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Comment & Response
June 2016

Adverse Effects of Proton Pump Inhibitors in Chronic Kidney Disease

Author Affiliations
  • 1National Research Council (CNR)–Institute of Clinical Physiology (IFC), Pisa, Italy
  • 2Clinica Medica 1, Department of Medicine, University of Padova, Padua, Italy
  • 3Nephrology and Dialysis Unit, ASST Ospedale Santi Paolo e Carlo, Department of Biomedical and Clinical Sciences “Luigi Sacco,” University of Milano, Milan, Italy
JAMA Intern Med. 2016;176(6):866. doi:10.1001/jamainternmed.2016.1845

To the Editor Proton pump inhibitors (PPIs) are extensively used for common gastrointestinal disorders where the inhibition of gastric acid secretion is desirable, such as gastroduodenal ulcer, dyspepsia and gastroesophageal reflux disease. Lazarus et al1 showed an association between PPI use and a higher risk of incident chronic kidney disease (CKD). Furthermore, the authors touched on PPI induced hypomagnesemia as a possible mediator of CKD worsening. We agree with and support this hypothesis, expanding on the possible adverse effects of inappropriately prescribed PPIs in patients with CKD. Proton pump inhibitors interfere with the active transport of magnesium, and clinically significant phenomena are observed in the carriers of heterozygotic mutations of TRPM6/7.2 Proton pump inhibitor-associated hypomagnesemia has been highlighted both in the general population and patients with CKD. We showed that chronic PPI use is associated with increased vascular calcification risk in hemodialysis patients.3 Because magnesium is acting as inhibitor of calcification, it is possible that PPI-induced hypomagnesemia may worsen vascular calcifications in patients with CKD. Magnesium is also deposited in large quantities in bone, being essential for bone health, and chronic PPI treatment may be associated with clinical spine, forearm or wrist, and total fractures, although not hip fractures and with only a marginal effect on 3-year bone mineral density change at the hip.4

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