What the study found
Donor-derived cell-free DNA (dd-cfDNA) increased with histopathological activity in kidney transplant biopsies and was highest in biopsies with microvascular inflammation, including antibody-mediated and mixed rejection. The authors report that dd-cfDNA may serve as a non-invasive readout of graft inflammation.
Why the authors say this matters
The study suggests that dd-cfDNA extends the rejection-continuum concept into a non-invasive setting. The findings indicate that it may complement histopathology-derived rejection indices by reflecting activity across the rejection continuum.
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 that integrates both measures, against newly developed histopathology-derived rejection indices.
What worked and what didn't
dd-cfDNA showed the strongest associations with the antibody-mediated rejection/microvascular inflammation and activity indices. The combined model score had the highest overall associations, outperforming absolute and relative dd-cfDNA measures. T-cell-mediated rejection showed elevated T-cell-mediated rejection/tubulointerstitial inflammation indices but lower and more variable dd-cfDNA, with increased total cfDNA, which the authors present as a plausible explanation for reduced detectability when dd-cfDNA is expressed as a percentage alone.
What to keep in mind
The abstract does not describe limitations beyond the observational comparison across biopsy cohorts. The study reports associations, not direct proof that dd-cfDNA can replace biopsy-based histopathology.
Key points
- dd-cfDNA rose with histopathological activity in kidney transplant biopsies.
- The highest dd-cfDNA levels were seen in microvascular inflammation, including antibody-mediated and mixed rejection.
- The combined continuous model score had the strongest overall associations with rejection indices.
- T-cell-mediated rejection showed higher histology indices but lower and more variable dd-cfDNA.
- Increased total cfDNA may help explain why percentage dd-cfDNA was less detectable in low-grade T-cell-mediated rejection.
Disclosure
- Research title:
- dd-cfDNA tracks kidney rejection activity across the continuum
- Authors:
- Louise Benning, Aylin Akifova, Bilgin Osmanodja, Christian Morath, Julia Beck, Ekkehard Schütz, Klemens Budde
- Institutions:
- Heidelberg University, University Hospital Heidelberg, Charité – Universitätsmedizin Berlin, Nuremberg Hospital, Paracelsus Medizinische Privatuniversität, HTG Molecular Diagnostics (United States)
- Publication date:
- 2026-02-24
- OpenAlex record:
- View
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