Kidney Disease Research Updates
Winter 2009

Research News

Measurement of Kidney Function in Children Improved

A widely used formula to estimate kidney function in children with chronic kidney disease (CKD) has been revised to make it more precise, according to a study published on January 21 in the online edition of the Journal of the American Society of Nephrology. The study is based on data collected by the Chronic Kidney Disease in Children (CKiD) clinical study—the largest prospective cohort study of CKD in children in North America. CKiD is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health (NIH).

“This study illustrates the importance of our commitment to research on chronic kidney disease in children,” said NIDDK Director Griffin P. Rodgers, M.D, M.A.C.P. “As NIDDK-supported research discovers more accurate methods of diagnosing and monitoring biomedical conditions, our ability to treat those conditions, reduce suffering, and prolong life also continues to improve.”

Glomerular filtration rate (GFR), the flow rate of fluid through the tiny capillaries in the kidneys called glomeruli that filter waste materials out of the blood and into the urinary system, is the most useful indicator of kidney function. Measuring GFR, however, is costly, time-consuming, and difficult to perform at regular clinical office visits. As a result, different methods of estimating GFR using biochemical markers of kidney function have been developed.

Schwartz Formula

One of the methods for estimating GFR, the Schwartz formula, estimates GFR from an equation that uses serum creatinine—a waste product in the blood—and height. GFR estimates by this formula have been used as one of the enrollment criteria for the CKiD study, which assesses children with mild to moderate CKD.

The current study, led by George Schwartz, M.D., a professor in the Department of Pediatrics at the University of Rochester who originated the formula in the mid-1970s, used data from baseline CKiD visits of 349 children ages 1 to 16 to evaluate the existing GFR prediction equations.

The investigators compared the Schwartz formula with the current gold standard iohexol clearance method of determining true GFR, which measures the rate of disappearance of the x-ray dye iohexol from the blood, and found the Schwartz formula overestimated GFR. Because the iohexol method is only used every 2 years after the first two visits in the CKiD study, an accurate assessment of GFR is needed during the intervening annual visits.

After comparing various estimated GFR (eGFR) models using a testing data set of 168 children in the CKiD study, investigators found that a modified Schwartz formula using height, serum creatinine, cystatin C—a small protein expressed throughout the body—blood urea nitrogen, and biological sex came the closest to replicating the results of the iohexol method.

Use of eGFR allows investigators to describe the trajectory of declining kidney function and to adjust the dose of medications so they don’t become toxic to the kidneys. However, the investigators also point out that the revised formula may not be useful in the general pediatric population because the children they studied have reduced growth rates and delayed puberty.

“The relationship between estimated GFR and the biochemical markers may be different in this population than in a population with more normal kidney function and without poor skeletal growth,” said Schwartz. “Although we did not observe that our formula changed with puberty, other populations with more normal physique and health status should be examined to evaluate the estimated GFR for adolescents.”

Additional funding for the CKiD clinical study is provided by the NIH National Institute of Neurological Disorders and Stroke, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute.

More information about the CKiD study is available at www.ClinicalTrials.gov.

The National Kidney and Urologic Diseases Information Clearinghouse offers fact sheets about kidney disease in children at http://kidney.niddk.nih.gov/kudiseases/pubs/childkidneydiseases.

NIH Publication No. 09–4531
March 2009

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