A practical approach to glomerular filtration rate measurements: creatinine clearance estimation using cimetidine

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), CcrCi4 and CcrCi24, 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 CcrCi24 values were significantly different from C(DTPA) (CV 23.1%, Ccr24/C(DTPA) = 1.17, p 0.005; and CV 14.1%, CcrCi24/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). CcrCi4 values after cimetidine were similar to CDTPA (CV 6.9%, CcrCi4/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 CcrCi24 are insufficiently reliable. On the other hand, C(CiC-G) and CcrCi4 results are acceptable for true GFR estimations.