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Acute Renal Failure Associated with Rofecoxib

TO THE EDITOR: Cyclooxygenase (COX) consists of two isoforms and is the key enzyme in the biosynthesis of the prostaglandins (1). The so-called unspecific nonsteroidal anti-inflammatory drugs nonselectively inhibit both COX isoenzymes, and the adverse effects of these agents on renal function are well known (1). The newly developed selective COX-2 inhibitors are assumed to exhibit fewer, if any, side effects because the activity of COX-1, which is responsible for the physiologic functions of prostaglandins, is not antagonized. A 49-year-old patient who had undergone renal transplantation was admitted because of suspected acute rejection. Transplantation of a cadaver kidney had been performed 9 years ago. The patient exhibited good renal function (serum creatinine concentration, 115 mol/L [1.3 mg/dL]; creatinine clearance, 0.78 mL/s) 4 weeks before admission. He was receiving maintenance immunosuppressive therapy with prednisone and cyclosporine. The patient had degenerative joint disease and received the COX-2 inhibitor rofecoxib (Vioxx, Merck & Co., Inc., West Point, Pennsylvania) from his family physician (50 mg/d for 4 weeks). During rofecoxib treatment, the serum creatinine concentration progressively increased to 354 mol/L (4.0 mg/dL). No laboratory signs of inflammation, eosinophilia, or cyclosporine toxicity were present. There was no proteinuria, and the urinary sediment was normal. Acute renal failure caused by rofecoxib treatment was diagnosed, and the medication was immediately stopped. The serum creatinine concentration recovered to 106 mol/L (1.2 mg/dL) within 3 days. It has been assumed that COX-1 is principally responsible for the production of prostaglandins in the normal kidney (1). Preliminary data on 3595 patients treated with rofecoxib suggest that the drug has no detrimental effects on renal function (2). However, renal function in patients with an allograft represents a labile prostaglandin-dependent state because of a reduced functioning renal mass and cyclosporine (3). Under such conditions, kidney function may depend on the intact function of both COX isoforms (3). This adverse effect of rofecoxib has not been previously described. We believe that patients with renal allografts should not be treated with COX-2 inhibitors until further information on safety becomes available.