Renal and cardiovascular effects of selective cyclooxygenase-2 inhibitors

Am J Kidney Dis. 2001 Dec;38(6):1145-57. doi: 10.1053/ajkd.2001.29203.


Selective inhibition of cyclooxygenase-2 (COX-2) was proposed as a novel anti-inflammatory and analgesic treatment with a reduced profile of gastrointestinal side effects compared with conventional nonsteroidal anti-inflammatory drugs (NSAIDs). Although perceived as an inducible enzyme by inflammatory and other stimuli, COX-2 is constitutively expressed in the kidney. In this review, we focus on renal and cardiovascular (CV) physiological and pathophysiological characteristics of COX-2 and renal and CV aspects of treatment with selective COX-2 inhibitors. Both clinical and experimental studies have shown that renal and CV effects of COX-2 inhibitors are similar to those of NSAIDs. These effects include sodium, potassium, and water retention and decreases in renal function, as well as mild to modest increases in blood pressure (BP) and edema. These deleterious effects are amplified in patients with volume and/or sodium depletion. The concomitant administration of COX-2 inhibitors may destabilize BP control in hypertensive patients treated with antihypertensive agents. In contrast to the normal kidney, which could constitute a target for adverse actions of COX-2 inhibitors, recent experimental studies showed increased renal COX-2 expression in several models of renal injury, such as the remnant kidney, renovascular hypertension, and diabetes, and implicated COX-2 in the progression of renal failure. This suggests that COX-2 inhibitors may confer a renoprotective effect in diverse renal disorders. These intriguing formulations must be delineated further in appropriately designed prospective clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Aged
  • Animals
  • Body Water / metabolism
  • Cardiovascular Diseases / chemically induced*
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / adverse effects*
  • Cyclooxygenase Inhibitors / pharmacology
  • Humans
  • Hypertension, Renovascular / metabolism
  • Isoenzymes / antagonists & inhibitors*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney Diseases / chemically induced*
  • Membrane Proteins
  • Prostaglandin-Endoperoxide Synthases
  • Sodium / metabolism


  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Sodium
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases