Drug Safety

, Volume 41, Issue 8, pp 817–826 | Cite as

Use of Proton Pump Inhibitors and the Risk of Acute Kidney Injury Among Patients with Rheumatoid Arthritis: Cohort Study

  • Henrik Svanström
  • Marie Lund
  • Mads Melbye
  • Björn Pasternak
Original Research Article



Recent observational studies have indicated that use of proton pump inhibitors may be associated with adverse renal outcomes. The objective of this study was to investigate whether the use of proton pump inhibitors increases the risk of acute kidney injury among patients with rheumatoid arthritis.


We conducted the study as a historical prospective cohort study, including patients with rheumatoid arthritis, 30–84 years of age, during 2004–2015. Among these, we identified and matched episodes of use and non-use of proton pump inhibitors (control episodes) 1:4 on the propensity score, including 24,579 episodes of use of proton pump inhibitors and 98,230 control episodes. The primary outcome was a first diagnosis of acute kidney injury and the secondary outcome was any serious renal event (acute kidney injury or chronic kidney disease). The primary time point for analysis was 120 days after study entry.


The incidence rate of acute kidney injury was 2.2 per 1000 person-years during episodes of use of proton pump inhibitors and 0.9 during control episodes. Use of proton pump inhibitors was associated with a significantly increased risk of acute kidney injury (hazard ratio 2.30, 95% confidence interval 1.26–4.20). The absolute risk difference was 40 (95% confidence interval 8–99) events of acute kidney injury per 100,000 episodes of use of proton pump inhibitors. Use of proton pump inhibitors was also associated with a significantly increased risk of the secondary outcome of any serious renal event (hazard ratio 2.61, 95% confidence interval 1.80–3.80).


This cohort study among patients with rheumatoid arthritis found a significantly increased risk of acute kidney injury associated with the use of proton pump inhibitors. These findings may help inform clinical decision making when considering the risks and benefits of proton pump inhibitor treatment in rheumatoid arthritis.


Compliance with Ethical Standards


The study was supported by Lundbeck Foundation Grant no. R219-2016-270 (Dr. Svanström). Dr. Pasternak was supported by an investigator grant from the Strategic Research Area Epidemiology Program at Karolinska Institutet. The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Conflicts of interest

Henrik Svanström, Mads Melbye, and Björn Pasternak have no conflicts of interest directly relevant to the content of this study. Marie Lund reports personal fees from Dansk Lægemiddel Information A/S, outside the submitted work.

Ethics approval

The study was approved by the Danish Data Protection Agency. Ethics approval is not required for register-based research in Denmark.

Data availability

No additional material or data available.

Supplementary material

40264_2018_663_MOESM1_ESM.pdf (78 kb)
Supplementary material 1 (PDF 77 kb)


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Epidemiology ResearchStatens Serum InstitutCopenhagen SDenmark
  2. 2.Department of Clinical MedicineUniversity of CopenhagenCopenhagenDenmark
  3. 3.Department of MedicineStanford University School of MedicineStanfordUSA
  4. 4.Clinical Epidemiology Unit, Department of Medicine SolnaKarolinska InstitutetStockholmSweden

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