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Donor-derived cell-free DNA tracks kidney rejection activity

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Research area:medicine-clinicalclinical-methods

What the study found

The study found that donor-derived cell-free DNA, or dd-cfDNA, reflects activity across the kidney rejection continuum. It was highest in biopsies with microvascular inflammation, including antibody-mediated rejection and mixed rejection, and showed the strongest associations with antibody-mediated rejection/microvascular inflammation and activity indices.

Why the authors say this matters

The authors conclude that dd-cfDNA may serve as a non-invasive readout of graft inflammation. They also suggest that these findings extend the rejection-continuum concept into the non-invasive space.

What the researchers tested

The researchers analyzed 249 indication biopsies from two independent cohorts. They compared dd-cfDNA measured as percentage, absolute copies per milliliter, and a combined continuous model score with histopathology-derived continuous rejection indices.

What worked and what didn't

dd-cfDNA increased with histopathological activity and was highest in biopsies with microvascular inflammation, including antibody-mediated and mixed rejection. T-cell-mediated rejection showed elevated T-cell-mediated rejection/tubulointerstitial inflammation indices but lower and more variable dd-cfDNA, along with increased total cell-free DNA, which the authors say may help explain why low-grade T-cell-mediated rejection is less detectable when dd-cfDNA is expressed only as a percentage.

What to keep in mind

The abstract does not describe clinical outcomes beyond the biopsy associations, and it does not provide limitations in detail. The findings are based on indication biopsies from two cohorts, so the summary is limited to that setting.

Key points

  • dd-cfDNA tracked histopathological activity across the kidney rejection continuum.
  • The strongest dd-cfDNA associations were with antibody-mediated rejection/microvascular inflammation and activity indices.
  • Microvascular inflammation, including antibody-mediated and mixed rejection, showed the highest dd-cfDNA values.
  • T-cell-mediated rejection had elevated tissue-injury indices but lower and more variable dd-cfDNA.
  • The combined continuous model score performed better overall than percentage or absolute dd-cfDNA alone.

Disclosure

Research title:
Donor-derived cell-free DNA tracks kidney rejection activity
Authors:
Lara Benning, Aylin Akifova, Bilgin Osmanodja, Christian Morath, Julia Beck, Ekkehard Schütz, Klemens Budde
Institutions:
Charité – Universitätsmedizin Berlin, Charité – Universitätsmedizin Berlin, Charité – Universitätsmedizin Berlin, Heidelberg University, Heidelberg University, HTG Molecular Diagnostics (United States), Nuremberg Hospital, Paracelsus Medizinische Privatuniversität, University Hospital Heidelberg, University Hospital Heidelberg
Publication date:
2026-02-24
DOI:
10.3389/ti.2026.16099
OpenAlex record:
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AI provenance: This post was generated by gpt-5.4-mini (OpenAI). The original authors did not write or review this post.

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