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Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications

  • Andrew Whelton
    Correspondence
    Requests for reprints should be addressed to Andrew Whelton, MD, DSc (Hon), FACP, c/o Universal Clinical Research Center Inc, 1737 Beaver Brook Lane, Hunt Valley, Maryland 21030-1603
    Affiliations
    Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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      Abstract

      Although the prevalence of nephrotoxicity in patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs) is relatively low, the extensive use profile of these agents implies that many persons are at risk. At basal states of normal renal function, the role of renal prostaglandin production for maintenance of stable renal hemodynamic function is relatively limited. Nonetheless, in the clinical setting of reduced renal perfusion as seen in various forms of cardio-renal disease, dehydration, and the aging kidney, the adequacy of renal prostaglandin production mediated predominantly by cyclooxygenase-1 (COX-1) and, potentially, by COX-2 enzyme activity becomes of major significance in the activation of compensatory renal hemodynamics. Inhibition of renal prostaglandin production by the use of NSAIDs in these circumstances can potentially lead to the emergence of several distinct syndromes of disturbed renal function. These include fluid and electrolyte disorders, acute renal dysfunction, nephrotic syndrome/interstitial nephritis, and renal papillary necrosis. In addition, by blunting the homeostatic renal effects of prostaglandins, NSAIDs can adversely influence blood pressure control, particularly during the use of angiotensin-converting enzyme (ACE) inhibitors, diuretics, and β blockers. This is a matter of considerable public health concern, in that some 12 million US citizens are concurrently treated with NSAIDs and antihypertensive drugs. Finally, the risk of congestive heart failure is significantly increased when NSAIDs are given to patients receiving diuretic therapy who have cardiovascular risk factors. Physiologic factors, clinical presentations, diagnostic modalities, and clinical management strategies appropriate to these NSAID-induced renal syndromes are described.
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