Thomas L. Schwenk, MD reviewing Lazarus B et al. JAMA Intern Med 2016 Jan 11. Schoenfeld AJ and Grady D. JAMA Intern Med 2016 Jan 11

Polypharmacy is one possible cause of the increasing prevalence of chronic kidney disease (CKD) in the U.S. population. Proton-pump inhibitor (PPI) use is associated with acute renal injury, but PPIs also have other biological effects, including hypomagnesemia, that can lead to excess risk for CKD. In a population-based, prospective cohort study, researchers followed 10,482 adults (mean age, 63; 80% white) with normal renal function (estimated glomerular filtration rate, >60 mL/minute/1.73 m2); at baseline, 322 participants used PPIs and 956 participants used histamine-2 (H2)–receptor antagonists. During the study (median follow-up, 14 years), PPI use increased markedly, to ≈27% of participants.

At study end, the unadjusted incidence of CKD was significantly higher among baseline-PPI users than among baseline nonusers (14.2 vs. 10.7 cases per 1000 person-years); after statistical adjustment, the difference remained significant (hazard ratio, 1.5). CKD risk for baseline H2–antagonist users remained at baseline levels. A similar replication study in 249,000 participants who were followed for a median 6 years yielded similar results.


These results add to increasing concerns about PPI use, including excess risks for Clostridium difficile infections, pneumonia, and fractures. Editorialists recommend monitoring renal function and magnesium levels in patients who are taking PPIs and who are at high risk for CKD; such patients should switch to H2-antagonists when possible and should not use PPIs for vague complaints of heartburn or dyspepsia.


Lazarus B et al. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med 2016 Jan 11; [e­pub]. (

Schoenfeld AJ and Grady D.Adverse effects associated with proton pump inhibitors. JAMA Intern Med 2016 Jan 11; [e­pub]. (