Determinants of impaired renal function with use of nonsteroidal anti-inflammatory drugs: the importance of half-life and other medications

Am J Med. 2001 Nov;111(7):521-7. doi: 10.1016/s0002-9343(01)00942-1.


Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with renal function, but little is known about the effects of the half-life of these agents, or the use of other medications, on renal function.

Subjects and methods: Medication use was assessed during a standardized interview in a cross-sectional study of 802 patients undergoing total joint replacement because of osteoarthritis. Preoperative blood samples were used to estimate creatinine clearance using a standard formula that takes age, sex, and weight into account. Impaired renal function was defined as an estimated creatinine clearance less than 60 mL/min (fifteenth percentile). Multivariable logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between NSAID use (alone or in combination with diuretics or angiotensin-converting enzyme [ACE] inhibitors) and impaired renal function.

Results: NSAID use per se was only marginally associated with impaired renal function (OR = 1.4; 95% CI, 0.9 to 2.2). This association was almost exclusively the result of the use of NSAIDs with a half-life of 4 or more hours (OR = 2.6; 95% CI: 1.2 to 5.7). Patients who used diuretics with NSAIDs (OR = 3.7; 95% CI: 1.7 to 8.3) or without NSAIDs (OR = 3.5; 95% CI: 1.6 to 7.6) had a higher risk of impaired renal function than did patients using NSAIDs alone (OR = 1.6) or none of these drugs (reference). A similar but less pronounced pattern was observed for ACE inhibitors.

Conclusion: NSAID-associated impaired renal function seems to be mainly the result of compounds with intermediate-long half-life. We found no evidence that the adverse effects of diuretics and ACE inhibitors on renal function were greater in those who also used NSAIDs.

Publication types

  • Multicenter Study

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Arthroplasty, Replacement, Hip
  • Comorbidity
  • Confounding Factors, Epidemiologic
  • Cross-Sectional Studies
  • Diuretics / pharmacology*
  • Half-Life
  • Humans
  • Kidney / drug effects*
  • Logistic Models
  • Osteoarthritis, Hip / epidemiology
  • Osteoarthritis, Hip / surgery


  • Angiotensin-Converting Enzyme Inhibitors
  • Anti-Inflammatory Agents, Non-Steroidal
  • Diuretics