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Review
. 2024 Aug 12:37:13239.
doi: 10.3389/ti.2024.13239. eCollection 2024.

Perspective for Donor-Derived Cell-Free DNA in Antibody-Mediated Rejection After Kidney Transplantation: Defining Context of Use and Clinical Implications

Aylin Akifova  1 , Klemens Budde  1 , Michael Oellerich  2 , Julia Beck  3 , Kirsten Bornemann-Kolatzki  3 , Ekkehard Schütz  3 , Bilgin Osmanodja  1
Affiliations
Review

Perspective for Donor-Derived Cell-Free DNA in Antibody-Mediated Rejection After Kidney Transplantation: Defining Context of Use and Clinical Implications

Aylin Akifova et al. Transpl Int. .

Abstract

Antibody-mediated rejection (AMR) is a major cause of graft failure limiting long-term graft survival after kidney transplantation. Current diagnostic strategy to detect AMR is suboptimal and requires further improvement. Previously suggested treatment regimens for AMR could not demonstrate efficacy, however novel therapeutic agents are currently under investigation. Donor-derived cell-free DNA (dd-cfDNA) is a novel non-invasive biomarker for allograft injury, that has been mainly studied in the context of rejection. Its short-half-life in circulation and injury-dependent release are its key advantages that contribute to its superior diagnostic accuracy, compared to traditional biomarkers. Moreover, previous studies showed that dd-cfDNA-release is well-linked to histological and molecular features of AMR, and thus able to reflect real-time injury. Further observations suggest that dd-cfDNA can be used as a suitable screening tool for early detection of AMR in patients with donor-specific-anti-HLA-antibodies (DSA), as well as for monitoring AMR activity after anti-rejection treatment. The weight of evidence suggests that the integration of dd-cfDNA in the graft surveillance of patients with AMR, or those suspicious of AMR (e.g., due to the presence of donor-specific anti-HLA-antibodies) has an added value and might have a positive impact on outcomes in this specific cohort.

Keywords: antibody-mediated rejection; donor-derived cell free DNA; donor-specific antibodies (DSA); kidney transplantation; molecular diagnostics.

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Conflict of interest statement

Authors JB, KB-K, and ES were employed by Chronix Biomedical GmbH. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
An overview of different diagnostic modalities showing the relationship between dd-cfDNA and the molecular, clinical and histological progression within the natural course of AMR [–69].
FIGURE 2
FIGURE 2
Current versus donor-derived cell-free DNA-guided diagnostic and therapeutic approach in kidney transplant recipients with donor-specific antibodies.
See this image and copyright information in PMC

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References

    1. Sellarés J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, et al. Understanding the Causes of Kidney Transplant Failure: The Dominant ROLE of Antibody-Mediated Rejection and Nonadherence. Am J Transpl (2012) 12(2):388–99. Epub 2011 Nov 14. 10.1111/j.1600-6143.2011.03840.x - DOI - PubMed
    1. Mayrdorfer M, Liefeldt L, Wu K, Rudolph B, Zhang Q, Friedersdorff F, et al. Exploring the Complexity of Death-Censored Kidney Allograft Failure. J Am Soc Nephrol (2021) 32(6):1513–26. Epub 2021 Apr 21. 10.1681/ASN.2020081215 - DOI - PMC - PubMed
    1. Böhmig GA, Eskandary F, Doberer K, Halloran PF. The Therapeutic Challenge of LATE Antibody-Mediated Kidney Allograft Rejection. Transpl Int (2019) 32(8):775–88. Epub 2019 May 7. 10.1111/tri.13436 - DOI - PMC - PubMed
    1. Naesens M, Roufosse C, Haas M, Lefaucheur C, Mannon RB, Adam BA, et al. The Banff 2022 Kidney Meeting Report: Reappraisal of Microvascular Inflammation and the ROLE of Biopsy-Based Transcript Diagnostics. Am J Transpl (2024) 24(3):338–49. 10.1016/j.ajt.2023.10.016 - DOI - PubMed
    1. Reed EF, Rao P, Zhang Z, Gebel H, Bray RA, Guleria I, et al. Comprehensive Assessment and Standardization of Solid Phase Multiplex-Bead Arrays for the Detection of Antibodies to HLA. Am J Transpl (2013) 13(7):1859–70. Epub 2013 Jun 13. 10.1111/ajt.12287 - DOI - PMC - PubMed

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The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.