Salvadori M, Rosso G. Utility and limitations of the use of donor-derived cell-free DNA in kidney transplantation. World J Transplant 2025; 15(4): 104349 [DOI: 10.5500/wjt.v15.i4.104349]
Corresponding Author of This Article
Maurizio Salvadori, MD, Professor, Department of Renal Transplantation, Careggi University Hospital, Viale Pieraccini 18, Florence 50139, Tuscany, Italy. maurizio.salvadori1@gmail.com
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Transplantation
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Minireviews
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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 19, 2025
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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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Salvadori M, Rosso G. Utility and limitations of the use of donor-derived cell-free DNA in kidney transplantation. World J Transplant 2025; 15(4): 104349 [DOI: 10.5500/wjt.v15.i4.104349]
World J Transplant. Dec 18, 2025; 15(4): 104349 Published online Dec 18, 2025. doi: 10.5500/wjt.v15.i4.104349
Utility and limitations of the use of donor-derived cell-free DNA in kidney transplantation
Maurizio Salvadori, Giuseppina Rosso
Maurizio Salvadori, Department of Renal Transplantation, Careggi University Hospital, Florence 50139, Tuscany, Italy
Giuseppina Rosso, Department of Nephrology, San Giovanni di Dio Hospital, Florence 50143, Toscana, Italy
Co-first authors: Maurizio Salvadori and Giuseppina Rosso.
Author contributions: Salvadori M and Rosso G wrote, revised and approved the manuscript, they contributed equally to this article, they are the co-first authors of this manuscript; and all authors thoroughly reviewed and endorsed the final manuscript.
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: Maurizio Salvadori, MD, Professor, Department of Renal Transplantation, Careggi University Hospital, Viale Pieraccini 18, Florence 50139, Tuscany, Italy. maurizio.salvadori1@gmail.com
Received: December 18, 2024 Revised: March 20, 2025 Accepted: April 8, 2025 Published online: December 18, 2025 Processing time: 336 Days and 15.7 Hours
Abstract
In recent years, the use of new biomarkers in different phases of the diagnosis and treatment of several diseases has allowed substantial improvement in clinical practice. The use of donor-derived cell-free DNA (dd-cfDNA) in organ transplantation has led to significant progress in the treatment of post-transplant outcomes, particularly after kidney transplantation. In addition, the use of dd-cfDNA in organ transplantation has led to significant advancements in post-transplant outcome monitoring. The aim of this study is to review many of the recent studies on the use of this biomarker and to evaluate its most relevant advantages and limitations. dd-cfDNA is released from several types of cells of the transplanted organ, most often from endothelial cells and this happens in the case of organ damage, most often rejection. Its presence in the bloodstream of the recipients is an important sign of graft damage; its principal advantage is in the avoidance of invasive tools such as renal biopsy. Additionally, several studies reported that the finding of dd-cfDNA in the serum may precede histological abnormalities; its utility in the diagnosis of subclinical rejection is extremely important. Among the principal limitations of this tool are the difficulty in distinguishing different forms of graft damage. According to several studies this tool has several limitations in diagnosing T-cell mediated rejection. In addition, particular care should be taken in distinguishing dd-cfDNA from recipient-derived cfDNA.
Core Tip: New biomarkers have allowed to improving our knowledge in clinical medicine, in the field of transplantation in particular. Donor-derived cell-free DNA has proven to be one of the best. Such donor DNA is delivered from the damaged graft into the bloodstream of the recipient. The finding of donor-derived cell-free DNA is a clear sign of damaged graft, more often involving the endothelial cells. Several pathologies may be the cause, most often antibody-mediated rejection. Less frequent, T-cell mediated rejection. Major advantage of such technique is to avoid invasive procedures as renal biopsy.
