Associations of Fenofibrate Therapy With Incidence and Progression of CKD in Patients With Type 2 Diabetes

Abstract

Introduction: Abnormalities in lipid metabolism may contribute to the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes. Fenofibrate induces early and reversible reduction in estimated glomerular filtration rate (eGFR), but it may have protective effects on microvascular complications of diabetes. We hypothesized that randomization to fenofibrate versus placebo would be associated with beneficial long-term effects on kidney outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants. Methods: We conducted a post hoc analysis in the ACCORD Lipid Trial to examine the association of randomization to fenofibrate versus placebo with change in eGFR and with time-to-development of microalbuminuria, macroalbuminuria, CKD, and kidney failure. Results: We analyzed 2636 participants in the fenofibrate arm and 2632 in the placebo arm. During a median follow-up of 4 years, treatment with fenofibrate was associated with lower rate of eGFR decline (−0.28 ml/min per 1.73 m2 per year in the fenofibrate group vs. −1.25 ml/min per 1.73 m2 per year in the placebo group, P < 0.01) and with lower incidence of microalbuminuria (hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.43–0.72, P < 0.001) and macroalbuminuria (HR 0.72, 95% CI 0.57–0.91, P < 0.001). There was no difference in incidence of CKD (HR 0.92, 95% CI 0.74–1.15, P = 0.46) and/or kidney failure (HR 0.95, 95% CI 0.68–1.33, P = 0.76). Conclusion: Compared with placebo, randomization to fenofibrate was associated with lower rates of incident albuminuria and a slower eGFR decline, but no difference in incidence of CKD or kidney failure in ACCORD participants. Keywords: albuminuria, chronic kidney disease, diabetic nephropathy, fenofibrate, kidney failure