Association of proton pump inhibitors and concomitant drugs with risk of acute kidney injury: A nested case-control study

Keiko Ikuta, Shunsaku Nakagawa, Kenji Momo, Atsushi Yonezawa, Kotaro Itohara, Yuki Sato, Satoshi Imai, Takayuki Nakagawa, Kazuo Matsubara

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10 Citations (Scopus)


Objectives This study aimed to assess whether the combined use of proton pump inhibitors (PPIs) with non-steroidal anti-inflammatory drugs (NSAIDs) or antibiotics (penicillins, macrolides, cephalosporins or fluoroquinolones) was associated with an increased risk of acute kidney injury (AKI). Design A nested case-control study. Setting A health insurance claims database constructed by the Japan Medical Data Center. Participants Patients were eligible if they were prescribed a PPI, NSAID and antibiotic at least once between January 2005 and June 2017. The patients who were new PPI users and did not have any history of renal diseases before cohort entry were included (n=219 082). The mean age was 45 and 44% were women. Interventions Current use of PPIs, NSAIDs, or antibiotics. Primary outcome measures Acute kidney injury. Results During a mean follow-up of 2.4 (SD, 1.7) years, 317 cases of AKI were identified (incidence rate of 6.1/10 000 person-years). The current use of PPIs was associated with a higher risk of AKI compared with past PPI use (unadjusted OR, 4.09; 95% CI, 3.09 to 5.44). The unadjusted ORs of AKI for the current use of PPIs with NSAIDs, cephalosporins and fluoroquinolones, compared with the current use of PPIs alone, were 3.92 (95% CI, 2.40 to 6.52), 2.57 (1.43 to 4.62) and 3.08 (1.50 to 6.38), respectively. The effects of concurrent use of PPIs with NSAIDs, cephalosporins or fluoroquinolones remain significant in the adjusted model. The analyses on absolute risk of AKI confirmed the results from the nested case-control study. Conclusions Concomitant use of NSAIDs with PPIs significantly increased the risk for AKI. Moreover, the results suggested that concomitant use of cephalosporins or fluoroquinolones with PPIs was associated with increased risk of incident AKI.

Original languageEnglish
Article numbere041543
JournalBMJ open
Issue number2
Publication statusPublished - 2021 Feb 15
Externally publishedYes


  • acute renal failure
  • clinical pharmacology
  • epidemiology
  • toxicity

ASJC Scopus subject areas

  • General Medicine


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