Renal effects of COX-2-selective inhibitors

Although nonsteroidal anti-inflammatory drugs (NSAIDs) effectively treat a variety of inflammatory diseases, these agents may cause deleterious effect s on kidney function, especially with respect to solute homeostasis and mai ntenance of renal perfusion and glomerular filtration. NSAIDs act by reduci ng prostaglandin biosynthesis through inhibition of cyclooxygenase (COX) wh ich exists as two isoforms (COX-1 and COX-2). NSAID-induced gastrointestina l toxicity is generally believed to occur through blockade of COX-1 activit y, whereas the anti-inflammatory effects of NSAIDs are thought to occur pri marily through inhibition of the inducible isoform, COX-2. However, the sit uation in the kidney may be somewhat different. Recent studies have demonst rated that COX-2 is constitutively expressed in renal tissues of all specie s; this isoform may, therefore, be intimately involved in prostaglandin-dep endent renal homeostatic processes. Drugs that selectively inhibit COX-2 mi ght, therefore, be expected to produce effects on renal function similar to nonselective NSAIDs which inhibit both COX-1 and COX-2, This assertion is borne out by recent clinical studies showing that the COX-2 inhibitors rofe coxib and celecoxib procedure qualitative changes in urinary prostaglandin excretion, glomerular filtration rate, sodium retention, and their conseque nces similar to nonselective NSAIDs. It, therefore, seems unlikely that the se COX-2 inhibitors (and perhaps their successors) will offer renal safety benefits over nonselective NSAID therapies, and, at this juncture, it is re asonable to assume that all NSAIDs, including COX-2-selective inhibitors, s hare a similar risk for adverse renal effects. Copyright (C) 2001 S. Karger AG, Basel.