Fenofibrate-associated nephrotoxicity: A review of current evidence

Purpose. The literature describing fenofibrate-associated nephrotoxicity was reviewed. Summary. Fenofibrate-associated nephrotoxicity is an underrecognized adverse effect that is being reported with increasing frequency in the medical literature. A MEDLINE search identified articles describing fenofibrate-associated nephrotoxicity. Two retrospective chart reviews reported this adverse reaction in transplant recipients and patients with renal insufficiency. A case series of six patients noted that the adverse reaction also occurred in patients without a predisposition to renal injury. Two small prospective studies have examined fenofibrate-associated nephrotoxicity, with conflicting findings regarding the mechanism. Finally, a large retrospective review and a population-based cohort study found that patients with preexisting renal disease or taking high-dosage fenofibrate have a higher risk of developing fenofibrate-associated nephrotoxicity. Fenofibrate-associated nephrotoxicity was shown to be reversible with both discontinuation and continued use of fenofibrate, though one study found that the elevations in serum creatinine (SCr) levels were permanent in study participants. Some argue that SCr elevations described in these articles were not due to renal toxicity but may be attributed to reversible mechanisms. While several mechanisms may be biologically plausible, none of the theories have been tested in clinical trials. A possible mechanism for the increase in SCr levels may include changes in renal hemodynamics causing volume depletion and the impairment of generation of vasodilatory prostaglandins, leading to renal vasoconstriction. Conclusion. Fenofibrate-associated nephrotoxicity is an underrecognized adverse drug reaction. Several published reports have detailed possible etiologies; however, data detailing the true incidence of fenofibrate-associated nephrotoxicity and its associated risk factors are limited.