Proton Pump Inhibitors, Kidney Damage, and Mortality: An Updated Narrative Review

Adv Ther. 2023 Jun;40(6):2693-2709. doi: 10.1007/s12325-023-02476-3. Epub 2023 May 4.


Since their approval by the Food and Drug Administration (FDA) in 1989, proton pump inhibitors (PPIs) have become one of the most highly utilized drugs in the United States, assuming a position as one of the top 10 most prescribed medications in the country. The purpose of PPIs is to limit the amount of gastric acid secreted by the parietal cells via irreversible inhibition of the H+/K+-ATPase pump, therefore maintaining an elevated gastric acid pH of greater than 4 for 15-21 h. Even though PPIs have many clinical uses, they are not without their adverse effects, mimicking achlorhydria. Besides electrolyte abnormalities and vitamin deficiencies, long-term use of PPIs has been linked to acute interstitial nephritis, bone fractures, poor COVID-19 infection outcomes, pneumonia, and possibly an increase in all-cause mortality. The causality between PPI use and increased mortality and disease risk can be questioned since most studies are observational. Confounding variables can greatly affect an observational study and explain the wide-ranging associations with the use of PPIs. Patients on PPIs are generally older, obese, sicker with a higher number of baseline morbidities, and on more medications than the compared PPI non-users. These findings suggest that PPI users are at a higher risk of mortality and complications based on pre-existing conditions. This narrative review aims to update readers on the concerning effects that proton pump inhibitor use can have on patients and give providers a resource to create informed decisions on appropriate PPI use.

Keywords: AKI; Adverse events; Mortality; PPIs; Proton pump inhibitors.

Publication types

  • Review

MeSH terms

  • COVID-19*
  • Fractures, Bone* / drug therapy
  • Humans
  • Kidney
  • Observational Studies as Topic
  • Proton Pump Inhibitors / adverse effects


  • Proton Pump Inhibitors