Accurate measurement of impaired glomerular filtration using single-dose oral cimetidine

To improve the validity of a timed creatinine clearance as a measure of glomerular filtration rate (GFR), we investigated whether a single 800-mg dose of oral cimetidine was sufficient to inhibit tubular secretion of creatinine (TScr). Forty-five 3-hour timed creatinine clearances (Cl-cr) with single 800-mg dose oral cimetidine (TCC) in 17 renal transplant recipients with marked renal function impairment (creatinine 2.0 to 7.1 mg/dL) were compared with simultaneous [I-125]-iothalamate GFR (Cl-iothal). For comparison, 13 timed Cl-cr without cimetidine (TC), and 36 24-hour Cl-cr were performed. The Too was the most accurate: the ratio (mean +/- SD) of TCC:Cl-iothal was 1.12 +/- 0.02, compared with 1.33 +/- 0.08 for Cl-cr:Cl-iothal, and 1.53 +/- 1.02 for TC:Cl-iothal. The difference between Cl-iothal and TCC was small over the range of GFRs tested (mean +/- 2 SD), 0.9 +/- 2.5 ml/min/1.73 ml. The intraclass correlation (R) for within-subject reproducibility of the TCC in five subjects was 0.8 (95% CI; 0.5, 0.9), and in 11 subjects who had at least three GFR determinations over 24 weeks, the TCC was as responsive to change in GFR as Cl-iothal. There was an inverse relationship between fractional excretion of cimetidine and GFR (r(2) = -0.70), suggesting increased tubular secretion of cimetidine with decreasing GFR. In conclusion, a single 800-mg oral dose of cimetidine was effective in inhibiting TScr such that the TCC was an accurate, reproducible, and responsive test of GFR. (C) 1996 by the National Kidney Foundation, Inc.