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

BACKGROUND

Some reports indicate that fibrates can induce renal dysfunction. However, the clinical characteristics of these episodes, and the respective nephrotoxicity of the four main fibrates used-namely, fenofibrate, bezafibrate, ciprofibrate, and gemfibrozil-remain ill defined.

METHODS

To better characterize this side-effect, we first reviewed the charts of 27 patients from our institution who developed an impairment of renal function during fibrate therapy. We next analysed the articles (n=24) that contained data on renal function in patients taking fibrates (n=2676).

RESULTS

Among our 27 patients, 25 were on fenofibrate therapy, one was taking bezafibrate, and one ciprofibrate. Nineteen were recipients of solid-organ transplants (kidney recipients, n=15; heart or heart-lung recipients, n=4), and eight were non-transplanted patients with some impairment of renal 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 patients. Renal function returned to baseline in 18/24 patients after fibrate discontinuation. 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 increase of mean creatinine values during therapy was described in all papers on fenofibrate (n=7) and bezafibrate (n=8) (range 8-18% and 8-40% respectively), and in three of four papers dealing with ciprofibrate (range 6-16%). No significant renal impairment was described in any of the eight articles reporting data on gemfibrozil therapy.

CONCLUSION

Therapy with fenofibrate, bezafibrate, and ciprofibrate may induce renal dysfunction. Gemfibrozil appears to be devoid of this side-effect.