Proton pump inhibitors and traditional nonsteroidal anti-inflammatory drugs and the risk of acute interstitial nephritis and acute kidney injury

Pharmacoepidemiol Drug Saf. 2012 Nov;21(11):1155-72. doi: 10.1002/pds.3329. Epub 2012 Aug 9.


Purpose: This study aims to examine the associations between proton pump inhibitors (PPIs), traditional nonsteroidal anti-inflammatory drugs (tNSAIDs), PPI + tNSAID co-exposure, and the development of the following: (i) acute interstitial nephritis (AIN), a specific kidney injury often attributed to these drugs, and (ii) acute kidney injury (AKI), a general kidney injury encompassing AIN.

Methods: Two retrospective case-control studies were conducted, one for each outcome, within the General Practice Research Database. Cases were diagnostic-coded AIN (primary outcome) or AKI (secondary outcome) events. Controls were matched on age, sex, and general practitioner practice. Exposures were defined by the presence/absence of the following mutually exclusive therapies on the index date: (i) PPI alone; (ii) tNSAID alone; (iii) PPI + tNSAID; or (iv) neither PPI nor tNSAID (referent).

Results: Sixty-eight AIN cases and 3347 controls were identified. The adjusted odds ratios (ORs) for PPI and tNSAID exposures alone were 3.20 (0.80-12.79) and 1.90 (0.65-5.51), respectively. Numerous sensitivity analyses produced adjusted ORs for AIN between 3.0 and 7.7, and 1.6 and 1.9, respectively. We identified 27,982 AKI cases and 1,323,850 controls. The adjusted ORs for PPI alone, tNSAID alone, and PPI + tNSAID exposures were 1.05 (0.97-1.14), 1.31 (1.25-1.37), and 1.33 (1.07-1.64), respectively. Numerous sensitivity analyses produced adjusted ORs for AKI between 1.0 and 1.1, 1.1 and 1.3, and 1.3 and 1.4, respectively.

Conclusions: Proton pump inhibitor exposure may increase the odds of AIN, but this result was not definitive and should be confirmed in a dataset with more AIN cases to allow for increased statistical precision. tNSAIDs, yet not PPIs, were associated with a significantly increased odds of AKI.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / epidemiology
  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Case-Control Studies
  • Data Interpretation, Statistical
  • Databases, Factual
  • Drug Therapy, Combination
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nephritis, Interstitial / chemically induced*
  • Nephritis, Interstitial / epidemiology
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / adverse effects*
  • Proton Pump Inhibitors / therapeutic use
  • Retrospective Studies
  • Risk
  • United Kingdom / epidemiology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Proton Pump Inhibitors