Opinion Review
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Jun 18, 2022; 12(6): 112-119
Published online Jun 18, 2022. doi: 10.5500/wjt.v12.i6.112
Tolerance protocol of living kidney transplant for developing countries through basic strategy of lymphocyte depletion
Sufi M Suhail
Sufi M Suhail, Department of Renal Medicine, Singapore General Hospital, Singapore 169856, Singapore
Sufi M Suhail, Department of Clinical Research, Duke-NUS Graduate Medical School, Singapore 169856, Singapore
Author contributions: Suhail SM has contributed to the opinion and conclusion of this opinion review solely. He based this opinion review based on his recent publication with a view to confer generalizability of the protocol for the greater interest of ESKD patients of developing countries with an intention to attracting relevant transplant organizations there, where the ESKD burden is high and the availability kidney transplant program is low. The planning of contents of the review and the designs of the figures were done by the author based on the existing information in transplant medicine.
Conflict-of-interest statement: This opinion review is done based on our recent publication with a view to confer generalizability of the protocol for the greater interest of ESKD patients of developing countries.
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: Sufi M Suhail, FRCP, MBBS, MRCP, Assistant Professor, Department of Renal Medicine, Singapore General Hospital, Block 6, Level 6, Outram Road, Singapore 169856, Singapore. grmsms@sgh.com.sg
Received: May 17, 2021
Peer-review started: May 17, 2021
First decision: June 17, 2021
Revised: July 28, 2021
Accepted: May 5, 2022
Article in press: May 5, 2022
Published online: June 18, 2022
Processing time: 394 Days and 0.6 Hours

End-stage kidney failure (ESKD) is a global issue where kidney replacement therapy imposes enormous economic burden to people of developing countries, in addition to the severe limitations to the availability of hemodialysis and peritoneal dialysis technique. The best option of kidney transplantation also requires lifelong combination immunosuppressive medicines, the cost of which is equally comparable to lifelong dialysis. A strategy of achieving transplant tolerance that requires minimum immunosuppressive medicines, although in experimental stage, also requires state-of-art technology with costly medicines and interventions. This is evidently beyond the reach of ESKD patients of developing countries. Hence, globally in developing countries, a need for an innovative but cost-effective tolerance protocol is a burning need for a successful transplant program. In brief, transplant tolerance is defined as a state of donor-specific unresponsiveness to the allograft antigens without the need for ongoing pharmacologic immunosuppression or with a minimal need. Current state-of-art techniques involves: (1) A state of hematological chimera, for complete tolerance; (2) Prope or partial tolerance where immune-reactive T-lymphocytes are inhibited using monoclonal antibodies; and (3) Chimeric antigen receptor for T-regulatory (T-reg) cell therapy using genetically engineered T-reg cells targeting specific T-lymphocyte receptors for inducing anergy. From our real-world experience in transplant management in post-transplant lympho-proliferative disorders (PTLD), we noticed frequently a drastic reduction in the need of immunosuppressive medicines following lympho-ablative therapy for PTLD. We recently published a case study on a real-world experience transplant case where we explained a partial or prope tolerance that developed after lymphocyte ablation therapy, following which the allograft was maintained with low dose dual standard immunosuppressive medicines. Based on this publication, we propose here an innovative tolerance protocol for living related low risk kidney transplantation for developing countries, in this opinion review.

Keywords: Renal allograft, B and T lymphocytes depletion, Tolerance protocol, Immunosuppressive medicines, Living renal transplant

Core Tip: In this opinion review that is based on our recent publication, the core tip concentrates on achieving a partial or prope tolerance in renal allograft through sequential B and T lymphocyte depletion in an approved and in-practice strategy, for living related and low risk kidney transplantation. The allograft would require a half dose dual immunosuppressive therapy subsequently.