Evaluation of the incidence and risk factors for development of fenofibrate-associated nephrotoxicity

Background: Fenofibrate-associated nephrotoxicity has been described in two randomized controlled trials and several observational studies. However, little is known regarding its incidence and the population(s) at risk. Objective: This study aims to quantify the incidence and identify potential risk factors for development of nephrotoxicity in patients receiving fenofibrate. Methods: A retrospective, observational study was conducted in the South Texas Veterans Health Care System. Data were collected regarding baseline demographics, concurrent medical conditions, medications, laboratory results, and fenofibrate use. Results: Within 6 months after initiation of fenofibrate in 428 patients, 115 (27%) experienced an increase in serum creatinine of ≥0.3 mg/dL. Any renal disease (P =.001), chronic kidney disease (P =.01), and diabetes (P =.02) were significantly more prevalent in patients with fenofibrate-associated nephrotoxicity. Patients with nephrotoxicity had significantly greater serum creatinine (1.2 [SD 0.3] vs. 1.1 mg/dL [SD 0.3], P =.0002) and lower estimated glomerular filtration rate (72 [SD 20] vs 81 mL/min/1.73m ² [SD 20], P <.0001) at baseline. These patients also had greater use of calcium channel blockers (P =.0003), furosemide (P =.02), and angiotensin-converting enzyme inhibitors (P =.02). The incidence of nephrotoxicity was significantly greater in patients initiated on high-dose versus those on low-dose fenofibrate (P =.002). In a multivariable regression model, renal disease (P =.02), high-dose fenofibrate (P =.001), and dihydropyridine calcium channel blocker use (P =.02) were determined to be independent predictors of development of increased serum creatinine on fenofibrate. Conclusion: This observational study suggests fenofibrate-associated nephrotoxicity occurs more frequently than previously reported, particularly in patients with renal disease and in those receiving high-dose fenofibrate or concomitant calcium channel blockers.