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J R Soc Med. 2001 December; 94(12): 657–658.
PMCID: PMC1282321

Nephrotoxicity in the elderly due to co-prescription of ACE inhibitors and NSAIDs

The report by Dr Adhiyaman and others (October 2001 JRSM, pp. 512-514) of renal failure after co-prescription of angiotensin converting enzyme (ACE) inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs), together with findings on renal function in elderly heart failure patients1, should invoke even greater vigilance in the era following the RALES study (which reported survival benefit from co-prescription of spironolactone and ACE inhibitors in heart failure). Already there are reports not only of deterioration in renal function but also of hyperkalaemia complicating co-prescription of ACE inhibitors, spironolactone, and NSAIDs3,4. Spironolactone aggravates the impairment of potassium excretion in renal failure. NSAIDs are liable to impair potassium excretion in their own right, because they can induce hyporeninaemic hypoaldosteronism, which, in turn, impairs renal potassium excretion5. Selective cyclo-oxygenase-2 (COX-2) inhibitors also seem to carry some risk of nephrotoxicity, as judged by anecdotal reports of acute renal failure associated with rofecoxib6 and celecoxib7, so these drugs may differ little in this respect from conventional NSAIDs. Perhaps the time has come for indiscriminate prescription of NSAIDs to be used as an indicator of clinical underperformance.


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2. Pitt B, Zannad F, Remme W, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341: 709-17 [PubMed]
3. Berry C, McMurray JJV. Serious adverse events experienced by patients with chronic heart failure taking spironolactone. Heart 2001;85: e8. [PMC free article] [PubMed]
4. Schepkens H, Vanholder R, Billiouw J-M, Lamiere N. Life-threatening hyperkalemia during combined therapy with angiotensin-converting enzyme inhibitors and spironolactone: an analysis of 25 cases. Am J Med 2001;110: 438-41 [PubMed]
5. Tan SY, Shapiro R, Franco R, et al. Indomethacin-induced prostaglandin inhibition with hyperkalemia: a reversible cause of hyporeninemic hypoaldosteronism. Ann Intern Med 1979;90: 783-5 [PubMed]
6. Wolf G, Porth J, Stahl RAK. Acute renal failure with rofecoxib. Ann Intern Med 2000;133: 394 [PubMed]
7. Parazella MA, Tray K. Selective cyclooxygenase-2 inhibitors: a pattern of nephrotoxicity similar to traditional nonsteroidal anti-inflammatory drugs. Am J Med 2001;111: 64-6 [PubMed]

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