NDT Advance Access originally published online on April 20, 2006
Nephrology Dialysis Transplantation 2006 21(8):2342-2343; doi:10.1093/ndt/gfl177
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Cockroft–Gault or abbreviated-MDRD equations—which ‘weighs’ more in cardiovascular risk?
Email: prodrigo{at}compalencia.orgSir,
Chronic kidney disease (CKD) influences the development and progression of cardiovascular disease. It has been demonstrated that the number of cardiovascular events, global mortality and the rate of hospitalization increase while glomerular filtration rate (GFR) decreases, independently of other cardiovascular risk factors [1]. Also, in accordance with National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) guidelines, it is known that the prevalence of cardiovascular risk factors, such as arterial hypertension and anaemia, increase in every stage of CKD [2]. Obesity is likewise associated with an increased risk of cardiovascular disease and mortality. Data from the Framingham Heart Study show that overweight and obesity account for 23% of the cases of coronary heart disease in men and 15% in women [3]. Due to the high number of patients with CKD and cardiovascular disease in western populations, our aim was to learn the prevalence of obesity and other risk factors in patients attending general practices in two localities. Stages of CKD were defined by abbreviated-Modification of diet in Renal Disease Study (MDRD) or body surface-adjusted Cockroft–Gault (CG) equations, following the recommendations of NKF-DOQI guidelines, although MDRD and CG equations were originally developed to estimate GFR and creatinine clearance, respectively [2].
A total of 1000 patients were studied over a period of 1 year. Serum creatinine was determined by means of a kinetic Jaffé method with sample blank on a Hitachi 917 analyzer (Hitachi, Tokyo, Japan) with reagents from Roche (Roche Diagnostics, Mannheim, Germany). In order to avoid the bias secondary to the lack of a common calibration of the serum creatinine assay across different laboratories, GFR was estimated by equations before and after recalibrating serum creatinine (‘new’ serum creatinine = 1.08 x serum creatinine – 0.215) [4].
We found that the relationships between body mass index (BMI) and GFR were different, depending on the equation used. While CG-estimated GFR was directly related with BMI (R = 0.077, P = 0.016), MDRD-GFR was inversely correlated (R = –0.140, P < 0.001) (Figure 1). Similar results were found after recalibrating creatinine (CG-GFR = 0.070, P = 0.027; MDRD-GFR = –0.110, P = 0.001). The relationships between GFR and BMI were different in males and females. In 367 male patients, CG-GFR was directly related with BMI (R = 0.233, P < 0.001), while MDRD-GFR was not significantly related (R = –0.026, P = 0.627). On the other hand, in 633 female patients, although CG-GFR was not significantly related with BMI (R = 0.010, P = 0.811), MDRD-GFR remained inversely correlated (R = –0.199, P < 0.001).
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BMI means were significantly different in stages 2 and 3 (26.8 ± 4.4 vs 28.1 ± 4.6 kg/m2, P = 0.001) using the MDRD equation, but not with CG-GFR (26.8 ± 4.2 vs 27.0 ± 4.2 kg/m2, P = 0.605). After recalibrating creatinine, BMI means remained significantly different in stages 2 and 3 (27.1 ± 3.9 vs 28.4 ± 5.0 kg/m2, P = 0.020) using the MDRD equation, but not with CG-GFR (27.4 ± 4.0 vs 26.6 ± 4.4 kg/m2, P = 0.064). The percentage of overweight patients was significantly lower in stage 2 with respect to stage 3 (64.0 vs 75.8%, P = 0.007) defined by MDRD, but differences were not significant with CG (65.5 vs 67.0%, P = 0.712). Similarly, the percentage of obese patients was significantly lower in stage 2 than in stage 3 (20.7 vs 32.6%, P = 0.002) defined by MDRD, but differences were not significant with CG (21.4 vs 21.2%, P = 0.955). Percentages of overweight and obese patients were similar after recalibrating creatinine.
Obviously, in the CG formula the presence of weight as a factor influences these findings. Both BMI and CG formulas contain body weight and must be positively related by mathematical coupling. With the CG equation, the greater the weight, the higher was the GFR. Hence, overweight patients seem to have a better GFR. In fact, Saracino et al. [5] have proposed the application of a correction formula for obese subjects, but its use has not been generalized. On the other hand, the abbreviated-MDRD equation does not include weight and is known to over-estimate the GFR of underweight patients [6]. As BMI increases with age and the MDRD equation decreases with age, BMI must be inversely related to MDRD-defined GFR.
Data from the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study showed similar findings. The relationship between BMI and GFR showed completely different directions, depending on the renal function method used [7]. Because of the growing interest in CKD epidemiology and its associated cardiovascular risk factors, the two equations must not be recommended as equivalents in order to know ‘cardio-renal’ relationships. An international effort must be made to reach a GFR-measurement consensus.
Conflict of interest statement. None declared.
1 Health Center ‘Plaza del Ejército’ SACYL Valladolid2 Health Center ‘Pintor Oliva’ SACYL Palencia Spain
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