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

      Nephrology Dialysis Transplantation

      Gemfibrozil, adverse effects, Clofibric Acid, analogs & derivatives, Creatinine, blood, Fenofibrate, Fibric Acids, Bezafibrate, Humans, Hypolipidemic Agents, Kidney Diseases, chemically induced, Kidney Transplantation, Postoperative Period, Retrospective Studies, Urea

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          Abstract

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

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          Most cited references 5

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          Can reduction in hypertriglyceridaemia slow progression of microalbuminuria in patients with non-insulin-dependent diabetes mellitus?

          The objective of this study was to investigate whether reduction in hypertriglyceridaemia is associated with a slower rate of progression of microalbuminuria in patients with non-insulin-dependent diabetes mellitus (NIDDM). Fifteen normotensive NIDDM patients with hypertriglyceridaemia (> 2.5 mmol L-1) and microalbuminuria were randomly selected to receive either placebo (eight patients) or gemfibrozil 600 mg b.i.d. (seven patients). Progression of microalbuminuria was assessed during a 12-month follow-up period with measurements, consisting of blood tests and triplicate 24-h urine collections, at 1, 3, 6, 9 and 12 months. All but one patient in the treatment group showed a favourable response (> or = 20% reduction) of hypertriglyceridaemia to gemfibrozil. One patient in the placebo group showed a spontaneous reduction in triglyceride levels. Progression of microalbuminuria was lower, although not statistically significantly so, in the treatment group (36%) than in the placebo group (65%). In the group with > or = 20% reduction in triglyceride levels, progression of MA was significantly lower than in the group with stable or increasing triglyceride levels (+1%, range -56% to +49% vs. +97%, range -35% to +202% respectively) (P = 0.03). Continued follow-up data of patients switching from placebo to gemfibrozil after the trial further support the role of serum triglyceride reduction in stabilizing albumin excretion. In conclusion, the results indicate that, in microalbuminuric NIDDM patients, effective treatment of dyslipidaemia could be associated with stabilization of urinary albumin excretion.
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            Treatment of nephrotic hyperlipoproteinemia with gemfibrozil

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              Creatinine rise after fibrate therapy in renal graft recipients

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                Journal
                11096145

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