The Schwartz formula was devised in the mid-1970s to estimate GFR in children. Recent data suggest that this formula currently overestimates GFR as measured by plasma disappearance of iohexol, likely a result of a change in methods used to measure creatinine. Here, we developed equations to estimate GFR using data from the baseline visits of 349 children (aged 1 to 16 yr) in the Chronic Kidney Disease in Children (CKiD) cohort. Median iohexol-GFR (iGFR) was 41.3 ml/min per 1.73 m 2 (interquartile range 32.0 to 51.7), and median serum creatinine was 1.3 mg/dl. We performed linear regression analyses assessing precision, goodness of fit, and accuracy to develop improvements in the GFR estimating formula, which was based on height, serum creatinine, cystatin C, blood urea nitrogen, and gender. This formula yielded 87.7% of estimated GFR within 30% of the iGFR, and 45.6% within 10%. In a test set of 168 CKiD patients at 1 yr of follow-up, this formula compared favorably with previously published estimating equations for children. Furthermore, with height measured in cm, a bedside calculation of 0.413*(height/serum creatinine), provides a good approximation to the estimated GFR formula. Additional studies of children with higher GFR are needed to validate these formulas for use in screening all children for CKD.
GFR is the best indicator of renal function in children and adolescents and is critical for diagnosing acute and chronic kidney impairment, intervening early to prevent end-stage renal failure, prescribing nephrotoxic drugs and drugs cleared by a failing kidney, and monitoring for side effects of medications. Renal inulin clearance was the gold standard for GFR but is compromised by lack of availability, difficult assays, and problems of collecting timed urine samples, especially in children with vesicoureteral reflux or bladder dysfunction. Creatinine clearance-based estimates of GFR are often used in pediatrics. The addition of cimetidine to eliminate creatinine secretion permits accurate measurement of GFR in those who can completely empty their bladders to provide timed urine collections. Radioisotopes are used in plasma disappearance GFR determinations; however, these are not ideal for use in children, especially for repeated studies. The plasma disappearance of iohexol serves as a promising alternative GFR marker, because it is safe and not radioactive, easily measured, not metabolized or transported by the kidney, and excreted primarily by glomerular filtration. GFR estimating equations, based on serum concentrations of creatinine or cystatin C, are popular clinically and in research studies. Efforts are ongoing to improve these estimating equations for children and make the results readily available to clinicians obtaining standard chemistry profiles, as is being done for adults. However, at this time, there is no dependable substitute for an accurately determined GFR, and iohexol plasma disappearance offers the best combination of safety, accuracy, and reproducible precision.
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