Meta-Analysis
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Mar 18, 2021; 11(3): 70-86
Published online Mar 18, 2021. doi: 10.5500/wjt.v11.i3.70
Belatacept in renal transplantation in comparison to tacrolimus and molecular understanding of resistance pattern: Meta-analysis and systematic review
Jayant Kumar, Isabella Reccia, Francesco Virdis, Mauro Podda, Ajay Kumar Sharma, Ahmed Halawa
Jayant Kumar, Isabella Reccia, Department of Cancer and Surgery, Imperial College, London W12 0HS, United Kingdom
Francesco Virdis, Department of Emergency General Surgery, Royal Free Hospital, London NW3 2QG, United Kingdom
Mauro Podda, Department of Surgery, General, Emergency and Robotic Surgical Unit, San Francesco Hospital, Nuoro 08100, Italy
Ajay Kumar Sharma, Department of Transplantation, Royal Liverpool University Hospital, Liverpool L7 8XP, United Kingdom
Ahmed Halawa, Department of Surgery, Sheffield Teaching Hospitals, Sheffield S10 2JF, United Kingdom
Author contributions: Halawa A and Sharma AK designed the idea of study; Reccia I and Kumar J contributed to literature review and data collection; Kumar J, Reccia I, Podda M, Halawa A, and Sharma AK contributed to manuscript writing and critical revision.
Conflict-of-interest statement: None of the contributing authors have any conflict of interest, including specific financial interests or relationships and affiliations relevant to the subject matter or materials discussed in the manuscript.
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 that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: Jayant Kumar, MD, MSc, PhD, Academic Fellow, Attending Doctor, Senior Research Fellow, Department of Cancer and Surgery, Imperial College, DuCane, London W12 0HS, United Kingdom. jkumar@ic.ac.uk
Received: November 23, 2020
Peer-review started: November 23, 2020
First decision: December 21, 2020
Revised: December 23, 2020
Accepted: February 12, 2021
Article in press: February 12, 2021
Published online: March 18, 2021
Processing time: 112 Days and 6.4 Hours
Abstract
BACKGROUND

The T-cell costimulation blocking agent belatacept has been identified as a possible substitute for calcineurin inhibitors, however, no consensus has been established against its use over the standard care agent Tacrolimus.

AIM

To evaluate the effectiveness of belatacept based maintenance immuno-suppressive regimens in comparison to tacrolimus in renal transplantion.

METHODS

We did extensive search of all the available literature comparing the role of belatacept to tacrolimus in renal transplant recipients by searching the PubMed, Embase, Cochrane, Crossref, Scopus, clinical trials registry on October 5, 2020.

RESULTS

The literature search identified four randomized controlled trials (n = 173 participants) comparing belatacept with tacrolimus. There was no significant difference in estimated renal function at 12 mo [mean difference 4.12 mL/min/1.73 m2, confidence interval (CI): -2.18 to 10.42, P = 0.20]. Further, belatacept group was associated with significant increase in biopsy proven acute rejection [relative risk (RR) = 3.27, CI: 0.88 to 12.11, P = 0.08] and worse 12 mo allograft survival (RR = 4.51, CI: 1.23 to 16.58, P = 0.02). However, incidence of new onset diabetes mellitus was lower with belatacept at 12 mo (RR = 0.26, CI: 0.07 to 0.99, P = 0.05).

CONCLUSION

The evidence reviewed in this meta-analysis suggested that belatacept-based maintenance immunosuppression regimens were associated with an increased risk allograft loss in renal transplant recipients with equivalent renal functioning against standard tacrolimus; however, observed significantly reduced new onset diabetes mellitus after transplantation incidence and lower serum low density lipid profile levels in belatacept group. In addition, the adaptation of belatacept in renal transplantation has been forestalled by increased rates of rejection and resistance owing to development of various effector memory T cells through, parallel differentiation and immunological plasticity.

Keywords: Adverse events; Calcineurin inhibitors; Belatacept; Tacrolimus; Graft failure; Kidney transplantation

Core Tip: This meta-analysis suggested that belatacept-based maintenance immunosuppression regimens were associated with an increased risk allograft loss in renal transplant recipients with equivalent renal functioning against standard tacro-limus.