Fibrate-induced increase in blood urea and creatinine: is gemfibrozil the only innocuous agent?

Background. Some reports indicate that fibrates can induce renal dysfunctio n. However, the clinical characteristics of these episodes, and the respect ive nephrotoxicity of the four main fibrates used-namely, fenofibrate, beza frbrate, ciprofibrate, and gemfibrozil-remain ill defined. Methods. To better characterize this side-effect, we first reviewed the cha rts of 27 patients from our institution who developed an impairment of rena l function during fibrate therapy. We next analysed the articles (n = 24) t hat contained data on renal function in patients taking fibrates (n = 2676) . Results. Among our 27 patients, 25 were on fenofibrate therapy, one was tak ing bezafibrate, and one ciprofibrate. Nineteen were recipients of solid-or gan transplants (kidney recipients, n = 15; heart or heart-lung recipients, n = 4), and eight were non-transplanted patients with some impairment of r enal function. Baseline plasma creatinine ranged from 0.9 to 2.9 mg/dl. It increased by a mean of 40% after the start of fibrate therapy. There was a concomitant increase of blood urea values (mean 36%) in most of the patient s. Renal function returned to baseline in 18/24 patients after fibrate disc ontinuation. However, six patients, all transplant recipients, experienced a permanent increase in plasma creatinine. The incidence of fibrate-induced renal dysfunction among our series of kidney transplant recipients was 60% , as it occurred in 15 of the 25 patients who had ever taken fibrates. An i ncrease of mean creatinine values during therapy was described in all paper s on fenofibrate (n = 7) and bezafibrate (n = 8) (range 8-18% and 8-40% res pectively), and in three of four papers dealing with ciprofibrate (range 6- 16%). No significant renal impairment was described in any of the eight art icles reporting data on gemfibrozil therapy. Conclusion. Therapy with fenofibrate, bezafibrate, and ciprofibrate may ind uce renal dysfunction. Gemfibrozil appears to be devoid of this side-effect .