Cyclooxygenase-2 Inhibitor-Associated Acute Renal Failure: Case Report With Rofecoxib and Review of the Literature

Enid Morales, Pharm.D., Jeffrey J. Mucksavage, Pharm.D.

Disclosures

Pharmacotherapy. 2002;22(10) 

In This Article

Abstract and Introduction

Cyclooxygenase (COX)-2 inhibitors are widely prescribed for their antiinflammatory and analgesic effects. The potential for COX-2 inhibitors to exert deleterious effects on renal function similar to those of traditional nonsteroidal antiinflammatory drugs is not well defined. Until recently, COX-1 was considered responsible for the synthesis of renal prostaglandins. However, COX-2 is also constitutively expressed in the human kidney. Clinical studies have reported a significant decrease in glomerular filtration rate in young and elderly sodium-depleted volunteers given COX-2 inhibitors. We describe the case of a 71-year-old woman who developed acute renal failure after receiving a 50-mg dose of the selective COX-2 inhibitor rofecoxib.

Traditional nonsteroidal antiinflammatory drugs (NSAIDs) inhibit both isoforms of the enzyme cyclooxygenase (COX). The first, COX-1, is constitutively expressed in most cells throughout the body, and its inhibition has been associated with gastrointestinal bleeding and ulceration. In contrast, COX-2 expression is induced in the presence of inflammation and its inhibition results in the therapeutic effects of NSAIDs. Thus, the development of selective COX-2 inhibitors brought about a new way to produce potent antiinflammatory actions with a decreased risk of significant gastrointestinal adverse effects.[1,2,3,4,5,6]

In addition to the gastrointestinal side effects of NSAIDs,[7,8] renal toxicity, including acute renal failure, is described in the literature.[9,10,11] These agents can be particularly harmful to renal function in patients relying on the vasodilatory actions of prostaglandins in the kidney. However, the potential for COX-2 inhibitors to have effects on renal function similar to those of NSAIDs is not well defined, and the role of COX-2 in the human kidney is not fully understood.[12,13,14] Several in vitro[15,16,17,18] and clinical[2,3,4,5,19,20,21,22] studies have begun to elucidate the role of this enzyme and the effects of its inhibition on renal function. Case reports of selective COX-2 inhibitor-associated acute renal failure are emerging.[23,24]

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