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

N Engl J Med. 1994 Dec 22;331(25):1675-9. doi: 10.1056/NEJM199412223312502.


Background: People who take analgesic drugs frequently may be at increased risk of end-stage renal disease (ESRD), but the extent of this risk remains unclear.

Methods: We studied 716 patients treated for ESRD and 361 control subjects of similar age from Maryland, Virginia, West Virginia, and Washington, D.C. The study participants were interviewed by telephone about their past use of medications containing acetaminophen, aspirin, and other nonsteroidal antiinflammatory drugs (NSAIDs). For each analgesic drug, the average use (in pills per year) and the cumulative intake (in pills) were examined for any association with ESRD.

Results: Heavier acetaminophen use was associated with an increased risk of ESRD in a dose-dependent fashion. When persons who took an average of 0 to 104 pills per year were used for reference, the odds ratio of ESRD was 1.4 (95 percent confidence interval, 0.8 to 2.4) for those who took 105 to 365 pills per year and 2.1 (95 percent confidence interval, 1.1 to 3.7) for those who took 366 or more pills per year, after adjustment for race, sex, age, and intake of other analgesic drugs. When persons who had taken fewer than 1000 pills containing acetaminophen in their lifetime were used for reference, the odds ratio was 2.0 (95 percent confidence interval, 1.3 to 3.2) for those who had taken 1000 to 4999 pills and 2.4 (95 percent confidence interval, 1.2 to 4.8) for those who had taken 5000 or more pills. Approximately 8 to 10 percent of the overall incidence of ESRD was attributable to acetaminophen use. A cumulative dose of 5000 or more pills containing NSAIDs was also associated with an increased odds of ESRD (odds ratio, 8.8), but the use of aspirin was not.

Conclusions: People who often take acetaminophen or NSAIDs have an increased risk of ESRD, but not those who often take aspirin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetaminophen / adverse effects*
  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Aspirin / adverse effects
  • Case-Control Studies
  • Causality
  • Confidence Intervals
  • Drug Utilization / statistics & numerical data
  • Female
  • Humans
  • Kidney Failure, Chronic / chemically induced*
  • Kidney Failure, Chronic / epidemiology
  • Male
  • Middle Aged
  • Odds Ratio
  • Risk Factors


  • Anti-Inflammatory Agents, Non-Steroidal
  • Acetaminophen
  • Aspirin