Kidney function during naproxen therapy in patients at risk for renal insufficiency

The effects of naproxen on renal function in 34 patients with minimally elevated serum creatinine (Scr) or subnormal creatinine clearance (Ccr) were evaluated in a parallel-design study. All patients received open-label naproxen 375 mg twice daily for 2 weeks (phase I); patients were then randomly assigned to receive naproxen 750 mg twice daily (n = 26) or to continue naproxen 375 mg twice daily (n = 8) double-blind for an additional 2 weeks (phase II). Renal function was assessed by Scr, Ccr, and BUN measurements at baseline and at the end of each treatment phase. Neither treatment group had a clinically meaningful change in median laboratory values between baseline and the end of phase I, or between baseline and the end of phase II. During the first 2 weeks of treatment with naproxen 375 mg twice daily, there was no change in Scr. At the time of the first Scr measurement following the increase in naproxen dose to 750 mg twice daily, 13 of 26 patients had Scr levels of 1.1 mg/dL or higher, but four days later, only three patients had Scr levels of 1.1 mg/dL or higher, suggesting that a transient increase in Scr may accompany dosage increase. Chronic administration of naproxen 375 mg twice daily in patients at risk for renal insufficiency based on laboratory evidence of renal impairment was not associated with further deterioration in renal function. An increase in dosage to 750 mg twice daily in such patients appeared to be associated with only small, transient changes in laboratory measures of renal function.