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Nuclear cell-free DNA on the loose: an early warning signal of ischemia–reperfusion injury in kidney transplantation

Strandberg, Gabriel LU ; Trattner Evetovics, Rebecca LU ; Martin, Myriam LU orcid ; Raihle, Carl LU ; Slivca, Oleg LU ; Alam, Shahnawaz ; Segelmark, Mårten LU orcid ; Christensson, Anders LU ; Nilsson, Bo and Paul, Clara LU , et al. (2026) In Frontiers in Immunology 16. p.01-14
Abstract
Introduction: Cell-free DNA is an emerging marker of allograft injury, yet its role in the immediate phase of ischemia–reperfusion injury remains incompletely understood.

Methods: In this prospective cohort of 127 kidney transplant recipients (86 deceased donors, 41 living donors), intraoperative plasma samples were collected systemically pre-implantation and from the allograft vein postreperfusion. Nuclear and mitochondrial cell-free DNA were quantified, alongside subset assessments of neutrophil extracellular trap markers and soluble C5b-9 as a marker of thromboinflammation. An in vitro necrosis model of human proximal tubular cells evaluated the concordance between cell injury and C5b-9 generation.

Results: An... (More)
Introduction: Cell-free DNA is an emerging marker of allograft injury, yet its role in the immediate phase of ischemia–reperfusion injury remains incompletely understood.

Methods: In this prospective cohort of 127 kidney transplant recipients (86 deceased donors, 41 living donors), intraoperative plasma samples were collected systemically pre-implantation and from the allograft vein postreperfusion. Nuclear and mitochondrial cell-free DNA were quantified, alongside subset assessments of neutrophil extracellular trap markers and soluble C5b-9 as a marker of thromboinflammation. An in vitro necrosis model of human proximal tubular cells evaluated the concordance between cell injury and C5b-9 generation.

Results: An immediate and sustained release of nuclear, but not mitochondrial, cell-free DNA was observed post-reperfusion, predominantly in deceased donor kidneys. This release corresponded with cold ischemic time and delayed graft function while showing temporal correlations with soluble C5b-9, indicating that cell-free DNA release parallels thromboinflammatory activation upon reperfusion. In vitro, C5b-9 generation occurred on necrotic, but not viable, tubular cells, supporting the relationship between cell injury and thromboinflammation. Neutrophil extracellular trap markers did not consistently correlate with early cell-free DNA release.

Conclusion: Immediate nuclear cellfree DNA release upon reperfusion reflects intragraft injury linked to downstream thromboinflammatory activation, underscoring the impact of early ischemia–reperfusion injury. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Frontiers in Immunology
volume
16
article number
1704152
pages
01 - 14
publisher
Frontiers Media S. A.
external identifiers
  • pmid:41573572
  • scopus:105027998021
ISSN
1664-3224
DOI
10.3389/fimmu.2025.1704152
language
English
LU publication?
yes
id
6e729974-e2d7-4c29-b77e-4a3a534da3fd
date added to LUP
2026-01-26 13:59:18
date last changed
2026-01-27 04:00:35
@article{6e729974-e2d7-4c29-b77e-4a3a534da3fd,
  abstract     = {{Introduction: Cell-free DNA is an emerging marker of allograft injury, yet its role in the immediate phase of ischemia–reperfusion injury remains incompletely understood.<br/><br/>Methods: In this prospective cohort of 127 kidney transplant recipients (86 deceased donors, 41 living donors), intraoperative plasma samples were collected systemically pre-implantation and from the allograft vein postreperfusion. Nuclear and mitochondrial cell-free DNA were quantified, alongside subset assessments of neutrophil extracellular trap markers and soluble C5b-9 as a marker of thromboinflammation. An in vitro necrosis model of human proximal tubular cells evaluated the concordance between cell injury and C5b-9 generation.<br/><br/>Results: An immediate and sustained release of nuclear, but not mitochondrial, cell-free DNA was observed post-reperfusion, predominantly in deceased donor kidneys. This release corresponded with cold ischemic time and delayed graft function while showing temporal correlations with soluble C5b-9, indicating that cell-free DNA release parallels thromboinflammatory activation upon reperfusion. In vitro, C5b-9 generation occurred on necrotic, but not viable, tubular cells, supporting the relationship between cell injury and thromboinflammation. Neutrophil extracellular trap markers did not consistently correlate with early cell-free DNA release.<br/><br/>Conclusion: Immediate nuclear cellfree DNA release upon reperfusion reflects intragraft injury linked to downstream thromboinflammatory activation, underscoring the impact of early ischemia–reperfusion injury.}},
  author       = {{Strandberg, Gabriel and Trattner Evetovics, Rebecca and Martin, Myriam and Raihle, Carl and Slivca, Oleg and Alam, Shahnawaz and Segelmark, Mårten and Christensson, Anders and Nilsson, Bo and Paul, Clara and Blom, Anna and Biglarnia, Alireza}},
  issn         = {{1664-3224}},
  language     = {{eng}},
  month        = {{01}},
  pages        = {{01--14}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Immunology}},
  title        = {{Nuclear cell-free DNA on the loose: an early warning signal of ischemia–reperfusion injury in kidney transplantation}},
  url          = {{http://dx.doi.org/10.3389/fimmu.2025.1704152}},
  doi          = {{10.3389/fimmu.2025.1704152}},
  volume       = {{16}},
  year         = {{2026}},
}