Favi E, Morabito M. Obinutuzumab in kidney transplantation: Past, present, and future. World J Transplant 2025; 15(4): 108982 [DOI: 10.5500/wjt.v15.i4.108982]
Corresponding Author of This Article
Evaldo Favi, MD, PhD, Department of General Surgery and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza No. 28, Milan 20122, Lombardy, Italy. evaldofavi@gmail.com
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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/
Dec 18, 2025 (publication date) through Nov 18, 2025
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World Journal of Transplantation
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Favi E, Morabito M. Obinutuzumab in kidney transplantation: Past, present, and future. World J Transplant 2025; 15(4): 108982 [DOI: 10.5500/wjt.v15.i4.108982]
World J Transplant. Dec 18, 2025; 15(4): 108982 Published online Dec 18, 2025. doi: 10.5500/wjt.v15.i4.108982
Obinutuzumab in kidney transplantation: Past, present, and future
Evaldo Favi, Marika Morabito
Evaldo Favi, Marika Morabito, Department of General Surgery and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan 20122, Lombardy, Italy
Evaldo Favi, Department of Clinical Sciences and Community Health, Dipartimento di Eccellenza MUR 2023-2027, Università Degli Studi di Milano, Milan 20122, Lombardy, Italy
Author contributions: Favi E was responsible for drafting the article, critical revision, language revision, and final approval; Morabito M was responsible for drafting the article, reviewing the article, editing the article, and final approval; all the authors read and approved the final version of the manuscript to be published.
Conflict-of-interest statement: The authors do not have any conflicting interests.
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: Evaldo Favi, MD, PhD, Department of General Surgery and Kidney Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via Francesco Sforza No. 28, Milan 20122, Lombardy, Italy. evaldofavi@gmail.com
Received: April 27, 2025 Revised: May 26, 2025 Accepted: August 11, 2025 Published online: December 18, 2025 Processing time: 205 Days and 18.6 Hours
Abstract
Antibody-mediated rejection (ABMR) and recurrent primary renal disease (PRD) represent major causes of kidney transplant (KT) loss. The standard of care for desensitization, ABMR, and relapsing autoimmune glomerulopathies or nephrotic syndrome includes apheresis for antibody removal and polyclonal immunoglobulin for antibody blockage. Although frequently used to achieve B-cell depletion, the administration of the type 1 anti-CD20 monoclonal antibodies (mAb) rituximab (RTX) or ofatumumab (OFA) has failed to demonstrate a significant survival benefit. Obinutuzumab (OBI) is a humanized glycoengineered type 2 anti-CD20 mAb. Compared to RTX or OFA, OBI-induced B-cell depletion is not related to complement-dependent cytotoxicity, mostly operating through antibody-dependent cell-mediated cytotoxicity, antibody-dependent phagocytosis, and direct cell death. These characteristics could play a pivotal role in the development of new anti-rejection strategies, enabling the simultaneous administration of complement inhibitors and B-cell-depleting agents. OBI has also demonstrated more powerful peripheral and central B-cell depletion capacities than RTX, with enhanced effects on memory B cells and plasmablasts. In patients with autoimmune glomerulopathies or multidrug-dependent nephrotic syndrome, OBI has shown encouraging results, representing a potential evolution of the treatment of post-transplant relapsing PRD. The present review summarizes the current knowledge on OBI use in KT setting.
Core Tip: Antibody-mediated rejection and recurrent primary renal diseases remain major causes of kidney transplant loss. Obinutuzumab (OBI) is a type 2 anti-CD20 monoclonal antibody with enhanced peripheral and central B-cell depletion capacities compared to type 1 anti-CD20 monoclonal antibodies. Compared to other B-cell-targeted agents, OBI-induced B-cell depletion is marginally affected by complement function, primarily operating through antibody-dependent cell cytotoxicity, antibody-dependent cell phagocytosis, and direct cell death. These characteristics suggest that OBI might represent a game-changer in the management of highly sensitized transplant candidates, humoral rejection, and relapsing renal diseases. This review summarizes the current knowledge on OBI use in kidney transplantation.
