Meta-Analysis
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Jun 28, 2019; 9(2): 35-47
Published online Jun 28, 2019. doi: 10.5500/wjt.v9.i2.35
Proton pump inhibitors and adverse effects in kidney transplant recipients: A meta-analysis
Boonphiphop Boonpheng, Charat Thongprayoon, Tarun Bathini, Konika Sharma, Michael A Mao, Wisit Cheungpasitporn
Boonphiphop Boonpheng, Department of Internal Medicine, East Tennessee State University, Johnson City, TN37614, United States
Charat Thongprayoon, Michael A Mao, Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, MN55905, United States
Tarun Bathini, Department of Internal Medicine, University of Arizona, Tucson, AZ85721, United States
Konika Sharma, Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY13326, United States
Wisit Cheungpasitporn, Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS39216, United States
Author contributions: Boonpheng B acquisition of data, analysis and interpretation of data, drafting the article, final approval; Thongprayoon C acquisition of data, analysis and interpretation of data, final approval; Bathini T, Sharma K, and Mao MA interpretation of data, revising the article, final approval; Cheungpasitporn W interpretation of data, revising the article, final approval.
Conflict-of-interest statement: The authors deny any conflict of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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/
Corresponding author: Wisit Cheungpasitporn, MD, Assistant Professor, Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS39216, United States. wcheungpasitporn@gmail.com
Telephone: +1-518-2589978 Fax: +1-507-2667891
Received: February 6, 2019
Peer-review started: February 12, 2019
First decision: March 15, 2019
Revised: March 26, 2019
Accepted: May 14, 2019
Article in press: May 14, 2019
Published online: June 28, 2019
Processing time: 142 Days and 11.9 Hours
ARTICLE HIGHLIGHTS
Research background

Adverse renal effects of PPIs are increasingly recognized in clinical practice. Pharmacokinetic studies have also raised concerns regarding the interaction between PPIs and immuno-suppressive drugs in transplant patients. Whether the adverse effects of PPIs have a clinical significance in kidney transplant recipients remains unclear.

Research motivation

Proton pump inhibitors are commonly used after transplantation for prophylaxis against peptic ulcer disease and for treatment of gastro-esophageal reflux disease or dyspepsia. Prolonged exposure to this class of medication has been shown to be associated with kidney dysfunction, as well as other non-renal adverse outcomes, including hypomagnesemia, fracture, or dementia in the general population. The clinical significance of this drug interaction in kidney transplant recipients is unknown. Several studies have shown a possible increased risk of acute rejection with PPI exposure whereas others have not.

Research objectives

We performed this systematic review and meta-analysis to investigate the adverse outcomes in kidney transplant recipients on PPI compared with those without PPI exposure.

Research methods

A systematic review was conducted in MEDLINE, EMBASE, and Cochrane databases from inception to October 2018 to identify studies that evaluated adverse effects of PPIs in kidney transplant recipients. The outcomes of interest include biopsy-proven acute rejection, graft loss, kidney dysfunction, hypomagnesemia, and overall mortality. The protocol for this meta-analysis is registered with PROSPERO, No. CRD42018115676.

Research results

The authors found no significant association between exposure to PPIs and higher risk of acute biopsy-proven rejection, graft loss, or overall mortality, but a significantly 1.56-fold higher risk of hypomagnesemia among those with PPI exposure was noted. No short-term difference in renal function was found between the two groups.

Research conclusions

PPI use was not associated with significant risks of higher acute rejection, graft loss, or 1-year mortality. However, the risk of hypomagnesemia was significantly increased with PPI use. In the long-term, PPI use may also be associated with kidney dysfunction and increased overall mortality.

Research perspectives

This study demonstrated significant hypomagnesemia in kidney transplant recipients who received PPIs. Since hypomagnesemia is associated with new onset diabetes new-onset diabetes after transplantation, future large-scale clinical studies are needed to assess the impact of PPIs on long-term outcomes.