Performance of the Cockcroft-Gault,MDRD, and New CKD-EPI Formulas in Relation to GFR,Age, and Body Size

Background and objectives: We compared the estimations of Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations to a gold standard GFR measurement using ¹²⁵I-iothalamate, within strata of GFR, gender, age, body weight, and body mass index (BMI).Design, setting, participants, & measurements: For people who previously underwent a GFR measurement, bias, precision, and accuracies between measured and estimated kidney functions were calculated within strata of the variables. The relation between the absolute bias and the variables was tested with linear regression analysis.Results: Overall (n = 271, 44% male, mean measured GFR 72.6 ml/min per 1.73 m² [SD 30.4 ml/min per 1.73 m²]), mean bias was smallest for MDRD (P < 0.01). CKD-EPI had highest accuracy (P < 0.01 compared with Cockcroft-Gault), which did not differ from MDRD (P = 0.14). The absolute bias of all formulas was related to age. For MDRD and CKD-EPI, absolute bias was also related to the GFR; for Cockcroft-Gault, it was related to body weight and BMI as well. In all extreme subgroups, MDRD and CKD-EPI provided highest accuracies.Conclusions: The absolute bias of all formulas is influenced by age; CKD-EPI and MDRD are also influenced by GFR. Cockcroft-Gault is additionally influenced by body weight and BMI. In general, CKD-EPI gives the best estimation of GFR, although its accuracy is close to that of the MDRD.With the increasing incidence of kidney dysfunction, the use of formulas to estimate kidney function is implemented more frequently in clinical practice (1). The most frequently used formulas are the Cockcroft-Gault and (abbreviated) Modification of Diet in Renal Disease (MDRD) equations (2). The Cockcroft-Gault equation estimates clearance of creatinine (3), whereas the MDRD estimates GFR (2). At present, for subgroups of people who are old, underweight, or overweight, no clear-cut advice exists regarding which formula is best used for optimal estimation of kidney function. Both Cockcroft-Gault and abbreviated MDRD have been compared in the same population against a gold standard method for estimating GFR (4–8). These studies show conflicting results because of different study populations, different gold standard GFR measurements, and differences in creatinine assay calibration (9). Furthermore, the recently developed Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula has not been validated yet, outside pf the original publication (10); therefore, a pragmatic study to evaluate the most often used formulas, in a study population in which a GFR measurement is requested, is needed. Furthermore, these formulas need to be compared with an excellent gold standard GFR measurement.In our center, GFR is measured by a method that can be considered the gold standard in the absence of bladder catheterization, for clinical reasons with a continuous infusion of ¹²⁵I-iothalamate (11–13). ¹³¹I-hippuran is added to correct for inaccurate urine collections without using a bladder catheter to optimize GFR measurement further (13). The aim of this study was to assess the agreement between kidney function as estimated by the Cockcroft-Gault, MDRD, and CKD-EPI equations and the GFR as measured by a gold standard method using ¹²⁵I-iothalamate. To examine whether the agreement is influenced by the level of GFR, gender, age, body weight, and body mass index (BMI), we also analyzed the agreement within clinically relevant strata of these variables.