Estimation of Renal Function

Renal function is usually assessed through calculation of glomerular filtration rate (GFR). The reference method for estimating GFR is inulin clearance. Inulin is an inert polysaccharide cleared exclusively by glomerular filtration. The method includes constant intravenous infusion of inulin and timed collection of urine and is not practical for routine clinical purposes. A number of alternative methods have been developed for estimation of GFR. Many involve collection of urine and may give inaccurate results unless collection of urine is complete, including complete emptying of the bladder. Several methods to determine the plasma clearance of a suitable exogenous marker have been developed. These include radionuclides such as 51Cr-EDTA and 99mTc-DTPA (diethylenetriaminepentaacetic acid) [21]. Although these methods are accurate, the requirement of radiolabeled tracers complicates the procedure (complicated handling, storage, and disposal of waste) and excludes certain patients, such as pregnant women. Alternative nonlabel filtration markers include the exogenous markers iothalamate and iohexol [22, 23] or endogenous markers such as Cystacin C [22] and, most importantly, creatinine [24].

GFR can be estimated by calculating creatinine clearance (CLcr) utilizing the serum creatinine concentration (Scr) and other patient characteristics such as bodyweight, age, gender, and height. All methods for estimating CLcr from Scr are simple, but are limited. Prediction of CLcr will not be accurate unless renal function and serum creatinine are at steady state and is not accurate in patients with unusually low or high muscle mass, in patients with marked obesity or ascites [24], or in patients with liver disease [25]. Moreover, creatinine is not exclusively filtered, but also subject to tubular secretion. Thus, GFR is overestimated by CLcr. This is especially evident in severe renal impairment. Creatinine clearance can also be determined from serum creatinine concentration and urinary excretion of creatinine. With this method, some of the drawbacks of using Scr can be avoided. The results are more accurate than estimation from Scr alone if complete collection of urine, including complete emptying of the bladder, can be obtained.

Given the limitations of using CLcr as a measure of renal function, more accurate methods for measuring renal function, such as 51Cr-EDTA, iothalamate or iohexol, should be considered in clinical studies evaluating the influence of renal function on the pharmacokinetics of new drugs.

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