Non-steroidal anti-inflammatory drug-induced renal failure: a brief review of the role of cyclo-oxygenase isoforms.
Non-steroidal anti-inflammatory drugs are efficacious treatments for rheumatoid arthritis and osteoarthritis. However, an adverse effect of treatment with non-steroidal anti-inflammatory drugs is acute renal failure, particularly in a subset of patients that are in a state of effective volume depletion. The frequency of this side-effect in the general treated population is not known, but is probably less than 1% per year. Non-steroidal anti-inflammatory drugs act by inhibiting the synthesis of prostaglandins, which are important mediators of renal function. In the volume-depleted state prostaglandins may counter the vasoconstriction associated with the activation of the renin-angiotensin system. Cyclooxygenase is the rate-limiting enzyme involved in the synthesis of prostaglandins. Cyclooxygenase exists in two forms: a constitutive form (cyclooxygenase-1) and an inducible form (cyclooxygenase-2), which is associated with inflammation. Non-steroidal anti-inflammatory drugs are non-specific inhibitors of both forms of cyclooxygenase. New data are emerging regarding the role of cyclooxygenase-2 in the control of renal function. In normal rat and dog kidney, cyclooxygenase-2 is sparsely expressed in the macula densa, but expression is upregulated when animals are volume depleted. This review explores the possible role of cyclooxygenase-2 in the maintenance of normal renal function in volume depleted states.
Venturini
C M
CM
G.D. Searle, Monsanto Company, St. Louis, Missouri 63167, USA.
Isakson
P
P
Needleman
P
P
D058186:Acute Kidney Injury / Q000139:chemically induced*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D004285:Dogs; D006801:Humans; D007527:Isoenzymes / Q000502:physiology*; D007668:Kidney / Q000201:enzymology / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology*; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D011451:Prostaglandin-Endoperoxide Synthases