increasing incidence of kidney stones in children evaluated in

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Increasing Incidence of Kidney Stones in Children Evaluated in theEmergency Department

David J. Sas, DO, MPH, Thomas C. Hulsey, MSPH, Sc.D, Ibrahim F. Shatat, MD, MSCR, and John K. Orak, MD

Objective To test the hypothesis that there is an increase in the incidence of childhood nephrolithiasis in the stateof South Carolina.Study design We analyzed demographic data from a statewide database on incidence of kidney stones fromemergency department data and financial charges. Data were compared with population data from the US Censusto control for population growth.Results There was a significant increase in the incidence of kidney stones in children between 1996 and 2007. Thegreatest rate of increase was seen in adolescents, pre-adolescents, and Caucasian children. Infants, toddlers, and

African-American children did not show significantly increased incidence in the period. Girls show a growing pre-dominance in our population. The amount of money charged for care of children with kidney stones has gone up >4-fold in our state.ConclusionThe incidence of kidney stone disease has risen dramatically in the state of South Carolina since1996. Further studies investigating potential contributing factors are needed to prevent this costly and painful con-

dition.(J Pediatr 2010;157:132-7).

Nephrolithiasis is rare in children. Recently, there have been anecdotal reports of an increasing incidence of childhoodnephrolithiasis (CN) in the popular press,1-3 although the only published data for American children supporting thesereports comes from 1 single-center study.4 If the incidence of nephrolithiasis in children is indeed rising, there is con-

siderable cause for concern becausenephrolithiasis is associated with significant pain and, in adult studies, elevated blood pres-sure,5 decreased renal function,6-8 and increased cost.9-11 Additionally, younger patients havea lower rate of spontaneouspassage of calculi and may be more likely to require invasive and costly surgical intervention.12

Kidney stones are formed by a process beginning with crystallization of solutes, followed by crystal growth and aggregation.They have varying composition with different salts; calcium oxalate is the most common type, followed by calcium phosphate.The remainder of stones in children are formed by magnesium ammonium phosphate (struvite), uric acid, and cystine. 13,14

Stones form in the context of a combination of elevated concentration of solute and promoters and insufficient concentrationof inhibitors.

Kidney stones are more common in the southeast United States, the so-called stone-belt.10,15-17 Although no definite causefor the increased incidence of stones in this region has been demonstrated, higher ambient temperatures and dietary factors

have been implicated. Our hypothesis is that the incidence of kidney stones in children in South Carolina is increasing. Inthis study, we used emergency department (ED) data as a proxy to determine an estimate for the incidence of kidney stonesin children and charges for care of children with nephrolithiasis in the state of South Carolina from 1996 to 2007. We analyzedthe data for demographic differences and trends in the incidence of nephrolithiasis in the study period.

Methods

Data on nephrolithiasis was obtained from the South Carolina All-Payer Uniform Billing Emergency Room Database main-

tained by the South Carolina State Office of Research and Statistics (Columbia, South Carolina), in which all ED visits inthe state are documented. State law mandates that this database be $99.5% accurate, and internal audits are routinely per-

formed to meet this requirement. Any patient seen in an ED with the International Classification of Diseases, Ninth Revision(ICD-9) code 592.0 (nephrolithiasis) or 592.9 (urolithiasis) between the ages of 0 and 18 years was included. Patients with mul-

tiple visits were counted only once. Data included patient age, sex, and race. Data on charges for care of children aged 0 to 18years with these same ICD-9 codes were obtained from the same source. No in-dividual identifying data were obtained. This study was approved by the institu-tional review board of the Medical University of South Carolina. From the Division of Pediatric Nephrology, Medical

University of South Carolina Childrens Hospital,Charleston, SC (D.S., I.S., J.O.); and Division of PediatricEpidemiology, Medical University of South Carolina,Charleston, SC (T.H.)

The authors declare no conflicts of interest.

0022-3476/$ - see front matter. Copyright 2010 Mosby Inc.

All rights reserved. 10.1016/j.jpeds.20 10.02.004

BMI Body mass index

CN Childhood nephrol ithiasis

ED Emergency department

132


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Population data were obtained from the United StatesCensus Bureau (www.census.gov).

Incidence was calculated on the basis of the number of

unique pediatric patients with nephrolithiasis per 100 000children. Statistical analysis was performed with c2 and rela-tive risk with SAS software version 9 (SAS Inc., Cary, NorthCarolina), with significance set atP< .05.

Results

From 1996 to 2007, nephrolithiasis was diagnosed in 1535

children in the state of South Carolina EDs with an overall in-cidence in the 12-year period of 12.0 per 100 000 children. In1996, the incidence of nephrolithiasis in children was 7.9 per100 000 children. This increased steadily to 18.5 per 100 000

(P< .0001) in 2007 (Figure 1). Comparing the first 3 years ofthe study period with the final 3 years, we observed that the 3-

year rate of nephrolithiasis for the period 1996 to 1998 was7.7, as compared with 17.2 for 2005 to 2007 (relative risk,2.2; 95% CI, 1.9-2.6;P< .0001).

To control for an increase in ED visits by children during

the study period, we compared the number of diagnoses ofnephrolithiasis each year with the number of ED visits. In1996, there were 8.1 diagnoses of nephrolithiasis per 100000 ED visits. After a decrease to 6.0 the following year,

this rose steadily to 13.9 diagnoses per 100 000 ED visits in2007 (P< .0001). African-American children were found to

use EDs 1.5 times more frequently than Caucasian children.The incidence of nephrolithiasis in male children was 8.0

per 100 000 versus 7.7 per 100 000 in female children in1996 (P= .86). The incidence increased at a faster rate in girls

between 1996 and 2007. In 2007, the incidence was 15.3 per

100 000 for boys versus 21.9 per 100 000 for girls (P= .01;Figure 2).

Considering the effect of race on kidney stone formation,the incidence has remained relatively flat (P = .36) inAfrican-American children with time (3.2 per 100 000 in

1996 versus 4.5 per 100 000 in 2007). In contrast, the inci-dence of nephrolithiasis in Caucasian children has increasedsignificantly (10.9 per 100 000 in 1996 versus 26.2 per 100 000in 2007,P< .0001;Figure 3). In 2005 to 2007, the 3-year ratefor Caucasian children was 24.1 as compared with 4.3 forAfrican-American children (P< .0001). Caucasian children

were 5.6 times (95% CI, 4.2-7.5) more likely to have stonesas compared with African-American children. In the past10 years, the stone rate for African-American children hasincreased 41%, as compared with 140% for Caucasianchildren. Races other than African-American or Caucasianare not represented significantly for nephrolithiasis in our

state, so these data are not shown.The rate of increase in the incidence of nephrolithiasis is

directly related to age (Figure 4). The highest increase in

incidence is seen in children aged 14 to 18 years, followedby children aged 9 to 13 years. Children


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increase compared with urban counties starting in 2003 andultimately achieved statistical significance in 2007. The inci-dence in rural counties in 2007 was 26.7 versus 17.4 per 100

000 children in urban counties. There was a trend towarda higher incidence in counties in the western half of the state.

The amount of healthcare dollars spent on nephrolithiasisis increasing. Adjusting for inflation by using the ConsumerPrice Index (expressed as 2007 dollars), total charges formanagement of nephrolithiasis in children has increased

from $3.4 million in the 1996 to 1998 period to $12.6 millionin the 2005 to 2007 period. There was also a significant shiftin the proportion of charges for nephrolithiasis from the in-patient setting to the outpatient setting. In 1996, inpatientcharges accounted for 70% of charges versus 30% for outpa-tient. By 2007, inpatient charges accounted for 39% and out-

patient for 61% of total charges for CN. Both charges andnumber of cases were higher in non-teaching institutions

compared with teaching institutions in 1996 (64% versus36%). This disparity increased slightly over the study period

to 76% and 24%, respectively. Private institutions accountedfor 80% of cases in 1996, compared with 20% in public insti-tutions. By 2007, private institutions accounted for 71% ofcases versus 29% in public institutions.

Discussion

Our data suggest a dramatic increase in the incidence ofnephrolithiasis in children in the state of South Carolina be-

tween 1996 and 2007. To our knowledge, this study repre-

sents the largest investigation to date into the incidence ofpediatric kidney stone disease.

The results of epidemiological studies of nephrolithiasisare mixed, and most have not included children. VanDer-

voort et al performed analysis of retrospective data from chil-dren with nephrolithiasis in their institution during 2

periods, 1994 to 1996 and 2003 to 2005.4 In the first period,they saw 7 children with nephrolithiasis, and they saw 61 inthe second period. Correcting for the number of new patientsseen in their nephrology clinic, this represents a 4.6-fold in-

crease in the 2 periods.Work by Lieske et al analyzed epidemiological nephroli-

thiasis data from a single county and focused primarily onadults, but also included graphs showing incidence data forchildren aged 0 to 19 years.18 Between 1970 and 2000, theyreported a slight increase in the incidence of nephrolithiasisin boys aged 0 to 19 years. For girls in the same age range

during the same period, they reported an initial increase in

nephrolithiasis incidence followed by a gradual decline. It isdifficult to compare this data with ours because the pediat-ric study population was approximately 30-fold smaller

than ours and the numeric data for children were not pro-vided.

Pearle et al analyzed national inpatient and outpatient datafor nephrolithiasis, but only reported inpatient length-of-stay data for children. Within the length-of-stay data, they re-port an increase in number of admissions for nephrolithiasis

in children between 1999 and 2001 from 461 to 619. In adults,they showed a decrease in the rate of inpatient visits for neph-rolithiasis, but an increase in the rate of outpatient visits and

an increase in expenditures for nephrolithiasis.

10

The shift in

Figure 3. Incidence of nephrolithiasis by race. In 1996, the

incidence of nephrolithiasis in African-American and Cauca-sian children was 3.2 and 10.9, respectively, versus 4.5 and26.2 in 2007. Incidence is expressed as number of uniquecases of nephrolithiasis per 100 000 children from each spe-cific demographic.

Figure 4. Incidence of nephrolithiasis by age. The incidence

of nephrolithiasis is increasing faster in older children thanyounger children. Incidence is expressed as number of uniquecases of nephrolithiasis per 100 000 children from each spe-cific demographic.

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134 Sas et al


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the management of nephrolithiasis in adults from inpatientto outpatient reported in this work is consistent with ourfindings in pediatrics, as are the increased costs.

In a study describing trends in hospital discharges fornephrolithiasis in adults, Scales et al showed no significantchange in population-adjusted hospital discharge rates be-tween 1997 and 2002.19 The rates for male patients decreasedsignificantly, and the rates for female patients increased. Al-though there remained a slight male predominance for neph-

rolithiasis by 2002, the gap between male and female patientsdecreased. In our study, we saw a slight female predomi-nance. Traditionally, male patients have had a higher inci-dence of nephrolithiasis.11,17,20 Our data and the data fromScales suggest a shift in sex-based predisposition for stone

formation.Our finding that the African-American race seems to be

protective of stone formation is supported by earlier stud-ies.10,17,21 African-American race also is somewhat protectiveagainst the increase in incidence observed. The finding thatAfrican-American children in South Carolina use EDs

more frequently than Caucasian children eliminates de-creased ED access as an explanation for decreased diagnosisof nephrolithiasis in African-American children. The reasonsfor this apparent resistance to stone formation are unknown,but are likely related to agenetic predisposition for lower uri-nary calcium excretion.22 Differences in dietary trends in

African-American and Caucasian children in South Carolinamay also play a role. Data from South Carolina show thatAfrican-American children drink less milk than Caucasianchildren and that both races are drinking less milk since

1999. The same data show that African-American childreneat more fruits and vegetables than Caucasian children.23

These data provide an intriguing area for investigation.Our finding that costs related to CN are increasing are con-

sistent with earlier adult studies, as are our data showinga shift from the inpatient setting to outpatient.9-11 This shiftis most likely a result of improved management (both med-

ical and surgical) in the outpatient setting.12,24-26

Why are we seeing an increase in childhood nephrolithia-sis? Rigorous genetic research is revealing important informa-tion aboutinherited metabolic characteristics predisposing tostones.27-33 However, our data reveal that the increasing inci-dence is most pronounced in school-aged and adolescent

children, suggesting a strong environmental component.

Obesity is a suspect, because of the increase in body massindex (BMI) in American children34-36 and, more specifi-cally, children in South Carolina37 concomitant with the in-crease in nephrolithiasis. Adult studies show a directcorrelation between risk of nephrolithiasis and BMI.38,39

Metabolic studies reveal altered urine chemistry dependenton BMI.40-43 Although the exact mechanism leading to stoneformation in obese individuals is unclear, it appears to be re-lated to an increase in chemical promoters of stone formationin relation to urine inhibitors.

There are fewer conclusive data in children about the effectof obesity on kidney stone formation and urine chemistry.

Eisner et al found that a higher BMI in children correlated

with increased supersaturation of calcium phosphate (in-creasing the likelihood of stone formation) but lower urine

oxalate levels.44 These findings are quite different from the

adult data and do not point to a clear association betweenobesity and nephrolithiasis in children. Investigation definingthe relationship between obesity and nephrolithiasis andcharacterizing urinary chemistry in obese children is needed.

A more likely suspect to account for the increase in CN isan increase in sodium intake. Excess sodium is associated

with hypercalciuria and increased risk for nephrolithia-sis.45-47 National Health and Nutrition Examination Surveydata show an increase in sodium intake in children from1971 to 1994, followed by a slight decrease in 2000.36 Amore recent publication reveals that approximately 92% of

American children have excessive sodium intake.48

Lower calcium intake in children is also a concern. Lower

calcium intake may contribute to a higher risk for nephroli-thiasis, although the full relationship between dietary calciumintake, absorption, and calciuria is quite complicated45,49,50

and beyond the scope of this discussion. Calcium intake is in-

adequate in older children and decreasing,23,36 and this maybe in part because milk consumption is being replaced byconsumption of sugary drinks.48,51 Other dietary factors in-cluding intake of protein, fructose,citrate,magnesium, andother elements may also play a role.46,50,52,53

Our study has several limitations. The source database is

limited to ED data and thus only provides an estimate ofthe true incidence. Not all children with kidney stones goto the ED; some children are treated at other outpatientclinics. Unfortunately, a similarly comprehensive all-payer

database for other outpatient visits is not available in ourstate, so we may have missed some individuals with CN,

thus underestimating the true incidence. Although we con-trolled for any increase in generalized use of EDs in our study,we recognize that other factors like increased referral to EDsfor symptoms consistent with kidney stones or increased sus-

picion, and thus investigation for kidney stones could haveaffected the data.

Additionally, improvements in imaging quality likely ac-count for a portion of the increased incidence of CN revealedin our study.

A database of any kind is dependent on appropriate data

input and, therefore, subject to reporting error. We believethis database to be reliable because it is directly linked to bill-

ing and internally audited for accuracy. The Office of Re-search and Statistics (which maintains the database) does

not allow release of identifying data that would be requiredfor further validation. Another limitation is that this database

does not provide us access to any clinical information, mak-ing further investigation into associated patient characteris-tics impossible. Finally, because this study included onlythe population of South Carolina, it is not certain that these

results represent CN in other regions.The difficulty in pursuing scientifically sound research in

children correlating dietary intake to nephrolithiasis lies inthe inability to reliably control intake in the outpatient set-

ting. Although the feasibility of definitively concluding

July 2010 ORIGINAL ARTICLES

Increasing Incidence of Kidney Stones in Children Evaluated in the Emergency Department 135


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a cause and effect relationship between environmental anddietary determinants of risk for CN is in question, other mo-dalities exist to help elucidate the metabolic mechanisms un-

derlying kidney stone disease. The study of genetics andurinary proteomics has emerged as a promising method forelucidating the molecular underpinnings of crystallizationand stone formation.28,32,54,62 Embarking on research en-deavors using newer techniques and continuing to examineenvironmental risk factors for stone formation will lead, we

hope, to a more sophisticated and successful approach tothe growing challenge of nephrolithiasis in children.

The incidence of nephrolithiasis in children and the costburden on the healthcare system is increasing in the state

of South Carolina. Because of this dramatic rise, there is anurgent need to investigate potential contributing factors pro-moting stone formation in children so that appropriate pre-ventative measures can be used. n

Submitted for publication Sep 3, 2009; last revision received Dec 28, 2009;

accepted Feb 3, 2010.

Reprint requests: David J. Sas, DO, MPH, Assistant Professor, Dept ofPediatrics, Division of Pediatric Nephrology, Medical University of South

Carolina, 96 Jonathan Lucas St, 316 CSB, MSC 608, Charleston, SC 29425-

6080. E-mail:[email protected].

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