because they normally have a low GFR.

The criteria for duration >3 months does not apply to

newborns or infants <3 months of age.

GFR > 1 SD below the mean (> -1 SDS): normal

GFR < 1 SD below the mean: moderately reduced GFR

GFR < 2 SD below the mean: severely reduced GFR

GFR in children < 2 years

Piepsz A, et al. Eur J Nucl Med Mol Imaging, 2006

http://cjasn.asnjournals.org/content/4/11/1832.full

moderately

Reduced GFR

severely Age months

Mean Mean -1SD Mean -2SD

<1 50 40 30

1.1 to 3.5 60 50 35

3.6 - 8 70 60 45

8.1 - 12 80 65 50

12.1 - 24 90 75 55










• Estimated GFR (eGFR)

• Creatinine clearance (CCr)

• Isotopic measurement (iGFR)

• Inulin clearance

• Ιohexol clearance and urinary protein

Chronic Kidney Disease in Children (CKiD) trial

Equations to Estimate GFR in Children with CKD

Updated Schwartz “bedside” formula:

eGFR = 0.41 x height (cm) / Scr (mg/dl)

25% reduction from the previous formula

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653687/

GJ Schwartz et al, CJ Am Soc Nephrol. 2009

eGFR = 36.5 x height (cm) / Scr (μmol/L)

enzymatic creatinine determinations

Chronic Kidney Disease in Children (CKiD) trial




Equations to Estimate GFR in Children with CKD

Updated Schwartz bedsite formula:


GJ Schwartz et al,J Am Soc Nephrol. 2009

K = 0.41




Cystatin C to estimate GFR in Children with CKD

The sensitivity of s-CysC for detecting impaired GFR in

pediatric patients seems superior to that of plasma

creatinine, especially in selected populations of children

with low muscle mass.

To answer the question of superiority of s-CysC in the

‘creatinine-blind’ area, studies excluding children with low

GFR values need to be performed.

Andersen TB et al., Pediatr Nephrol 2009



Defining CKD

Prevention of CKD progression


We recommend that in children with CKD, BP-lowering

treatment is started when BP is consistently above the

90th percentile for age, sex, and height. (1C)

We suggest that in children with CKD (particularly those

with proteinuria), BP is lowered to consistently

achieve systolic and diastolic readings less than or

equal to the 50th percentile for age, sex, and height,

(2D)

Prevention of CKD progression


We suggest that an ARB or ACE-I be used in children

with CKD in whom treatment with BP-lowering drugs is

indicated, irrespective of the level of proteinuria. (2D)

Prevalence of CKD complications


ESCAPE trial

ESCAPE trial

385 children of age 3-18 years GFR 15-80 ml/min/1.73m2

Patients were randomly assigned to:

Intensified BP control

(with a target 24-hour mean arterial pressure <50th percentile)

or

Conventional BP control

(mean arterial pressure in the 50th to 95th percentile)

Ramipril 6 mg/m2/day

ESCAPE trial

Age (years)

0 2 4 6 8 10 12 14 16

0

10

20

30

40

50

60

70

80

Renal hypoplasia-dysplasia

CKD and risk of AKI


We recommend that all people with CKD are considered

to be at increased risk of AKI. (1A)

People with CKD, should be followed for management

when undergoing investigation and procedures that are

likely to increase the risk of AKI. (Not Graded)



Defining CKD

How does CKD present?

Asymptomatic Disease

Especially early despite the

accumulation of harmful metabolites

Incidental finding of urine abnormalities or

raised creatinine

Complications of CKD

Polyuria

Nocturia

Oedema

LVH

Hypertension

Seizures

Confursion

Coma

CKD-MBD

Muscle weackness

Bone pain

Fractures

Anemia

Pallor

GI tract

Anorexia

Nausea

Vomiting

Diarrhea

Endocrine

Amenorrhoea

Growth failure

Malnutrition

Complications of CKD: Poor growth

Polyuria

Nocturia

Sodium loss

CKD-MBD

Muscle weackness

Bone pain

Fractures

Anemia

Pallor

Endocrine

Amenorrhoea

Growth failure

GI tract

Anorexia

Nausea

Vomiting

Diarrhea

Malnutrition

Metabolic acidosis

0

-1.0

-2.0

-3.0

-4.0

0.5 1.5 2.5 3.5 4.5 5.5 6.5 7.5 8.5 9.5 10.5 11.5 12.5

Age, years

63

75 78

75 71

68 62

59 55 47

44 43 42

40

34

27 24

20 19 18 15

10 7

5

2

Kari et al. Kidney Int 2000

Heig

ht

SD

S

Retrospective analysis from GOS

81 children <6 months of life

GFR < 20 ml/min/1.73m2

81%: enterally fed for 0.1 to 6.8 years

Growth failure in Children with Chronic Kidney Disease (4C)

Doyon et al. PLOSone 2015

Salt intake


We recommend restriction of sodium intake for children

with CKD who have hypertension or prehypertension

(1C)

We recommend supplemental free water and sodium s

for children with CKD and polyuria to avoid chronic

intravascular depletion and to promote optimal growth.

(1C)

Metabolic acidosis


We suggest that in people with CKD and serum

bicarbonate concentrations < 22mmol/l treatment with

oral bicarbonate supplementation be given to maintain

serum bicarbonate within the normal range, unless

contraindicated. (2B)

Metabolic acidosis and statural growth


The Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C)

There was a negative effects of metabolic acidosis on

height SDS.

Chronic Kidney Disease – Mineral Bone Disorder (CKD – MBD)

A systemic disorder of bone and

mineral metabolism due to CKD

manifested by either one or a

combination of the following:

– Abnormalities of Ca, P, PTH,

or vit. D metabolism








– Abnormalities in bone

turnover, mineralization,

volume, linear growth, or

strength








– Abnormalities in bone

turnover, mineralization,

volume, linear growth, or

strength

– Vascular or other soft tissue

calcification

Calcitriol, PTH and stages of CKD

The Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C)


Normal 25-OH D3 Attenuate Renal Failure Progression in Children with CKD

Shroff R JASN 2015 EPUB

CKD – behavioral and learning problems

http://www.niddk.nih.gov/health-information/health-topics/kidney-disease/facing-the-

challenges-of-chronic-kidney-disease-in-children/Pages/facts.aspx`

Children with (CKD) may have a negative self-image

and may have relationship problems with family

members.

The condition can lead to behavior problems and

make participating in school and extracurricular

activities more difficult.

Children with CKD may have trouble concentrating

CKD can cause learning problems

Multiprofessional team

Take home messages

Early diagnosis and treatment of kidney damage

Take home messages

Early diagnosis and treatment of renal damage

Effective management to slow progression of CKD

Take home messages

Early diagnosis and treatment of renal damage.

Effective management to slow progression of CKD.

Appropriate treatment of complications

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