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Oral Cimetidine Improves the Accuracy and Precision of Creatinine Clearance in Lupus Nephritis

Ronenn Roubenoff, MD, MHS; Helen Drew, CNMT; Martha Moyer, RN; Michelle Petri, MD; Quinn Whiting-O'Keefe, MD; and David B. Hellmann, MD
[+] Article, Author, and Disclosure Information

Grant Support: In part by NIH Grant RR00722 to the Outpatient Clinical Research Center. Dr. Roubenoff is supported by a Mellon Foundation Fellowship in Clinical Epidemiology. Placebo and Cimetidine pills and HPLC determinations were provided by SmithKline, and French Pharmaceuticals, Philadelphia, Pennsylvania.

Requests for Reprints: David B. Hellmann, MD, 1830 East Monument Street, Suite 9030, Baltimore, MD 21205.

Current Author Addresses: Dr. Roubenoff: USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111.

Drs. Hellmann and Petri, Ms. Moyer, and Ms. Drew: The Johns Hopkins Medical Institutions, 1830 East Monument Street, Baltimore, MD 21205.

Dr. Whiting-O'Keefe: 2202 Edgewood Road, Redwood City, CA 94062.

©1990 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1990;113(7):501-506. doi:10.7326/0003-4819-113-7-501
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Objective: To determine whether short-term use of oral Cimetidine improves the precision of creatinine clearance (CCr) 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 CCrs, were measured immediately after each 24-hour collection ("simultaneous study").

Measurements and Main Results: Use of Cimetidine improved the accuracy of CCr, as measured by the CDTPA-to-CCr ratio (1.07 [Cimetidine] compared with 1.33 [placebo]; P< 0.05). Cimetidine use also improved the precision of CCr (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 cimetidineaided CCr 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 (CCr) for determining GFR.





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