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Comment & Response |

Adverse Effects of Proton Pump Inhibitors in Chronic Kidney Disease

Maria Fusaro, MD, PhD1,2; Sandro Giannini, MD2; Maurizio Gallieni, MD3
[+] 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.
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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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June 1, 2016
Roberto Lozano, PhD
1Department of Pharmacy, Hospital Real Ntra Sra de Gracia, Zaragoza, Spain
JAMA Intern Med. 2016;176(6):866-867. doi:10.1001/jamainternmed.2016.1848.
June 1, 2016
Pan Zhao, MD; Zhenman Wei, PhD; Jin Han, PhD
1Clinical Trial Center, Liver Failure Therapy and Research Center, Beijing 302 Hospital (PLA 302 Hospital), Beijing, China2Division of Pharmacology, Beijing 302 Hospital (PLA 302 Hospital), Beijing, China
2Division of Pharmacology, Beijing 302 Hospital (PLA 302 Hospital), Beijing, China
2Division of Pharmacology, Beijing 302 Hospital (PLA 302 Hospital), Beijing, China3Adverse Drug Reaction Monitoring Center, Beijing 302 Hospital (PLA 302 Hospital), Beijing, China
JAMA Intern Med. 2016;176(6):867. doi:10.1001/jamainternmed.2016.1851.
June 1, 2016
Ruben Poesen, MD; Björn Meijers, MD, PhD; Pieter Evenepoel, MD, PhD
1Department of Microbiology and Immunology, Division of Nephrology, University Hospitals Leuven, B-3000 Leuven, Belgium
JAMA Intern Med. 2016;176(6):867-868. doi:10.1001/jamainternmed.2016.1854.
June 1, 2016
Eivind Ness-Jensen, MD, PhD; Reidar Fossmark, MD, PhD
1Department of Gastroenterology and Hepatology, St Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway2Norwegian University of Science and Technology, Trondheim, Norway
JAMA Intern Med. 2016;176(6):868. doi:10.1001/jamainternmed.2016.1857.
June 1, 2016
Francesco Iannuzzella, MD; Mattia Corradini, PhD; Sonia Pasquali, MD
1Nephrology and Dialysis Unit, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy
JAMA Intern Med. 2016;176(6):868-869. doi:10.1001/jamainternmed.2016.1860.
June 1, 2016
Benjamin Lazarus, MBBS; Josef Coresh, MD, PhD; Morgan E. Grams, MD, PhD
1Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland2Division of Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
1Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland3Department of Medicine, Johns Hopkins University, Baltimore, Maryland
JAMA Intern Med. 2016;176(6):869-870. doi:10.1001/jamainternmed.2016.1863.
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