Skip to main content
SpringerLink
Log in

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

  • Original Research Article
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

Introduction

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.

Methods

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.

Results

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).

Conclusions

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Scarpignato C, Gatta L, Zullo A, Blandizzi C, SIF-AIGO-FIMMG Group, Italian Society of Pharmacology, the Italian Association of Hospital Gastroenterologists and the Italian Federation of General Practitioners. Effective and safe proton pump inhibitor therapy in acid-related diseases: a position paper addressing benefits and potential harms of acid suppression. BMC Med. 2016;14(1):179.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. National Institute for Health and Care Excellence. 2009 updated 2015. Rheumatoid arthritis in adults: management [CG79]. https://www.nice.org.uk/guidance/cg79. Accessed 24 Aug 2017.

  3. Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. BMJ. 2008;336(7634):2–3.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Heidelbaugh JJ, Kim AH, Chang R, Walker PC. Overutilization of proton-pump inhibitors: what the clinician needs to know. Ther Adv Gastroenterol. 2012;5(4):219–32.

    Article  Google Scholar 

  5. Schoenfeld AJ, Grady D. Adverse effects associated with proton pump inhibitors. JAMA Intern Med. 2016;176(2):172–4.

    Article  PubMed  Google Scholar 

  6. Lee J, Mark RG, Celi LA, Danziger J. Proton pump inhibitors are not associated with acute kidney injury in critical illness. J Clin Pharmacol. 2016;56(12):1500–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Leonard CE, Freeman CP, Newcomb CW, Reese PP, Herlim M, Bilker WB, et al. Proton pump inhibitors and traditional nonsteroidal anti-inflammatory drugs and the risk of acute interstitial nephritis and acute kidney injury. Pharmacoepidemiol Drug Saf. 2012;21(11):1155–72.

    Article  PubMed  CAS  Google Scholar 

  8. Antoniou T, Macdonald EM, Hollands S, Gomes T, Mamdani MM, Garg AX, et al. Proton pump inhibitors and the risk of acute kidney injury in older patients: a population-based cohort study. CMAJ Open. 2015;3(2):E166–71.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Klatte DCF, Gasparini A, Xu H, de Deco P, Trevisan M, Johansson ALV, et al. Association between proton pump inhibitor use and risk of progression of chronic kidney disease. Gastroenterology. 2017;153(3):702–10.

    Article  PubMed  CAS  Google Scholar 

  10. Lazarus B, Chen Y, Wilson FP, Sang Y, Chang AR, Coresh J, et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med. 2016;176(2):238–46.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Xie Y, Bowe B, Li T, Xian H, Balasubramanian S, Al-Aly Z. Proton pump inhibitors and risk of incident CKD and progression to ESRD. J Am Soc Nephrol. 2016;27(10):3153–63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Hickson LJ, Crowson CS, Gabriel SE, McCarthy JT, Matteson EL. Development of reduced kidney function in rheumatoid arthritis. Am J Kidney Dis. 2014;63(2):206–13.

    Article  PubMed  CAS  Google Scholar 

  13. Karie S, Gandjbakhch F, Janus N, Launay-Vacher V, Rozenberg S, Mai Ba CU, et al. Kidney disease in RA patients: prevalence and implication on RA-related drugs management: the MATRIX study. Rheumatology. 2007;47(3):350–4.

    Article  CAS  Google Scholar 

  14. Wedemeyer RS, Blume H. Pharmacokinetic drug interaction profiles of proton pump inhibitors: an update. Drug Saf. 2014;37(4):201–11.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Moledina DG, Perazella MA. PPIs and kidney disease: from AIN to CKD. J Nephrol. 2016;29(5):611–6.

    Article  PubMed  CAS  Google Scholar 

  16. Schmidt M, Schmidt SAJ, Sandegaard JL, Ehrenstein V, Pedersen L, Sørensen HT. The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol. 2015;7:449–90.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Helweg-Larsen K. The Danish Register of causes of death. Scand J Public Health. 2011;39(7 Suppl.):26–9.

    Article  PubMed  Google Scholar 

  18. Pottegård A, Schmidt SAJ, Wallach-Kildemoes H, Sørensen HT, Hallas J, Schmidt M. Data resource profile: the Danish National Prescription Registry. Int J Epidemiol. 2017;46(3):798-798f.

    PubMed  Google Scholar 

  19. The Danish Health Data Authority. Medstat.dk. http://medstat.dk/en. Accessed 24 Aug 2017.

  20. Schmidt M, Pedersen L, Sørensen HT. The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol. 2014;29(8):541–9.

    Article  PubMed  Google Scholar 

  21. Brookhart MA, Wyss R, Layton JB, Stürmer T. Propensity score methods for confounding control in nonexperimental research. Circ Cardiovasc Qual Outcomes. 2013;6(5):604–11.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Parsons LS. Reducing bias in a propensity score matched-pair sample using greedy matching techniques. In: Proceedings of the 26th Annual SAS Users Group International Conference. California: Long Beach Convention Center; 2001. p. 214–6.

  23. D’Agostino RB, Rubin DB. Estimating and using propensity scores with partially missing data. J Am Stat Assoc. 2000;95(451):749–59.

    Article  Google Scholar 

  24. Naughton CA. Drug-induced nephrotoxicity. Am Fam Physician. 2008;78(6):743–50.

    PubMed  Google Scholar 

  25. Klepser DG, Collier DS, Cochran GL. Proton pump inhibitors and acute kidney injury: a nested case-control study. BMC Nephrol. 2013;14(1):150.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Blank M-L, Parkin L, Paul C, Herbison P. A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int. 2014;86(4):837–44.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Praga M, González E. Acute interstitial nephritis. Kidney Int. 2010;77(11):956–61.

    Article  PubMed  Google Scholar 

  28. Härmark L, Van Der Wiel HE, De Groot MCH, Van Grootheest AC. Proton pump inhibitor-induced acute interstitial nephritis. Br J Clin Pharmacol. 2007;64(6):819–23.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300, Copenhagen S, Denmark

    Henrik Svanström, Marie Lund, Mads Melbye & Björn Pasternak

  2. Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

    Mads Melbye

  3. Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA

    Mads Melbye

  4. Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden

    Björn Pasternak

Authors
  1. Henrik Svanström
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marie Lund
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mads Melbye
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Björn Pasternak
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Henrik Svanström.

Ethics declarations

Funding

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.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PDF 77 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Svanström, H., Lund, M., Melbye, M. et al. Use of Proton Pump Inhibitors and the Risk of Acute Kidney Injury Among Patients with Rheumatoid Arthritis: Cohort Study. Drug Saf 41, 817–826 (2018). https://doi.org/10.1007/s40264-018-0663-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40264-018-0663-1

Search

Navigation