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A Practical Approach to Glomerular Filtration Rate Measurements: Creatinine Clearance Estimation Using Cimetidine

Address correspondence to Muhittin A. Serdar, M.D., Department of Clinical Biochemistry, Gulhane School of Medicine, Etlik-06018, Ankara, Turkey; tel 90 312 304 3308; fax 90 312 323 4923; e-mail: maserdar{at}hotmail.com

Determination of creatinine clearance (Ccr) is not a reliable indicator of glomerular filtration rate (GFR), owing to tubular secretion of creatinine. It has been reported that Ccr measurements can approximate true GFR after cimetidine (Ci) administration. In this study, GFR was estimated by Cockcroft and Gault’s equation (C_C-G) based on measurement of plasma creatinine, and Ccr was determined by the standard clearance equation using 4- and 24-hr urine samples (Ccr₄ and Ccr₂₄, respectively) in 17 patients and 10 healthy controls. After cimetidine administration (800 mg, 3 times daily), GFR values were recalculated at the same time periods (C_CiC-G, Ccr_Ci4 and Ccr_Ci24, respectively). The results were all compared to those obtained by the ^99mTc-DTPA protein-free double-sample method (C_DTPA), which is a reference method for GFR determination. The coefficient of variation (CV%) for Ccr₂₄/C_DTPA was high before cimetidine administration; Ccr₂₄ and Ccr_Ci24 values were significantly different from C_DTPA (CV 23.1%, Ccr₂₄/C_DTPA = 1.17, p 0.005; and CV 14.1%, Ccr_Ci24/C_DTPA = 0.92, p 0.006, respectively). Ccr₄ values obtained before cimetidine ingestion showed large variation and were significantly different from C_DTPA (CV 15.5%, Ccr₄/C_DTPA = 1.11, p 0.001). Ccr_Ci4 values after cimetidine were similar to C_DTPA (CV 6.9%, Ccr_Ci4/C_DTPA = 1.01, p 0.28). C_C-G estimates were higher before cimetidine intake (CV 12.4%, C_C-G/C_DTPA = 1.21, p <0.001), whereas C_CiC-G values were not significantly different from C_DTPA values (CV 7.0%, C_CiC-G/C_DTPA = 1.01, p 0.67). This study shows that GFR estimations by C_C-G, Ccr₄, Ccr₂₄, or Ccr_Ci24 are insufficiently reliable. On the other hand, C_CiC-G and Ccr_Ci4 results are acceptable for true GFR estimations.

Keywords: glomerular filtration rate, creatinine clearance, cimetidine, Cockcroft-Gault equation, renal function

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