Cockcroft’s Formula Underestimates Glomerular Filtration Rate in Diabetic Subjects Treated by Lipid-Lowering Drugs

Diabetic subjects are often dyslipemic and have to be treated by fibrates or statins. These drugs must be cautiously used (and sometimes withdrawn) when chronic renal failure is present. Accurate evaluation of glomerular filtration rate (GFR) is thus of crucial importance in diabetic patients to detect early renal impairment. The Cockroft-Gault formula estimates glomerular function as a function of age, body weight, and serum creatinine, and is recommended by the American Diabetes Association (1).

We evaluated the accuracy of Cockroft’s formula (CF) for predicting GFR, by reference to ⁵¹Cr-EDTA clearance, in 48 diabetic subjects without important renal failure (GFR >60 ml/min).

Diabetic subjects were divided into two groups: 22 were not treated by lipid-lowering drugs (TTT−) and 26 were treated (TTT+; 22 with statin, 4 with fibrates). Results of plasma creatinine, isotopic GFR, CF calculated clearance, and the percent underestimation of CF as compared with isotopic GFR were compared by nonparametric tests (Mann-Whitney U for unpaired and Wilcoxon signed rank for paired data). Number of underestimated (<60 ml/min) CF in both groups was compared by the χ² test. Results are expressed as mean ± SD.

The two groups had similar BMI, (TTT− 26.8 ± 3.5 kg/m² vs. TTT+ 28.7 ± 5.3 kg/m²; NS) and HbA_1c (TTT− 9.0 ± 1.7 vs. TTT−+: 9.3 ± 1.2%; NS). Patients who were not treated were younger than treated patients (50.9 ± 15.9 vs. 61.9 ± 11.6 years; P < 0.01). Total, HDL, and LDL cholesterol did not significantly differ in the two groups. Triglycerides remained higher in treated patients (TTT− 1.5 ± 1.3 g/l vs. TTT+ 2.2 ± 1.5 g/l; P < 0.01). The degree of albuminuria was similar in the two groups (TTT− 168.9 ± 187 mg/24 h vs. TTT+ 275.3 ± 552 mg/24 h; NS).

Despite the fact that treated patients were older than the patients who were not treated, isotopic GFR was only slightly lower in this group of patients (TTT+ 98.5 ± 33.9 ml/mn vs. TTT− 102.3 ± 31.5 ml/mn; NS). Plasma creatinine was slightly higher in the treated group (TTT− 88 ± 15 μmol/l vs. TTT+ 95 ± 20 μmol/l; NS). CF underestimated GFR in both nontreated (TTT− 94.3 ± 27 ml/min, P < 0.01 vs. isotopic GFR) and treated subjects (TTT+ 82.3 ± 30.7 ml/min, P < 0.0005 vs. isotopic GFR). However, the percent underestimation by CF was greater in treated (TTT− −6.4 ± 1.7%, TTT+ −15.1 ± 2%; P < 0.05). In the entire population the percent underestimation of GFR by CF was not correlated with age. Number of falsely renal insufficient subjects according to CF (CF <60 ml/min) was higher in treated subjects (TTT− 3 of 22 = 13.6%, TTT+ 8 of 26 = 30.7%; P < 0,05).

CF is known to underestimate GFR at high values (2), but we find this was more pronounced in diabetic subjects treated with lipid-lowering drugs, despite the fact that their isotopic GFR was slightly lower. This underestimation was not associated with age. Indeed, the agreement between the true GFR and the estimated creatinine clearance depends on the former and should be closest when GFR is <100 ml/min (3), as found in the treated group. It does not depend on the age that is already included in CF. This underestimation may be due to the influence of these drugs on muscles (4) and muscular creatinine production, as already reported with fibrates (5). The use of CF may lead physicians to falsely consider one-third of treated diabetic subjects as renal insufficient and consequently erroneously reduce or withdraw lipid-lowering drugs, based on the proportion whose calculated GFR is falsely <60 ml/min. However, treatment of dyslipidemia is of crucial importance in patients with diabetic nephropathy. Indeed, lipid nephrotoxicity has been identified as a factor involved in the progression of renal injury (6).