Reevaluation of Formulas for Predicting Creatinine Clearance in Adults and Children, Using Compensated Creatinine Methods

In clinical practice, glomerular filtration rate (GFR) is the most important marker for evaluation of renal function (1). Dosages of drugs that are eliminated by glomerular filtration are often based on GFR. At present, the most reliable methods for accurate assessment of overall GFR require intravenous administration of exogenous compounds and are both cumbersome and expensive. In clinical practice, creatinine clearance (CrCl) is widely accepted as a simple measure of GFR. However, CrCl systematically overestimates GFR because creatinine is freely filtered by the glomerulus and is also secreted by the proximal tubule. In the earliest methods, serum creatinine was assayed by the Jaffe reaction after deproteinization, eliminating the pseudo-chromogen effect of proteins (2). Similarly, the first automated methods used dialysis membranes to prevent interference from plasma proteins. Today, however, analyzers use undiluted serum and plasma, making them subject to the so-called “protein error” (3). This produces a positive difference of ∼27 μmol/L creatinine compared with HPLC methods (4)(5)(6)(7). Because urine contains relatively little or no protein, the protein error affects only creatinine determinations in serum. Therefore, CrCl is underestimated when creatinine methods affected by protein error are used. This underestimation has been stated to be compensated by the overestimation attributable to tubular secretion of creatinine. However, studies confirming this statement are lacking.In compensated Jaffe methods, the values assigned to the calibrator set point are adjusted to minimize the pseudo-creatinine contribution of proteins. The result is that compensated methods produce lower creatinine values. Alternatively, the protein error can be avoided by use of enzymatic creatinine methods. Collection of timed urine for CrCl is often a major source of error; therefore, simple formulas have been introduced to estimate GFR based on serum creatinine concentration, age, gender, body weight, and body length (8)(9) …