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World J Nephrol. Mar 6, 2016; 5(2): 152-157
Published online Mar 6, 2016. doi: 10.5527/wjn.v5.i2.152
Proton-pump inhibitor-induced hypomagnesemia: Current research and proposed mechanisms
Jeffrey H William, John Danziger
Jeffrey H William, John Danziger, Division of Nephrology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, United States
Author contributions: Both authors contributed to this manuscript.
Conflict-of-interest statement: The authors have no conflicts of interest to report, commercial, financial, personal, political, intellectual, religious, or otherwise.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jeffrey H William, MD, Division of Nephrology, Beth Israel Deaconess Medical Center and Harvard Medical School, 171 Pilgrim Road, Libby 2, Boston, MA 02215, United States. jhwillia@bidmc.harvard.edu
Telephone: +1-617-6329880 Fax: +1-617-6329890
Received: October 15, 2015
Peer-review started: October 18, 2015
First decision: November 11, 2015
Revised: December 15, 2015
Accepted: December 29, 2015
Article in press: January 4, 2016
Published online: March 6, 2016
Processing time: 137 Days and 15.8 Hours
Abstract

Since the early reports nearly a decade ago, proton-pump inhibitor-induced hypomagnesemia (PPIH) has become a well-recognized phenomenon. While many observational studies in the inpatient and outpatient populations have confirmed the association of PPI exposure and serum magnesium concentrations, there are no prospective, controlled studies to support causation. Molecular mechanisms of magnesium transporters, including the pH-dependent regulation of transient receptor potential melastatin-6 transporters in the colonic enterocyte, have been proposed to explain the effect of PPIs on magnesium reabsorption, but may be a small part of a more complicated interplay of molecular biology, pharmacology, and genetic predisposition. This review explores the current state of research in the field of PPIH and the proposed mechanisms of this effect.

Keywords: Hypomagnesemia; Proton-pump inhibitor; Magnesium; Nephrology; Renal

Core tip: Proton-pump inhibitor (PPI)-induced hypomagnesemia has become a well-recognized phenomenon over the past decade, through the publications of case reports and larger observational studies in the inpatient and outpatient populations. However, there are no prospective, controlled studies to support causation. Molecular mechanisms of magnesium transporters, including the pH-dependent regulation of transient receptor potential melastatin-6 transporters in the colonic enterocyte, have been proposed to explain the effect of PPIs on magnesium reabsorption, but may only comprise a small part of a more complicated interplay of molecular biology, pharmacology, and genetic predisposition.