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

The accuracy of the standard 24-hour creatinine clearance (C(Cr)) measurement of glomerular filtration rate (GFR) in renal transplant recipients is limited because tubular secretion of creatinine causes C(Cr) to overestimate GFR. We investigated whether cimetidine, a know blocker of tubular creatinine secretion, improves the accuracy and precision of C(Cr) 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 C(Cr) and inulin clearance (C(In)) 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 C(Cr) measurements. Cimetidine improved the accuracy of C(Cr) as a measure of GFR, as indicated by a reduction in the ratio of simultaneously measured C(Cr)/C(In) from 1.50 ± 0.55 to 1.23 ± 0.29 (mean + SD) after 3 days (p<0.01). The precision of the C(Cr) was also improved by cimetidine, as indicated by a reduction in the coefficient of variation of the C(Cr)/C(In) ratio from 0.36 to 0.23. The ratio of the 24-hour C(Cr)/C(In) (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 C(Cr) 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 C(Cr) determinations.