Oral cimetidine improves the accuracy and precision of creatinine clearance in lupus nephritis

Objective: To determine whether short-term use of oral cimetidine improves the precision of creatinine clearance (C_Cr) and reduces the overestimation of glomerular filtration rate (GFR) that occurs with this test in patients with lupus nephritis (because creatinine is secreted by injured renal tubular cells). Design: Double-blind, placebo-controlled, crossover clinical trial. Patients: Thirteen patients with lupus nephritis with mild renal insufficiency (mean serum creatinine, 230 μmol/L [2.6 mg/dL]; median, 106 μmol/L [1.2 mg/dL]). Interventions: Patients were given placebo or cimetidine tablets, 400 mg four times daily for 2 days, with ambulatory 24-hour urine collection during the second 24 hours ("outpatient study"). Simultaneous 4-hour technetium-99-diethylenetriamine penta-acetic acid (Tc⁹⁹-DTPA) and C_Crs were measured immediately after each 24-hour collection ("simultaneous study"). Measurements and Main Results: Use of cimetidine improved the accuracy of C_Cr, as measured by the C_DTPA-to-C_Cr ratio (1.07 [cimetidine] compared with 1.33 [placebo]; P < 0.05). Cimetidine use also improved the precision of C_Cr (P < 0.05). In addition, when compared with standard clinical estimators of GFR, creatinine clearance with cimetidine rendered the most precise estimates of GFR and explained more of the variation in GFR estimation than did any other method (R² = 0.78 compared with R² = 0.52 to 0.63). These effects were shown under both simultaneous and outpatient conditions. No side effects due to cimetidine occurred. Conclusions: In patients with lupus nephritis, the cimetidine-aided C_Cr offers a compromise between the precise and accurate but expensive and inconvenient research techniques (inulin, iothalamate, or DTPA clearances) and the grossly inaccurate and imprecise but convenient technique (C_Cr) for determining GFR.