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

doi:10.2337/diacare.25.11.2106-a

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Letters: Observations
Letter

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

Caroline Perlemoine, MD¹, Vincent Rigalleau, MD, PHD¹, Laurence Baillet, MD¹, Nicole Barthe, MD², Marie-Christine Delmas-Beauvieux, PD³, Catherine Lasseur, MD⁴ and Henri Gin, MD, PHD¹

¹ Haut-Leveque Hospital, Nutrition-Diabetologie, Pessac, France
² Hospital Pellegrin, Médecine Nucléaire, Bordeaux, France
³ Haut-Leveque Hospital, Laboratoire de biochimie, Pessac, France
⁴ Hospital Pellegrin, Néphrologie, Bordeaux, France

Diabetic subjects are often dyslipemic and have to be treatedby 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 These drugs must be cautiously used(and sometimes withdrawn) when chronic renal failure is present.Accurate evaluation of glomerular filtration rate (GFR) is thusof crucial importance in diabetic patients to detect early renalimpairment. The Cockroft-Gault formula estimates glomerularfunction 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) forpredicting GFR, by reference to ⁵¹Cr-EDTA clearance, in 48 diabeticsubjects without important renal failure (GFR >60 ml/min).

Diabetic subjects were divided into two groups: 22 were nottreated 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 underestimationof CF as compared with isotopic GFR were compared by nonparametrictests (Mann-Whitney U for unpaired and Wilcoxon signed rankfor paired data). Number of underestimated (<60 ml/min) CFin both groups was compared by the ${chi}$ ² test. Results are expressedas mean ± SD.

The two groups had similar BMI, (TTT- 26.8 ± 3.5 kg/m²vs. 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 nottreated were younger than treated patients (50.9 ± 15.9vs. 61.9 ± 11.6 years; P < 0.01). Total, HDL, andLDL 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/24h; NS).

Despite the fact that treated patients were older than the patientswho were not treated, isotopic GFR was only slightly lower inthis group of patients (TTT+ 98.5 ± 33.9 ml/mn vs. TTT-102.3 ± 31.5 ml/mn; NS). Plasma creatinine was slightlyhigher in the treated group (TTT- 88 ± 15 µmol/lvs. TTT+ 95 ± 20 µmol/l; NS). CF underestimatedGFR 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 percentunderestimation by CF was greater in treated (TTT- -6.4 ±1.7%, TTT+ -15.1 ± 2%; P < 0.05). In the entire populationthe percent underestimation of GFR by CF was not correlatedwith age. Number of falsely renal insufficient subjects accordingto 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 wefind this was more pronounced in diabetic subjects treated withlipid-lowering drugs, despite the fact that their isotopic GFRwas slightly lower. This underestimation was not associatedwith age. Indeed, the agreement between the true GFR and theestimated creatinine clearance depends on the former and shouldbe closest when GFR is <100 ml/min (3), as found in the treatedgroup. It does not depend on the age that is already includedin CF. This underestimation may be due to the influence of thesedrugs on muscles (4) and muscular creatinine production, asalready reported with fibrates (5). The use of CF may lead physiciansto falsely consider one-third of treated diabetic subjects asrenal insufficient and consequently erroneously reduce or withdrawlipid-lowering drugs, based on the proportion whose calculatedGFR is falsely <60 ml/min. However, treatment of dyslipidemiais of crucial importance in patients with diabetic nephropathy.Indeed, lipid nephrotoxicity has been identified as a factorinvolved in the progression of renal injury (6).

Footnotes

Address correspondence to Caroline Perlemoine, Nutrition-Diabetologia,Service du Pr GIN, Hopital Haut Levesque, 33 600 Pessac, France.E-mail: caroline.perlemoine{at}wanadoo.fr.

References

American Diabetes Association: Standards of medical care for patients with diabetes mellitus (Position Statement). Diabetes Care 24(Suppl. 1):S33–S43, 2001
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Sampson MJ, Drury PL: Accurate estimation of glomerular filtration rate in diabetic nephropathy from age, body weight, and serum creatinine. Diabetes Care 15:609–612, 1992[Abstract]
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Gin H, Rigalleau V, Aparicio M: Lipids, protein intake, and diabetic nephropathy. Diabet Metab 26:45–53, 2000