Improvement in the accuracy and precision of creatinine clearance as a measure of glomerular filtration rate with oral cimetidine in renal transplant recipients

Abstract

The accuracy of the standard 24‐hour creatinine clearance (CCr) measurement of glomerular filtration rate (GFR) in renal transplant recipients is limited because tubular secretion of creatinine causes CCr to overestimate GFR. We investigated whether cimetidine, a know blocker of tubular creatinine secretion, improves the accuracy and precision of CCr as a measure of GFR. Cimetidine (600–1200 mg/day p.o.) was administered for 3 days to 16 renal transplant recipients who had different levels of allograft function. The CCr and inulin clearance (CIn) were simultaneously measured before the first dose and after the last dose of cimetidine. Cumulative urine collections were obtained daily before, during, and for 3 days after cimetidine administration to evaluate the effects of cimetidine on creatinine excretion and standard CCr measurements. Cimetidine improved the accuracy of CCr as a measure of GFR. as indicated by a reduction in the ratio of simultaneously measured CCr,/CIn from 1.50 ± 0.55 to 1.23±0.29 (mean±SD) after 3 days (p<0.01). The precision of the CCr was also improved by cimetidine. as indicated by a reduction in the coefficient of variation of the CCr/CIn ratio from 0.36 to 0.23. The ratio of the 24‐hour CCr/CIn (not measured simultaneously) was reduced from 1.13 + 0.25 to 0.97±0.14 after only 1 day on cimetidine therapy (p<0.01). Although the cimetidine‐modified CCr may not completely eliminate the problem of GFR overestimation, it offers a practical measure of renal allograft function that may be more accurate and precise than currently used serum creatinine and CCr determinations.