Renal Effects of Ibuprofen, Piroxicam, and Sulindac in Patients with Asymptomatic Renal Failure

Study Objective: To evaluate the effects of three chemically distinct nonsteroidal anti-inflammatory drugs (NSAIDs) on renal function in patients with asymptomatic, mild but stable chronic renal failure. Design: Prospectively randomized, triple-crossover study with at least 1-month washout between each of three treatment periods. Setting: Inpatient and outpatient clinical research center of a university teaching hospital. Patients: Convenience sample of 12 women with serum creatinine levels between 130 and 270 µmol/L (1.5 and 3.0 mg/dL). Mean glomerular filtration rate ± standard error was 0.36 ± 0.03 mL/s · m2 (37 ± 3 mL/min · 1.73 m2); mean effective renal plasma flow was 1.6 ± 0.18 mL/s · m2 (166 ± 19 mL/min · 1.73 m2). Interventions: Patients received ibuprofen, 800 mg three times daily; piroxicam, 20 mg daily; and sulindac, 200 mg twice daily for 11 days. Treatment was discontinued if serum creatinine rose by 130 µmol/L (1.5 mg/dL) or serum potassium exceeded 6 mmol/L (6 mEq/L). Measurements and Main Results: Three patients met our criteria for stopping ibuprofen by day 8; however, all patients completed piroxicam and sulindac therapy. When the three patients in whom ibuprofen was withdrawn were rechallenged with ibuprofen, 400 mg three times daily, two again developed evidence of acute renal deterioration. All three regimens suppressed renal prostaglandin production. Conclusions: These findings indicate that a brief course of ibuprofen, a compound widely used on a nonprescription basis, may result in acute renal failure in patients with asymptomatic, mild chronic renal failure. Additional studies are needed to assess the risk of piroxicam and sulindac in patients with more pronounced renal impairment and in patients receiving longer courses of therapy, which, according to our data, may result in drug accumulation.