Influence of Body Weight on the Performance of Glomerular Filtration Rate Estimators in Subjects With Type 2 Diabetes RICHARD A. CHUDLEIGH, MRCP 1 GARETH DUNSEATH, MPHIL 1 RAJESH PETER, MRCP 1 JOHN N. HARVEY, MD, FRCP 2 RICHARD L. OLLERTON, PHD 3 STEVE LUZIO, MD 1 DAVID R. OWENS, MD, FRCP 1 T he American Diabetes Association recommends estimation of glomer- ular filtration rate (GFR) (1) by ei- ther the Cockcroft-Gault (2) or the Modification of Diet in Renal Disease (MDRD) (3) equation in all patients with diabetes. The implication is that these equations provide similar results. Body weight is a numerator in the Cockcroft- Gault equation; however, it is absent from the MDRD equation. This may explain some of the difference in the ability of these equations to estimate GFR in pa- tients with type 2 diabetes, over 80% of whom are obese (4), and may lead to dis- crepancies in reporting of chronic kidney disease stage (5). Our study was designed to identify whether body weight may ex- plain variability in performance between the Cockcroft-Gault and MDRD equa- tions in patients newly diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS — The study population consisted of 293 subjects newly diag- nosed with type 2 diabetes; 96% were Caucasian and the remainder of South Asian origin. No African-American sub- jects were included. Following an overnight fast, anthro- pometric and biochemical measurements were made. Subjects were intravenously cannulated, and 1 MBq 51 Cr-EDTA was administered at 0 min, with further blood sampling at 44, 120, 180, and 240 min. The 51 Cr-EDTA plasma clearance method for GFR measurement, corrected for body surface area (BSA), has been vali- dated previously (6). This allows estimation of a two-compartment model. A close cor- relation exists between total plasma clear- ance of 51 Cr-EDTA and inulin clearance determined by the classical technique (7). Creatinine levels were determined us- ing the OCD (Johnson & Johnson) dry slide system on the Vitros 750 RC and 950 analyzer. The coefficients of variation were 4.2% at a creatinine concentration of 103 mol/l and 1.92% at 16 mol/l. Estimated GFR (eGFR) (in milliliters per min per 1.73 meters squared) was cal- culated by the Cockcroft-Gault formula, corrected for BSA (2), and the MDRD for- mula (3), both of which are shown below: Cockcroft-Gault formula: [140 age (years)] weight (kg) k c serum creatinine (mol/l) (eq. 1) where k is 1.23 for men and 1.04 for fe- males and c adjusts for BSA. c 1.73/BSA with BSA calculated using the DuBois for- mula (8): BSA (m 2 ) [weight (kg)] 0.425 [height (cm)] 0.725 0.007184 (eq. 2) MDRD formula: 186 [serum creatinine (mol/l)/88.4] 1.154 [age (years)] 0.203 (0.742 if female) (1.210 if African American) (eq. 3) Statistical analysis To compare formula performance over different body weight ranges while main- taining group sizes suitable to make the calculations, subjects were grouped into tertiles according to body weight. Other comparisons were made using the full ranges of the relevant data. eGFR results derived by the Cockcroft-Gault and MDRD formulae were compared with iso- topic GFR by means of two-tailed paired and unpaired t tests as appropriate (con- firmed by nonparametric equivalents for abnormal distributions) and 2 test for proportions and linear regression. Statis- tical test assumptions were checked graphically and by use of suitable statis- tics as required. All calculations were per- formed using SPSS (version 12.0.1). Results are presented as mean SD un- less otherwise indicated. P 0.05 was taken to indicate statistical significance. RESULTS — Demographic character- istics of study participants are summa- rized in Table 1. Normoalbuminuric subjects comprised 91% of participants. A positive correlation between GFR and body weight (r 0.194) was found and was also seen across weight groups. Mean fasting plasma glucose and A1C were sim- ilar between groups. Performance of Cockcroft-Gault– and MDRD formulae– derived eGFRs accord- ing to body weight is presented in Table 1. Bias values show that eGFR significantly underestimates isotopic GFR. However, ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● From the 1 Diabetes Research Unit, Llandough Hospital, Penarth, Cardiff, U.K.; the 2 Wrexham Maelor Hospital, Wrexham, North Wales, U.K.; and the 3 School of Computing and Mathematics, University of Western Sydney, Sydney, Australia. Address correspondence and reprint requests to Richard Chudleigh, 20 Llewelyn Goch, Parc Rhydlafar, St. Fagans, Cardiff, U.K. CF5 6HR. E-mail: rachudleigh@hotmail.com. Received for publication 22 May 2007 and accepted in revised form 1 October 2007. Published ahead of print at http://care.diabetesjournals.org on 12 October 2007. DOI: 10.2337/dc07- 1335. Abbreviations: BSA, body surface area; eGFR, estimated glomerular filtration rate; GFR, glomerular filtration rate; MDRD, Modification of Diet in Renal Disease. A table elsewhere in this issue shows conventional and Syste `me International (SI) units and conversion factors for many substances. © 2008 by the American Diabetes Association. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Clinical Care/Education/Nutrition/Psychosocial Research B R I E F R E P O R T DIABETES CARE, VOLUME 31, NUMBER 1, JANUARY 2008 47