Determination of early or subtle changes in glomerular filtration rate (GFR) is essential in the management of patients with many renal diseases. GFR is used in making decisions about medical regimens, monitoring disease progression, and initiating and monitoring drug therapy. Inulin clearance is the gold standard procedure used to determine GFR. Creatinine clearance measurements are used to estimate GFR, since inulin studies are expensive and difficult to perform. However, creatinine clearance over-predicts GFR because creatinine is also secreted in the renal tubules. Therefore, creatinine clearance measurements have less than optimal sensitivity at detecting changes in GFR. Cimetidine is an anti-ulcer agent that also blocks the tubular secretion of creatinine; thus creatinine acts like inulin. Cimetidine-aided creatinine clearance studies in adults show an excellent correlation with inulin clearance and GFR. Therefore, we propose to study the hypothesis that a cimetidine-aided creatinine clearance approximates inulin clearance and can be used to assess GFR in children. We hope to enroll patients who are already enrolled in the hypoparathyroid and cystinosis studies at MR. These patients are already undergoing two 24-hour creatinine clearance studies. Patients will be asked to undergo a pre-treatment with cimetidine before the second 24-hour creatinine clearance and then have an inulin clearance study performed. To detect a 20% difference between the two creatinine clearance regimens with 80% power and a two-tailed significance level of 0.05, 8 available patients need to be enrolled. Standard deviation is estimate at 20%. With the data collected, we will also identify a ratio of cimetidine-aided creatinine clearance to inulin clearance and identify the precision of that estimate. We will also establish the confidence interval around that estimate. We request enrollment of up to 14 patients in anticipation of study attrition.
