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/1.73 m² [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.