Short-Course Systemic and Topical Non-Steroidal Anti-Inflammatory Drugs: Impact on Adverse Renal Events in Older Adults with Co-Morbid Disease

Drugs Aging. 2021 Feb;38(2):147-156. doi: 10.1007/s40266-020-00824-4. Epub 2020 Nov 30.


Background: Prolonged systemic non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with adverse renal outcomes among older adults. However, there is scant data regarding the renal safety of topical and short-course systemic NSAIDs. We aimed to evaluate the risk of acute adverse renal outcomes among older adults prescribed topical and short-term systemic NSAIDs.

Methods: We conducted a retrospective cohort study of all older adults, age 60 years and above, who received prescriptions between July 2015 and December 2017 from the largest tertiary hospital and a major public primary care institution in Singapore. Data from 6 months before until 30 days after the first prescription were retrieved from electronic medical records. The primary outcome was the incidence of acute kidney injury (serum creatinine increased >26.5 µmol/L or >50% from baseline) and/or hyperkalemia within 30 days. A multi-variate analysis taking into account age, sex, co-morbidities, baseline-estimated glomerular filtration rate and serum potassium, NSAID route of administration, and concurrent renin-angiotensin-aldosterone system blocker and diuretic prescription was performed to evaluate factors associated with the primary outcome.

Results: We identified 12,773 older adults with incident prescriptions: 3982 (31.2%) received short-course systemic NSAIDs, 3784 (29.6%) received topical NSAIDs, and 5007 (39.2%) did not receive any NSAID. Both short-course systemic NSAIDs (adjusted odds ratio [OR] 1.59, 95% confidence interval [CI] 1.41-1.80, p < 0.001) and topical NSAIDs (adjusted OR 1.48, 95% CI 1.31-1.67, p < 0.001), compared with the no-NSAID group, were independently associated with the primary outcome. Among older adults with co-morbid conditions and prescribed NSAIDs, topical NSAIDs had a reduced odds of 30-day incident acute kidney injury and/or hyperkalemia in diabetes mellitus (adjusted OR 0.78, 95% CI 0.65-1.06, p = 0.007), chronic kidney disease (adjusted OR 0.74, 95% CI 0.60-0.90, p = 0.003), and cardiovascular disease (adjusted OR 0.54, 95% CI 0.37-0.79, p < 0.001), compared with short-course systemic NSAIDs.

Conclusions: NSAIDs increased the risk of acute adverse renal events. Topical NSAIDs, compared with short-course systemic NSAIDs, were associated with a reduced incidence of acute kidney injury and/or hyperkalemia among older adults with additional risk factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal* / adverse effects
  • Comorbidity
  • Female
  • Humans
  • Kidney
  • Male
  • Middle Aged
  • Pharmaceutical Preparations*
  • Retrospective Studies


  • Anti-Inflammatory Agents, Non-Steroidal
  • Pharmaceutical Preparations