Among children in the CKiD cohort 59% had underlying urological diagnoses. The etiologies causing CKD are similar to those previously reported in large CKD registries, including NAPRTCS and the ItalKid Project.1,5,16
In the CKiD study children with underlying urological disorders were predominantly male, and many had low birth weight and received ICU treatment after birth. Most patients were diagnosed early in life via ultrasound, were seen by a urologist before age 1 year and had undergone a urological procedure. These findings suggest that urologists in partnership with nephrologists have the opportunity to identify children at high risk for kidney disease progression and those comorbid conditions such as high blood pressure, low weight and short stature, which persist into childhood.
In our analysis of the subgroup with urological disorders in the CKiD cohort the newly developed CKiD estimating equations, eGFR and bedside GFR, had good correlation and low bias, indicating good agreement with the measured iohexol GFR, an improvement over prior estimating equations.10,11
The newly developed CKiD bedside GFR estimating equation is a simple, easily used tool that requires only serum creatinine and height, similar to the original Schwartz equation but with an updated coefficient. Thus, this equation can be used by the practicing urologist to assess level of kidney function in this high risk population.
There are also other markers of progression of kidney disease in addition to GFR. In the past nadir serum creatinine was found to be a predictor of future kidney function in children with structural causes of CKD, including posterior urethral valves, vesicoureteral reflux and prune belly syndrome, but was not as reliable a predictor among patients with cloacal malformations.17–20
However, following changing kidney function in children with serum creatinine alone can be misleading. While serum creatinine normally increases as children age, a small increase in serum creatinine (0.1 or 0.2 mg/dl) can portend a significant reduction in kidney function, especially if not accompanied by a corresponding increase in body size and muscle mass. Estimating GFR by calibrating creatinine to height using estimating equations can help mitigate this problem. Serum cystatin C and beta trace protein also hold promise for estimating kidney function in the future.21–23
A prior study of the CKiD cohort demonstrated that proteinuria is also associated with decreased GFR in addition to glomerular causes of CKD and nonwhite race.24
Although this study sample is large, this analysis has a number of limitations. It is cross-sectional in nature and cannot assess causes of decline in kidney function among study participants. Additionally as the formula was developed in the CKiD population (including children with urological and nonurological causes of kidney disease), its excellent agreement with measured GFR in this subgroup analysis is not surprising. However, the levels of agreement were essentially the same when the subset of subjects not used for equation development was analyzed (). Additional validation in a larger population of children with urological disease causing CKD may be useful to extend these inferences.
In our analyses of urological diagnosis subgroups another potential limitation was ascertainment of underlying diagnosis causing kidney disease. The attributed cause of kidney disease was physician reported or determined from chart review. However, only 1 primary diagnosis was recorded, and, therefore, it is possible that an individual participant could have multiple urological diagnoses (such as posterior urethral valves and vesicoureteral reflux). In addition, the distribution of causes of urological disease in the CKiD cohort might not be generalizable to the broader population of children with CKD. Selection bias may be present, as these participants were recruited from pediatric nephrology clinics in the United States and Canada. All cases already had compromised kidney function at study entry, and, therefore, likely represent more severe disease than all children with congenital abnormalities of the kidneys and urinary tract. Thus, these findings may have limited extrapolation to a general pediatric urology clinic population.
The new CKiD equations have been developed in a population of children with moderate to severe kidney disease and have not been prospectively validated in a population of children with normal or near normal kidney function and stature. When applied to a population based sample, estimates suggest that the new CKiD equations may underestimate kidney function among children with normal or mildly impaired kidney function.25
However, another study found good agreement of the new CKiD equations in a direct comparison with measured GFR.26
Despite these limitations, this study provides needed information about the characteristics of children with CKD due to urological diagnoses, and more accurate ways to estimate and monitor GFR among these children who are at risk for further decline in kidney function and ultimately ESRD requiring dialysis or transplant. The newly developed CKiD estimating equations may be used to estimate kidney function among children with moderate to severe renal impairment.