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
Abstract
BACKGROUND

The adverse renal effects of proton pump inhibitors (PPIs) are increasingly recognized in both the general population and patients with chronic kidney disease. Several pharmacokinetic studies have also raised concerns regarding the interaction between PPIs and immunosuppressive drugs in transplant patients. Whether the adverse effects of PPIs have a clinical significance in kidney transplant recipients remains unclear. We performed this meta-analysis to assess the risk of adverse effects in kidney transplant recipients on PPI compared with those without PPI exposure.

AIM

To investigate the risk of acute rejection, graft loss, hypomagnesemia, renal dysfunction, and overall mortality in kidney transplant recipients on PPI compared with those without PPI exposure.

METHODS

A systematic review was conducted in MEDLINE, EMBASE, and Cochrane databases from inception through October 2018 to identify studies that evaluated the adverse effects of PPIs in kidney transplant recipients, including biopsy-proven acute rejection, graft loss, hypomagnesemia, renal function, and overall mortality. Effect estimates from the individual studies were extracted and combined using random-effect, generic inverse variance method of DerSimonian and Laird. The protocol for this meta-analysis is registered with PROSPERO, No. CRD42018115676.

RESULTS

Fourteen observational studies with 6786 kidney transplant recipients were enrolled. No significant association was found between PPI exposure and the risk of biopsy-proven acute rejection at ≥ 1 year [pooled odds ratio (OR), 1.25; 95% confidence interval (CI), 0.82-1.91, I2 = 55%], graft loss at 1 year (pooled OR = 1.30, 95%CI: 0.75-2.24, I2 = 0%) or 1-year mortality (pooled OR = 1.53, 95%CI: 0.90-2.58, I2 = 34%). However, PPI exposure was significantly associated with hypomagnesemia (pooled OR = 1.56, 95%CI: 1.19-2.05, I2 = 27%). Funnel plots and Egger regression asymmetry test were performed and showed no publication bias.

CONCLUSION

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. Thus, future studies are needed to assess the impact of PPIs on long-term outcomes.

Keywords: Proton pump inhibitors; Kidney; Renal transplantation; Meta-analysis hypomagnesemia; Systematic reviews

Core tip: Several pharmacokinetic studies have raised concerns regarding the interaction between proton pump inhibitors (PPIs) and immunosuppressive drugs in transplant patients. Whether the adverse effects of PPIs have a clinical significance in kidney transplant recipients remains unclear. We performed this meta-analysis to assess the risk of adverse effects in kidney transplant recipients on PPI compared with those without PPI exposure. We demonstrate that PPI use is not associated with significant risks of higher acute rejection, graft loss, or 1-year mortality. However, PPI use is associated with 1.56-fold increased risk of hypomagnesemia. Thus, future studies are needed to assess the impact of PPIs on long-term outcomes.