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.

[1]  J. O. Davis,et al.  Mechanisms regulating renin release. , 1976, Physiological reviews.

[2]  J. Mcgiff,et al.  Contribution of Prostaglandins to the Renal Circulation in Conscious, Anesthetized, and Laparotomized Dogs , 1977, Circulation research.

[3]  R. Freeman,et al.  Effects of Indomethacin and Meclofenamate on Renin Release and Renal Hemodynamic Function during Chronic Sodium Depletion in Conscious Dogs , 1980, Circulation research.

[4]  K. Seibert,et al.  The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes. , 1990, The Journal of biological chemistry.

[5]  A. Ford-hutchinson,et al.  Expression of mRNA for cyclooxygenase‐1 and cyclooxygenase‐2 in human tissues , 1993, FEBS letters.

[6]  H. Jacobson,et al.  Cyclooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction. , 1994, The Journal of clinical investigation.

[7]  K. Seibert,et al.  Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[8]  A. Whelton Renal Effects of Over‐the‐Counter Analgesics , 1995, Journal of clinical pharmacology.

[9]  J. Gierse,et al.  Expression and selective inhibition of the constitutive and inducible forms of human cyclo-oxygenase. , 1995, The Biochemical journal.

[10]  J. Johnston,et al.  Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase II , 1995, Nature.

[11]  W. Bennett,et al.  The renal effects of nonsteroidal anti-inflammatory drugs: summary and recommendations. , 1996, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[12]  R. S. Rogers,et al.  Synthesis and biological evaluation of the 1,5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benze nesulfonamide (SC-58635, celecoxib). , 1997, Journal of medicinal chemistry.

[13]  P. Kadowitz,et al.  Comparative effects of nabumetone, sulindac, and ibuprofen on renal function. , 1997, The Journal of rheumatology.

[14]  P. Huang,et al.  Cyclooxygenase-2 mediates increased renal renin content induced by low-sodium diet. , 1997, Hypertension.

[15]  R. Holder,et al.  The acute phase and function in early rheumatoid arthritis. C-reactive protein levels correlate with functional outcome. , 1997, The Journal of rheumatology.