Fibrate treatment can increase serum creatinine levels.

Sir, We read with great interest the recently published article by Broeders et al. with regard to the ®brate-induced increase in blood urea and creatinine w1x. Taking into account these ®ndings, we retrospectively reviewed the charts of patients treated with ®brates, in the lipid clinic of our university hospital. In the study we included patients without any evidence of renal dysfunction, not receiving nephrotoxic agents or drugs that could affect renal function (such as angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, non-steroidal anti-in¯ammatory drugs, aminoglycosides etc), with available serum urea and creatinine levels before and after treatment with ®brates. Interestingly, in accordance to the results of Broeders et al. a signi®cant increase in serum creatinine levels was observed after cipro®brate and feno®brate administration (Table 1). In addition, similar elevations were observed in serum urea levels after the administration of both drugs (by 17% and 8%, respectively). These increases in serum urea and creatinine levels were evident at the patients' ®rst visit (after a mean period of 6 weeks of therapy) and remained unchanged or slightly elevated during a follow-up period of 8 months (3±18 months). However, as shown in Table 1, no signi®cant change in serum creatinine levels was observed after gem®brozil administration. One possible explanation for these diverse effects of ®bric acid derivatives could be the hypothesis that ®brates, such as feno®brate, cipro®brate and beza®brate, impair the generation of vasodilatory prostaglandins, probably because of the activation of peroxisome proliferator-activated receptors (PPARs), which can down-regulate the expression of the inducible COX-2 enzyme w2± 4x. Gem®brozil, in contrast to the other ®brates, fails to bind and activate PPARs, which may account for the absence of nephrotoxicity observed w5x. We conclude that ®brates, possibly with the exception of gem®brozil, can cause a small though signi®cant increase in serum creatinine levels, which should be taken into account, especially in patients with underlying renal disease or in patients also receiving drugs that may affect renal function, such as kidney transplant recipients. HP. Altered hepatic eicosanoid concentrations in rats treated with the peroxisome proliferators cipro®brate and per¯uorodecanoic acid. Induction of cyclooxygenase-2 expression by per-oxisome proliferators and non-tetradecanoylphorbol 12, 13-myristate-type tumor promoters in immortalized mouse liver cells. and hypolipidemic agents identi®ed as ligands of peroxisome proliferators by coactivator-dependent receptor ligand assay. Effect of gem®brozil on serum levels of prostacyclin and precursor fatty acids in hyperlipidemic patients with type 2 diabetes. Table 1. Effect of ®brates on …