Acute renal failure and interstitial nephritis in a patient treated with rofecoxib: case report and review of the literature.

Abstract

Introduction The clinical efficiency of nonsteroidal antiinflammatory drugs (NSAIDs) has made their use very popular for multiple medical indications. Their adverse effects have been evaluated and are well known. These include fluid and electrolyte abnormalities (1), renal failure (2), gastropathy and gastrointestinal bleeding (3), uncontrolled hypertension (4), and aggravation of congestive heart failure (5). Other side effects involving the small bowel and colon, liver, central nervous system, and hematologic system do exist but are less frequent. The principal mechanism of action (and of adverse reactions) of NSAIDs is inhibition of cyclooxygenase (COX or prostaglandin synthase), which impairs the conversion of arachidonic acid to prostaglandins, prostacyclins, and thromboxanes. However, many other mechanisms of action have also been proposed to explain the diversity of their effects (6). Two isoforms of the COX enzymes have been described. COX-1 produces prostaglandins ubiquitously and regulates cellular housekeeping functions, such as gastric cytoprotection, vascular homeostasis, and kidney function. COX-2, the inducible isoform, was previously thought to be expressed only in inflamed tissues. As a result, the selective inhibition of COX-2 has been proposed to be safer than nonselective NSAIDs, maximizing effectiveness and minimizing toxicity. However, because COX-2 has also been localized in noninflamed tissues, including the kidney, it has been suggested that this isoform has a renal homeostatic function (7). Therefore, inhibition of COX-2 might compromise kidney function, just as do nonselective NSAIDs. A review of clinical trials conducted to evaluate the renal effects of COX-2 inhibitors, particularly rofecoxib and celecoxib, evaluated data on their qualitative effects on renal prostaglandins, glomerular filtration rate, sodium excretion, and their clinical effects on equilibration of blood pressure and occurrence of leg edema. The authors concluded that COX-2 inhibitors had the same relative potential as nonselective NSAIDs for adverse renal effects (8). Because of the known fragility of kidney function in the elderly and the high prevalence of osteoarthritis in this population, many clinical trials have evaluated the renal effects of COX-2 inhibitors in the elderly; these trials also concluded they had the same acceptable safety profile as the nonselective NSAIDs (9–12). Renal hemodynamic effects of the COX-2 inhibitors rofecoxib and celecoxib, leading to acute renal failure, have been analyzed and reviewed (13). In contrast, the occurrence of COX-2 inhibitor-induced interstitial nephritis has been described very rarely. Herein we describe a case of acute renal failure due to severe interstitial nephritis in a young woman treated with rofecoxib, a selective COX-2 inhibitor. This report illustrates the potential for similar renal adverse effects in both selective and nonselective COX inhibitors, and emphasizes the possibility of severe adverse renal effects of COX-2 inhibitors by several different mechanisms, even in young healthy individuals.