ORIGINAL RESEARCH article
Front. Transplant.
Sec. Abdominal Transplantation
Volume 4 - 2025 | doi: 10.3389/frtra.2025.1624291
Plasma total and donor-derived cell-free DNA predict survival in kidney transplant recipients Length
Provisionally accepted
- 1Department of Medicine, University of Melbourne, Parkville, Australia
- 2Department of Nephrology, Austin Health, Heidelberg, Australia
- 3Australian Centre for Transplantation Excellence and Research, Austin Health, Heidelberg, Australia
- 4Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Parkville, Australia
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Studies evaluating cell-free DNA (cfDNA) in kidney allograft dysfunction have primarily focused on detection of rejection by donor-derived cfDNA (ddcfDNA). The utility of ddcfDNA as a marker of longer-term outcomes has not been examined. This study investigated the prognostic value of plasma total cfDNA, fractional ddcfDNA and absolute ddcfDNA, quantified in 49 adult kidney transplant recipients (KTRs) at the time of indication allograft biopsy between 2014 and 2017. Primary outcomes were death, death-censored graft loss (DCGL), and all graft loss (AGL). During a median follow-up of 6.3 years, 7 patients died, 7 experienced DCGL, and 14 had AGL. Death was predicted by high total cfDNA (>4034 copies/millilitre, hazard ratio (HR) 5.94, 95% CI 1.40-25.13, P=0.008) and low fractional ddcfDNA (<0.67%, HR 10.85, 95% CI 1.32-1408.19, P=0.03), and DCGL was predicted by high fractional ddcfDNA (>0.72%, HR 4.93, 95% CI 1.12-21.72, P=0.04), on univariate analysis. AGL was predicted by high total cfDNA (>4034 copies/millilitre, HR 642, 95% CI 1.15-3.56x105, P=0.045) on multivariate analysis. Absolute ddcfDNA was not associated with survival outcomes. This study demonstrates potential prognostic utility of total cfDNA and fractional ddcfDNA in KTRs with allograft dysfunction. Incorporation of these biomarkers could enhance personalised care, beyond non-invasive detection of rejection.
Keywords: kidney tranplantation, ddcfDNA, Cell-free DNA - cfDNA, prognostic biomarker, Survival
Received: 07 May 2025; Accepted: 15 Aug 2025.
Copyright: © 2025 Graver, Power and Whitlam. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Alison Graver, Department of Medicine, University of Melbourne, Parkville, Australia
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