NSAIDs: Acute kidney injury (acute renal failure)

INTRODUCTION

Nonsteroidal antiinflammatory drugs (NSAIDs) are a class of medications used for analgesic and anti-inflammatory benefits. NSAIDs can induce several different forms of kidney injury including hemodynamically-mediated acute kidney injury (AKI), electrolyte and acid-base disorders, acute interstitial nephritis (AIN), which may be accompanied by the nephrotic syndrome, and papillary necrosis (table 1).

This topic reviews hemodynamically-mediated AKI. The roles of NSAIDs in acute interstitial nephritis, chronic kidney disease and electrolytes disorders are discussed elsewhere. (See "Clinical manifestations and diagnosis of acute interstitial nephritis" and "Analgesic-related chronic kidney disease" and "NSAIDs: Electrolyte complications".)

The mechanism of action, therapeutic action, and non-renal-related adverse effects of NSAIDs are also discussed elsewhere. (See "NSAIDs: Mechanism of action" and "NSAIDs: Therapeutic use and variability of response in adults" and "Nonselective NSAIDs: Overview of adverse effects" and "Nonselective NSAIDs: Adverse cardiovascular effects".)

EPIDEMIOLOGY

Adverse renal events occur in approximately 1 to 5 percent of all patients using NSAIDs [1]. Because of the large number of patients that take NSAIDs (estimates of more than 70 million prescriptions and 30 billion over the counter doses annually), this translates to upwards of 2.5 million patients experiencing a nephrotoxic event annually [2].

AKI can occur with any class of traditional non-selective NSAID or COX-2 specific NSAIDs [3-8]. As an example, in a nested case-control study that included 121,722 elderly patients, an increased risk of hospitalization within 30 days was associated with initiation of nonselective NSAIDs (other than naproxen), naproxen, rofecoxib, and celecoxib with relative risks (RR) of 2.3, 2.4, 2.3, and 1.5, respectively, compared with unexposed individuals [8].

           

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Jun 2014. | This topic last updated: May 19, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. Whelton A. Nephrotoxicity of nonsteroidal anti-inflammatory drugs: physiologic foundations and clinical implications. Am J Med 1999; 106:13S.
  2. Green GA. Understanding NSAIDs: from aspirin to COX-2. Clin Cornerstone 2001; 3:50.
  3. Haragsim L, Dalal R, Bagga H, Bastani B. Ketorolac-induced acute renal failure and hyperkalemia: report of three cases. Am J Kidney Dis 1994; 24:578.
  4. Oates JA, FitzGerald GA, Branch RA, et al. Clinical implications of prostaglandin and thromboxane A2 formation (1). N Engl J Med 1988; 319:689.
  5. Patrono C, Dunn MJ. The clinical significance of inhibition of renal prostaglandin synthesis. Kidney Int 1987; 32:1.
  6. Perazella MA. COX-2 selective inhibitors: analysis of the renal effects. Expert Opin Drug Saf 2002; 1:53.
  7. Perazella MA, Tray K. Selective cyclooxygenase-2 inhibitors: a pattern of nephrotoxicity similar to traditional nonsteroidal anti-inflammatory drugs. Am J Med 2001; 111:64.
  8. Schneider V, Lévesque LE, Zhang B, et al. Association of selective and conventional nonsteroidal antiinflammatory drugs with acute renal failure: A population-based, nested case-control analysis. Am J Epidemiol 2006; 164:881.
  9. Braden GL, O'Shea MH, Mulhern JG, Germain MJ. Acute renal failure and hyperkalaemia associated with cyclooxygenase-2 inhibitors. Nephrol Dial Transplant 2004; 19:1149.
  10. Dunn MJ. Are COX-2 selective inhibitors nephrotoxic? Am J Kidney Dis 2000; 35:976.
  11. Perazella MA, Eras J. Are selective COX-2 inhibitors nephrotoxic? Am J Kidney Dis 2000; 35:937.
  12. Swan SK, Rudy DW, Lasseter KC, et al. Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet. A randomized, controlled trial. Ann Intern Med 2000; 133:1.
  13. Gooch K, Culleton BF, Manns BJ, et al. NSAID use and progression of chronic kidney disease. Am J Med 2007; 120:280.e1.
  14. Wei L, Macdonald TM, Jennings C, et al. Estimated GFR reporting is associated with decreased nonsteroidal anti-inflammatory drug prescribing and increased renal function. Kidney Int 2013; Mar 13. doi: 10.1038/ki.2013.76. [Epub ahead of print]
  15. Huerta C, Castellsague J, Varas-Lorenzo C, García Rodríguez LA. Nonsteroidal anti-inflammatory drugs and risk of ARF in the general population. Am J Kidney Dis 2005; 45:531.
  16. Lapi F, Azoulay L, Yin H, et al. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury: nested case-control study. BMJ 2013; 346:e8525.
  17. Dubois RN, Abramson SB, Crofford L, et al. Cyclooxygenase in biology and disease. FASEB J 1998; 12:1063.
  18. Bonvalet JP, Pradelles P, Farman N. Segmental synthesis and actions of prostaglandins along the nephron. Am J Physiol 1987; 253:F377.
  19. Chou SY, Dahhan A, Porush JG. Renal actions of endothelin: interaction with prostacyclin. Am J Physiol 1990; 259:F645.
  20. Oliver JA, Pinto J, Sciacca RR, Cannon PJ. Increased renal secretion of norepinephrine and prostaglandin E2 during sodium depletion in the dog. J Clin Invest 1980; 66:748.
  21. Scharschmidt LA, Dunn MJ. Prostaglandin synthesis by rat glomerular mesangial cells in culture. Effects of angiotensin II and arginine vasopressin. J Clin Invest 1983; 71:1756.
  22. Yared A, Kon V, Ichikawa I. Mechanism of preservation of glomerular perfusion and filtration during acute extracellular fluid volume depletion. Importance of intrarenal vasopressin-prostaglandin interaction for protecting kidneys from constrictor action of vasopressin. J Clin Invest 1985; 75:1477.
  23. Clive DM, Stoff JS. Renal syndromes associated with nonsteroidal antiinflammatory drugs. N Engl J Med 1984; 310:563.
  24. Takahashi K, Schreiner GF, Yamashita K, et al. Predominant functional roles for thromboxane A2 and prostaglandin E2 during late nephrotoxic serum glomerulonephritis in the rat. J Clin Invest 1990; 85:1974.
  25. Heyman SN, Brezis M, Epstein FH, et al. Early renal medullary hypoxic injury from radiocontrast and indomethacin. Kidney Int 1991; 40:632.
  26. Perazella MA. Renal vulnerability to drug toxicity. Clin J Am Soc Nephrol 2009; 4:1275.
  27. Weisbord SD, Bruns FJ, Saul MI, Palevsky PM. Provider use of preventive strategies for radiocontrast nephropathy in high-risk patients. Nephron Clin Pract 2004; 96:c56.
  28. Plantinga L, Grubbs V, Sarkar U, et al. Nonsteroidal anti-inflammatory drug use among persons with chronic kidney disease in the United States. Ann Fam Med 2011; 9:423.
  29. Whelton A, Stout RL, Spilman PS, Klassen DK. Renal effects of ibuprofen, piroxicam, and sulindac in patients with asymptomatic renal failure. A prospective, randomized, crossover comparison. Ann Intern Med 1990; 112:568.