Renal and cardiovascular effects of selective cyclooxygenase-2 inhibitors

Selective inhibition of cyclooxygenase-2 (COX-2) was proposed as a novel an ti-inflammatory and analgesic treatment with a reduced profile of gastroint estinal side effects compared with conventional nonsteroidal antiinflammato ry drugs (NSAIDs). Although perceived as an inducible enzyme by inflammator y and other stimuli, COX-2 is constitutively expressed in the kidney. In th is review, we focus on renal and cardiovascular (CV) physiological and path ophysiological characteristics of COX-2 and renal and CV aspects of treatme nt with selective COX-2 inhibitors. Both clinical and experimental studies have shown that renal and CV effects of COX-2 inhibitors are similar to tho se of NSAIDs. These effects include sodium, potassium, and water retention and decreases in renal function, as well as mild to modest increases in blo od pressure (BP) and edema. These deleterious effects are amplified in pati ents with volume and/or sodium depletion. The concomitant administration of COX-2 inhibitors may destabilize BP control in hypertensive patients treat ed with antihypertensive agents. In contrast to the normal kidney, which co uld constitute a target for adverse actions of COX-2 inhibitors, recent exp erimental studies showed increased renal COX-2 expression in several models of renal injury, such as the remnant kidney, renovascular hypertension, an d diabetes, and implicated COX-2 in the progression of renal failure. This suggests that COX-2 inhibitors may confer a renoprotective effect in divers e renal disorders. These intriguing formulations must be delineated further in appropriately designed prospective clinical trials. (C) 2001 by the Nat ional Kidney Foundation, Inc.