Duration and dosing of Proton Pump Inhibitors associated with high incidence of chronic kidney disease in population-based cohort

PLoS One. 2018 Oct 17;13(10):e0204231. doi: 10.1371/journal.pone.0204231. eCollection 2018.


Background: Proton Pump Inhibitors (PPIs) have been associated with chronic kidney disease (CKD). Our objective was to quantify the association between PPI use and incident CKD in a population-based cohort.

Methods and findings: We used a population-based retrospective cohort, including people aged 15 years or over, between January 1, 2005 and December 31, 2012. PPI use was measured in a follow-up session by recording prescriptions. Incident CKD was defined as an estimated glomerular filtration rate < 60 ml/ min/1.73 m2 and/or urinary albumin level to creatinine level ≥ 30 mg/g, in two or more determinations over a period of at least 3 months of the follow-up. Proton Pump Inhibitor use was associated with incident CKD in analysis adjusted for different clinical variables (Hazard Ratio (HR) 1.18; 95% CI 1.04-1.51) in individuals who used PPI in the basal visit (HR 1.37; 95% CI 1.25-1.50) and in those who started to use PPI during the follow-up. High doses of PPI increased the risk of incident CKD (HR 1.92; 95%CI 1.00-6.19) for any type of exposure to PPIs (HR 2.40; 95%CI 1.65-3.46) and for individuals who used high doses throughout the follow-up. This risk of incident CKD increased after three months' exposure to PPIs, (HR1.78; 95% CI 1.39-2.25) between the third and sixth months and (HR 1.30; 95%CI 1.07-1.72) after the sixth month.

Conclusions: PPI use is associated with a higher risk of incident CKD. This association is greater for high doses and becomes apparent after three months' exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Cohort Studies
  • Drug Administration Schedule
  • Drug Dosage Calculations
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / adverse effects*
  • Renal Insufficiency, Chronic / chemically induced*
  • Renal Insufficiency, Chronic / epidemiology*
  • Renal Insufficiency, Chronic / physiopathology
  • Retrospective Studies
  • Young Adult


  • Proton Pump Inhibitors

Grant support

This work was partly funded by the research project PI15/00140 from FIS, ‘Instituto de Salud Carlos III’, ISCIII, Spanish Ministry of Economy and Competitiveness and by the project ‘Grant to improve the scientific productivity of the research groups of the University of Girona 2016-2018’ (MPCUdG2016). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.