Proton pump inhibitors are associated with increased risk of development of chronic kidney disease

BMC Nephrol. 2016 Aug 3;17(1):112. doi: 10.1186/s12882-016-0325-4.


Background: Acute interstitial nephritis secondary to proton pump inhibitors (PPIs) frequently goes undiagnosed due to its subacute clinical presentation, which may later present as chronic kidney disease (CKD). We investigated the association of PPI use with the development of CKD and death.

Methods: Two separate retrospective case-control study designs were employed with a prospective logistic regression analysis of data to evaluate the association of development of CKD and death with PPI use. The population included 99,269 patients who were seen in primary care VISN2 clinics from 4/2001 until 4/2008. For evaluation of the CKD outcome, 22,807 with preexisting CKD at the first observation in Veterans Affairs Health Care Upstate New York (VISN2) network data system were excluded. Data obtained included use of PPI (Yes/No), demographics, laboratory data, pre-PPI comorbidity variables.

Results: A total of 19,311/76,462 patients developed CKD. Of those who developed CKD 24.4 % were on PPI. Patients receiving PPI were less likely to have vascular disease, COPD, cancer and diabetes. Of the total of 99,269 patients analyzed for mortality outcome, 11,758 died. A prospective logistic analysis of case-control data showed higher odds for development of CKD (OR 1.10 95 % CI 1.05-1.16) and mortality (OR 1.76, 95 % CI 1.67-1.84) among patients taking PPIs versus those not on PPIs.

Conclusions: Use of proton pump inhibitors is associated with increased risk of development of CKD and death. With the large number of patients being treated with proton pump inhibitors, healthcare providers need to be better educated about the potential side effects of these medications.

Keywords: Chronic kidney disease; Death; Outcomes; Proton pump inhibitors.

MeSH terms

  • Aged
  • Case-Control Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mortality / trends
  • Nephritis, Interstitial / diagnosis
  • Nephritis, Interstitial / etiology
  • Nephritis, Interstitial / mortality
  • Prospective Studies
  • Proton Pump Inhibitors / adverse effects*
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / etiology*
  • Renal Insufficiency, Chronic / mortality*
  • Retrospective Studies
  • Risk Factors


  • Proton Pump Inhibitors