Elahi T, Ahmed S, Mubarak M. Update on diagnostic and therapeutic strategies for antibody-mediated rejection in kidney transplantation. World J Transplant 2026; 16(1): 111524 [DOI: 10.5500/wjt.v16.i1.111524]
Corresponding Author of This Article
Muhammed Mubarak, Department of Histopathology, Sindh Institute of Urology and Transplantation, Chand Bibi Road, Karachi 74200, Sindh, Pakistan. drmubaraksiut@yahoo.com
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Transplantation
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Review
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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/
Mar 18, 2026 (publication date) through Jan 14, 2026
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World Journal of Transplantation
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2220-3230
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Elahi T, Ahmed S, Mubarak M. Update on diagnostic and therapeutic strategies for antibody-mediated rejection in kidney transplantation. World J Transplant 2026; 16(1): 111524 [DOI: 10.5500/wjt.v16.i1.111524]
World J Transplant. Mar 18, 2026; 16(1): 111524 Published online Mar 18, 2026. doi: 10.5500/wjt.v16.i1.111524
Update on diagnostic and therapeutic strategies for antibody-mediated rejection in kidney transplantation
Tabassum Elahi, Saima Ahmed, Muhammed Mubarak
Tabassum Elahi, Saima Ahmed, Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
Muhammed Mubarak, Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
Author contributions: Elahi T and Ahmed S performed the literature search and prepared the initial draft of the manuscript; Mubarak M meticulously revised and refined the manuscript; Elahi T, Ahmed S, and Mubarak M actively participated in the conceptualization and planning of the study; and all authors reviewed and approved the final version.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Muhammed Mubarak, Department of Histopathology, Sindh Institute of Urology and Transplantation, Chand Bibi Road, Karachi 74200, Sindh, Pakistan. drmubaraksiut@yahoo.com
Received: July 2, 2025 Revised: August 23, 2025 Accepted: December 1, 2025 Published online: March 18, 2026 Processing time: 196 Days and 22.5 Hours
Abstract
Antibody-mediated rejection (AMR) remains a leading cause of kidney allograft failure, posing significant clinical and economic challenges. Donor-specific antibodies against human leukocyte antigens or non-human leukocyte antigens are critical risk factors for AMR and graft loss. The diagnostic criteria and classification of AMR have evolved considerably over the past three decades, driven largely by the Banff classification. The latest Banff 2022 classification introduced two additional subcategories of “microvascular inflammation, donor-specific antibody-negative, C4d-negative” and “probable AMR”. Traditionally, graft monitoring has relied on non-specific markers such as serum creatinine and proteinuria, and the invasive biopsies. Noninvasive tools using blood and urine biomarkers, including cellular assays and molecular profiling, are increasingly being investigated. Technologies such as the Molecular Microscope Diagnostic System show promise, with studies reporting 80% sensitivity and 90% specificity in detecting AMR. Treatment of AMR remains inconsistent. Recent advances, including CD38 antibodies, have demonstrated up to 60% efficacy in reversing AMR, while complement inhibition shows potential in severe early cases. Ongoing clinical trials evaluating high-dose intravenous immunoglobulin, efgartigimod, fostamatinib, and other novel therapies aim to expand treatment options. These developments highlight the need for well-designed clinical trials to validate biomarkers and therapies and to improve long-term outcomes for kidney transplant recipients.
Core Tip: Antibody-mediated rejection remains a leading cause of kidney graft dysfunction and failure. While donor-specific antibodies are a key risk factor, not all are pathogenic. Current diagnostic markers lack sensitivity and often miss subclinical changes, with definitive diagnosis still relying on invasive biopsy. The clinical adoption of noninvasive biomarkers continues to face significant hurdles. Despite advances in understanding antibody-mediated rejection biology, no standardized or approved treatment currently exists. Present guidelines are largely based on earlier consensus, although emerging therapies such as CD38 antibodies and complement inhibitors show promise, particularly in early or severe cases.
