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World J Transplant. Dec 18, 2023; 13(6): 299-308
Published online Dec 18, 2023. doi: 10.5500/wjt.v13.i6.299
Anti-thymocyte globulin for treatment of T-cell-mediated allograft rejection
Sumit Acharya, Suraj Lama, Durga Anil Kanigicherla
Sumit Acharya, Suraj Lama, Department of Nephrology, Shahid Dharmabhakta National Transplant Center, Bhaktapur 44800, Nepal
Durga Anil Kanigicherla, Department of Renal Medicine, Manchester University NHS Foundation Trust, Manchester M13 9WL, United Kingdom
Author contributions: Acharya S, Lama S, and Kanigicherla DA performed the necessary article search and review, analyzed the paper, and wrote the manuscript; Acharya S made the figures and tables; all the authors have read and approved the final manuscript.
Conflict-of-interest statement: All authors state that there is no conflict of interest to disclose.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Suraj Lama, MBBS, MRes, PhD, Doctor, Department of Nephrology, Shahid Dharmabhakta National Transplant Center, Dudhpati 1, Bhaktapur, Nepal, Bhaktapur 44800, Nepal. suraj_bhaju@yahoo.com
Received: August 20, 2023
Peer-review started: August 20, 2023
First decision: September 29, 2023
Revised: November 1, 2023
Accepted: November 17, 2023
Article in press: November 17, 2023
Published online: December 18, 2023
Abstract

Anti-thymocyte globulin (ATG) is a pivotal immunosuppressive therapy utilized in the management of T-cell-mediated rejection and steroid-resistant rejection among renal transplant recipients. Commercially available as Thymoglobulin (rabbit-derived, Sanofi, United States), ATG-Fresenius S (rabbit-derived), and ATGAM (equine-derived, Pfizer, United States), these formulations share a common mechanism of action centered on their interaction with cell surface markers of immune cells, imparting immunosuppressive effects. Although the prevailing mechanism predominantly involves T-cell depletion via the complement-mediated pathway, alternate mechanisms have been elucidated. Optimal dosing and treatment duration of ATG have exhibited variance across randomised trials and clinical reports, rendering the establishment of standardized guidelines a challenge. The spectrum of risks associated with ATG administration spans from transient adverse effects such as fever, chills, and skin rash in the acute phase to long-term concerns related to immunosuppression, including susceptibility to infections and malignancies. This comprehensive review aims to provide a thorough exploration of the current understanding of ATG, encompassing its mechanism of action, clinical utility in the treatment of acute renal graft rejections, specifically steroid-resistant cases, efficacy in rejection episode reversal, and a synthesis of findings from different eras of maintenance immunosuppression. Additionally, it delves into the adverse effects associated with ATG therapy and its impact on long-term graft function. Furthermore, the review underscores the existing gaps in evidence, particularly in the context of the Banff classification of rejections, and highlights the challenges faced by clinicians when navigating the available literature to strike the optimal balance between the risks and benefits of ATG utilization in renal transplantation.

Keywords: Anti-thymocyte globulin, T-cell-mediated rejection, Steroid-resistant rejection, Biopsy confirmed acute rejection

Core Tip: Anti-thymocyte globulin is a highly efficient induction agent that can prevent acute rejection and delayed graft function. It is widely used for biopsy confirmed acute rejection reversal and steroid-resistant rejection.