Cimetidine improves GFR-estimation by the Cockcroft and Gault formula

In some patients with renal disease 24-hour cimetidine aided creatinine clearances cannot equal GFR even after administration of the maximum daily dose of cimetidine. Short duration cimetidine aided creatinine clearances can equal GFR but are inconvenient for clinical use and can be inaccurate due to incomplete urine collection. We studied how accurately GFR can be estimated without the need to collect urine, by applying the Cockcroft and Gault formula (CCock) on a single plasma creatinine concentration, after oral administration of 3 x 800 mg cimetidine during the preceding 24 hours. GFR was measured as standard clearance, using continuous infusion of 125I-iothalamate. Nineteen patients with various renal diseases, plasma creatinine < 180 mumol/l and body mass index between 15 and 30 kg/m2 were included. After cimetidine administration, plasma creatinine values remained stable for 6 hours, despite rapidly decreasing plasma cimetidine values during the same period, in all 15 patients with GFR > 40 ml/min/1.73 m2. Tubular creatinine secretion was blocked completely in 14 of them. With cimetidine both accuracy and precision of the Cockcroft clearance improved: the mean (+/- SD) ratio of CCock to GFR decreased from 1.28 (+/- 0.21) to 0.98 (+/- 0.11) (p < 0.001) and the standard deviation of the difference (CCock-GFR) decreased from 9.23 to 7.07 ml/min/1.73 m2 (p < 0.05). With cimetidine the Cockcroft clearance correlated well with GFR (r = 0.974, p < 0.001) and this was as good as the correlation, between GFR and a 4-hour standard creatinine clearance (r = 0.972, p < 0.001). In conclusion, with a minimum of inconvenience, this method provides the clinician with accurate information on GFR for the outpatient follow-up of patients with a mild-to-moderate decrease in renal function, provided that no gross discrepancy between total bodyweight and muscle mass is present.