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

https://doi.org/10.1016/S0002-9343(01)00942-1Get rights and content

Abstract

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.

Section snippets

Sample

Between January 1995 and December 1996, 809 consecutive patients under the age of 76 years were enrolled in four tertiary care centers in southwest Germany before replacement of a hip or knee joint because of advanced osteoarthritis. The study protocol was approved by the ethics committee of the University of Ulm, Germany. After giving written informed consent, participants were interviewed and examined by trained physicians according to a standardized questionnaire and examination procedure.

Results

The mean age of the study participants was over 60 years, and there were more women than men (Table 1). The mean body mass index was high, over 33% of participants had hypercholesterolemia, and more than 50% had hypertension. Regular daily use of any analgesic medication was common, especially NSAIDs. (With the exception of acemethacin, the most commonly used NSAIDs are also common in the United States.) Regular use of aspirin and acetaminophen was less prevalent. A quarter of patients

Discussion

Among patients with advanced osteoarthritis, we observed an only marginally increased prevalence of impaired renal function in regular users of NSAIDs compared with nonusers. Impaired renal function was more common among users of NSAIDs with an intermediate or long half-life (4 hours or longer) and in patients who also used diuretics or ACE inhibitors. The latter risks were mainly the result of the use of diuretics and ACE inhibitors per se, and we found no evidence that NSAIDs exacerbated the

Acknowledgements

We would like to thank the institutions that participated in this study: the Departments of Orthopedic Surgery (head: Dr. W. Puhl) and Trauma Surgery (Dr. L. Kinzl) of the University of Ulm, Hessing Orthopedic Hospital in Augsburg (Dr. Th. Naumann), and Baumann Orthopedic Hospital in Stuttgart (Dr. C.T. Trepte) for their efforts in recruiting the patients; Ms. B. Mack for data processing; and Dr. A. M. Walker for his valuable suggestions.

References (34)

  • M.D Murray et al.

    Acute and chronic effects of nonsteroidal antiinflammatory drugs on glomerular filtration rate in elderly patients

    Am J Med Sci

    (1995)
  • M.D Murray et al.

    Ibuprofen-associated renal impairment in a large general internal medicine practice

    Am J Med Sci

    (1990)
  • M.D Murray et al.

    Renal toxicity of the anti-inflammatory drugs

    Ann Rev Pharmacol Toxicol

    (1993)
  • S.-F Wen

    Nephrotoxicities of nonsteroidal anti-inflammatory drugs

    J Formos Med Assoc

    (1997)
  • U.C Dubach et al.

    An epidemiologic study of abuse of analgesic drugs

    N Engl J Med

    (1991)
  • T.V Perneger et al.

    Risk of kidney failure associated with the use of acetaminophen, aspirin and nonsteroidal antiinflammatory drugs

    N Engl J Med

    (1994)
  • T.S Field et al.

    The renal effects of nonsteroidal anti-inflammatory drugs in older peoplefindings from the established populations for epidemiologic studies of the elderly

    J Am Geriatr Soc

    (1999)
  • D.P Sandler et al.

    Nonsteroidal anti-inflammatory drugs and the risk for chronic renal disease

    Ann Intern Med

    (1991)
  • T Stürmer et al.

    NSAIDs and the kidney

    Curr Opin Nephrol Hypertens

    (2001)
  • S.P Perez Gutthann et al.

    Nonsteroidal anti-inflammatory drugs and the risk of hospitalization for acute renal failure

    Arch Intern Med

    (1996)
  • J.M.M Evans et al.

    Nonsteroidal antiinflammatory drugs and hospitalisation for acute renal failure

    Q J Med

    (1995)
  • S.L Bonney et al.

    Renal safety of two analgesics used over the counteribuprofen and aspirin

    Clin Pharmacol Ther

    (1986)
  • J Unsworth et al.

    Renal impairment associated with nonsteroidal anti-inflammatory drugs

    Ann Rheum Dis

    (1987)
  • R.R Bergamo et al.

    Comparative acute effects of aspirin, diflunisal, ibuprofen and indomethacin on renal function in healthy man

    Am J Nephrol

    (1989)
  • M.E Cook et al.

    Comparative effects of namebutone, sulindac and ibuprofen on renal function

    J Rheumatol

    (1997)
  • A Whelton et al.

    Renal effects of ibuprofen, piroxicam, and sulindac in patients with asymptomatic renal failure. A prospective, randomized, crossover comparison

    Ann Intern Med

    (1993)
  • D Henry et al.

    Consumption of non-steroidal anti-inflammatory drugs and the development of functional renal impairment in elderly subjects. Results of a case-control study

    Br J Clin Pharmacol

    (1997)
  • Cited by (0)

    View full text