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Donor-Derived Cell-Free DNA as a Non-Invasive Readout of Activity Across the Rejection Continuum
Louise Benning1, Aylin Akifova2, Bilgin Osmanodja2
1Department of Nephrology, Heidelberg University Hospital, Heidelberg, Germany.
Summary
Donor-derived cell-free DNA (dd-cfDNA) tracks kidney transplant rejection severity. This non-invasive marker complements histopathology, extending the rejection continuum concept to blood tests for better graft monitoring.
Area of Science:
- Nephrology
- Transplant Immunology
- Molecular Diagnostics
Background:
- Kidney allograft rejection is a biological continuum quantified by histopathology indices.
- Donor-derived cell-free DNA (dd-cfDNA) is a potential non-invasive biomarker for transplant health.
Purpose of the Study:
- To determine if dd-cfDNA reflects the kidney transplant rejection continuum.
- To assess if dd-cfDNA complements histopathology-derived rejection indices.
Main Methods:
- Analysis of dd-cfDNA (percentage, absolute copies/mL, combined CM score) against histopathology indices in 249 indication biopsies from two cohorts.
- Interclass correlation analyses to assess associations between dd-cfDNA measures and rejection indices.
Main Results:
- dd-cfDNA levels increased with histopathological activity, highest in antibody-mediated rejection (AMR) and mixed rejection.
- T-cell-mediated rejection (TCMR) showed more variable dd-cfDNA, potentially due to increased total cfDNA.
- The combined dd-cfDNA CM score demonstrated the strongest association with rejection indices (sum R² = 3.4).
Conclusions:
- dd-cfDNA serves as a non-invasive readout of kidney allograft inflammation.
- dd-cfDNA extends the rejection continuum concept into non-invasive monitoring, complementing histopathology.
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