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World J Exp Med. Nov 20, 2021; 11(5): 55-65
Published online Nov 20, 2021. doi: 10.5493/wjem.v11.i5.55
Emerging role of cell-free DNA in kidney transplantation
Bhavna Chopra, Kalathil K Sureshkumar
Bhavna Chopra, Nephrology and Hypertension, Allegheny General Hospital, Pittsburgh, PA 15212, United States
Kalathil K Sureshkumar, Division of Nephrology, Department of Medicine, Allegheny General Hospital, Allegheny Health Network, Pittsburgh, PA 15212, United State
Author contributions: Chopra B and Sureshkumar KK performed the literature review and manuscript writing.
Conflict-of-interest statement: Bhavna Chopra received grant/research support from CareDx; Kalathil Sureshkumar received grant/research support and honoraria from CareDx.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Kalathil K Sureshkumar, FRCP, MD, Associate Professor, Division of Nephrology, Department of Medicine, Allegheny General Hospital, Allegheny Health Network, 320 East North Avenue, Pittsburgh, PA 15212, United States. kalathil.sureshkumar@ahn.org
Received: April 9, 2021
Peer-review started: April 9, 2021
First decision: May 14, 2021
Revised: June 1, 2021
Accepted: September 1, 2021
Article in press: September 1, 2021
Published online: November 20, 2021
Abstract

Monitoring kidney transplants for rejection conventionally includes serum creatinine, immunosuppressive drug levels, proteinuria, and donor-specific antibody (DSA). Serum creatinine is a late marker of allograft injury, and the predictive ability of DSA regarding risk of rejection is variable. Histological analysis of an allograft biopsy is the standard method for diagnosing rejection but is invasive, inconvenient, and carries risk of complications. There has been a long quest to find a perfect biomarker that noninvasively predicts tissue injury caused by rejection at an early stage, so that diagnosis and treatment could be pursued without delay in order to minimize irreversible damage to the allograft. In this review, we discuss relatively novel research on identifying biomarkers of tissue injury, specifically elaborating on donor-derived cell-free DNA, and its clinical utility.

Keywords: Biomarker, Donor-derived cell-free DNA, Kidney allograft outcomes, Kidney transplant, Allograft biopsy

Core Tip: Donor-derived cell-free DNA (dd-cfDNA) is now available as a noninvasive biomarker to evaluate the risk of rejection in kidney allografts and other organ transplants. The technology utilizes next generation sequencing and does not require donor genotyping. In this review we discuss the current literature on the utility of dd-cfDNA in kidney transplantation, the limitations, and future directions.