Fenofibrate is a potent hypolipemic agent, widely used in patients with mild to severe renal failure in whom hyperlipoproteinemia is frequent. A moderate reversible increase in creatinine plasma levels has been reported with fenofibrate therapy; however, it is not known whether this increased creatininemia reflects a fenofibrate induced alteration of renal function or if fenofibrate interferes with creatinine tubular handling. We prospectively examined the effect of 2 weeks fenofibrate treatment (200 mg daily) on renal function in thirteen hyperlipidemic patients with normal renal function or mild to moderate renal failure (Creat Cl: 110 to 30 ml/min). This study confirms that fenofibrate therapy significantly increases creatininemia in patients with mild to moderate renal failure (147 +/- 12 versus 170 +/- 15 mmol/l; p = 0.014), but does not alter renal hemodynamic nor glomerular filtration rate as assessed by the stability of PAH (304 +/- 56 versus 311 +/- 49 ml/min; p = NS) and inulin clearances (51.7 +/- 6 versus 52.3 +/- 7 ml/min; p = NS). The increase in creatininemia is neither due to an inhibition of creatinine tubular excretion, since no change in creatinine clearance was observed (69 +/- 8 versus 68 +/- 8 ml/min; p = NS), but appears to be associated to a parallel increase in creatinine daily urinary excretion (13.7 +/- 5 versus 15.4 +/- 4 mmol; p = 0.03). In conclusion, fenofibrate therapy in renal patients does not worsen renal function, nor diminish the reliability of creatinine clearance for its follow-up in spite of a significant rise in creatininemia. The mechanism of the fenofibrate-induced increase in urinary creatinine excretion remains to be determined.