Cyclooxygenase‐2 Inhibitor—Associated Acute Renal Failure: Case Report with Rofecoxib and Review of the Literature

Abstract

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.

Effects of celecoxib in young rats: Histopathological changes in tissues and alterations of oxidative stress/antioxidant defense system

“…COX-2 inhibition by selective inhibitors has been shown to disrupt renal physiology by decreasing renal blood flow and glomerular filtration rate in clinical studies on healthy subjects (Papaioannides et al, 2001). Therefore, hyaline casts observed in renal medulla may be secondary to functional changes mediated by the inhibition of renal cyclooxygenases in our study (Morales and Mucksavage, 2002). This finding, in association with increased serum urea levels, may be an early indicator of renal damage.…”

Cycloxygenase-2 Is Expressed in Vasculature of Normal and Ischemic Adult Human Kidney and Is Colocalized with Vascular Prostaglandin E2 EP4 Receptors

“…Selective COX-2 antagonists have recently been developed and are in widespread clinical use. In contrast to expectations, COX-2 selective blockers exhibit adverse effects related to kidney and cardiovascular function; they have antinatriuretic properties; they lower GFR and RBF and can lead to acute renal failure; and they aggravate preexisting hypertension and may lead to adverse cardiovascular outcomes (1)(2)(3)(4)(5)(6). Thus, the data indicate important physiologic roles for COX-2 in human cardiovascular and renal homeostasis, but the renal correlates of these clinical observations remain poorly understood.…”

Adverse Effects of COX-2 Inhibitors

“…These agents can be particularly harmful to renal function in patients depending on the vasodilatory actions of PGs in the kidney. PGs are necessary to preserve renal hemodynamics in conditions associated with high adrenergic and renin-angiotensin stimulation, such as heart failure, liver failure, and renal insufficiency [25,27]. Localization studies show that COX-2 is expressed in the adult rat renal cortex in a restricted subpopulation of cells in the cortical thick ascending limb (c/TAL) cells in the region of macula densa (MD) (a group of cells in the wall of the distal renal tubule next to the juxaglomerular cells, that are sensitive to changes in the salt concentration of the filtrate in the tubule) and in the medullary interstitial cells.…”

“…In addition to their homodynamic effects, PGs are necessary to sustain salt and water excretion. For example, PGE 2 inhibits reabsorption of sodium and chloride and antagonizes antidiuretic hormone [1,13,25,27].…”