Khalil MAM, Sadagah NM, Mahmood HHK, Altom AA, Tan J, Al-Qurashi SH. Donor-derived cell-free DNA and its utility in kidney transplantation: A myth or a reality. World J Nephrol 2025; 14(4): 109099 [DOI: 10.5527/wjn.v14.i4.109099]
Corresponding Author of This Article
Muhammad Abdul Mabood Khalil, FRCP, Center of Renal Diseases and Transplantation, King Fahad Armed Forces Hospital Jeddah, Al Kurnaysh Br Road, Al Andalus, Jeddah 23311, Makkah al Mukarramah, Saudi Arabia. doctorkhalil1975@hotmail.com
Research Domain of This Article
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 25, 2025 (publication date) through Dec 23, 2025
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Publication Name
World Journal of Nephrology
ISSN
2220-6124
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA
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Khalil MAM, Sadagah NM, Mahmood HHK, Altom AA, Tan J, Al-Qurashi SH. Donor-derived cell-free DNA and its utility in kidney transplantation: A myth or a reality. World J Nephrol 2025; 14(4): 109099 [DOI: 10.5527/wjn.v14.i4.109099]
World J Nephrol. Dec 25, 2025; 14(4): 109099 Published online Dec 25, 2025. doi: 10.5527/wjn.v14.i4.109099
Donor-derived cell-free DNA and its utility in kidney transplantation: A myth or a reality
Muhammad Abdul Mabood Khalil, Nihal Mohammed Sadagah, Hinda Hassan Khideer Mahmood, Alfatih Abdalla Altom, Jackson Tan, Salem H Al-Qurashi
Muhammad Abdul Mabood Khalil, Nihal Mohammed Sadagah, Hinda Hassan Khideer Mahmood, Alfatih Abdalla Altom, Salem H Al-Qurashi, Center of Renal Diseases and Transplantation, King Fahad Armed Forces Hospital Jeddah, Jeddah 23311, Makkah al Mukarramah, Saudi Arabia
Jackson Tan, Department of Nephrology, RIPAS Hospital Brunei Darussalam, Bander Seri Begawan BA1712, Brunei Darussalam
Author contributions: Khalil MAM, Sadagah NM, Al-Qurashi SH, and Tan J planned and designed the outline of the manuscript; Khalil MAM wrote the manuscript; Sadagah NM, Mahmood HHK, Altom AA, Tan J, and Al-Qurashi SH helped in the literature search and supported in writing; all authors read and agreed to the final manuscript.
Conflict-of-interest statement: The authors declare no conflict of interest in 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: Muhammad Abdul Mabood Khalil, FRCP, Center of Renal Diseases and Transplantation, King Fahad Armed Forces Hospital Jeddah, Al Kurnaysh Br Road, Al Andalus, Jeddah 23311, Makkah al Mukarramah, Saudi Arabia. doctorkhalil1975@hotmail.com
Received: April 29, 2025 Revised: June 9, 2025 Accepted: September 10, 2025 Published online: December 25, 2025 Processing time: 238 Days and 7.5 Hours
Abstract
Renal allograft rejection and its detection are challenging problems for transplant clinicians. Transplant physicians rely on serum creatinine, estimated glomerular filtration rate, proteinuria, donor-specific antibodies, and graft biopsy to detect rejection. The sensitivity and specificity in these blood and urine tests are low, and the invasiveness of graft biopsy has led transplant clinicians to seek alternative diagnostic tools. Cell-free DNA (cfDNA) is a fragment of DNA released from cell death due to necrosis and apoptosis. Donor-derived cfDNA (dd-cfDNA) has been proposed as a potential non-invasive biomarker for detecting rejection. However, one must interpret it cautiously in conditions such as ischemia-reperfusion injury, delayed graft function, BK virus nephropathy, post-kidney biopsy, and dual kidney transplantation, which may cause dd-cfDNA elevation. There is a lack of standardized cutoff values for diagnosing various types of rejections. Low specificity, higher cost, and lack of universal availability are the multiple obstacles to using this tool. There is a need to establish clinical guidelines for its future utility in early rejection detection, graft surveillance, and tailoring of immunosuppression.
Core Tip: Donor-derived cell-free DNA is a biomarker for detecting antibody-mediated rejection. It has a potential role for renal allograft surveillance, assessing the immune system reactivity, and monitoring response to rejection therapy. This minireview will focus on its clinical utilization, method of estimation, quantification, and will provide a way for its integration with clinical parameters and gene profiling for its best utility.
