Abstract:
Introduction: Monitoring allograft rejection is crucial for improving long-term transplant outcomes,
Standard monitoring often fails to detect subclinical injury, leading to irreversible graft loss. Recently,
non-invasive biomarkers, specifically donor-derived cell-free DNA (dd-cfDNA) and donor-specific
antibodies (DSA), have appeared as accurate tools for early identification of acute and antibodymediated rejection (AMR).
Material and Methods: We conducted an integrative review of literature indexed in PubMed and
Scopus published between 2017 and 2025. The search focused on prospective cohorts and metaanalyses evaluating kidney and heart transplant recipients. Key performance indicators analyzed
included Area Under the Receiver Operating Characteristic (AUROC) curves, sensitivity, specificity,
and Negative Predictive Value (NPV).
Results: Data synthesis across multiple organ cohorts reveals that dd-cfDNA maintains a diagnostic
AUROC range of 0.75–0.86 for identifying allograft injury. Individual kidney studies typically report
sensitivity between 59%-82%, with specificity often exceeding 80%. In heart transplantation,
sensitivity varies (60–78%), and the NPV remains consistently high at 90–97%, providing a robust
“rule-out” capability for acute rejection. DSA positivity was found to be a consistent clinical “red flag”,
associated with a 2.5 to 4-fold increased risk of AMR. The integration of both biomarkers, using ddcfDNA to verify the injury suspected by DSA, yielded superior risk stratification than either marker
used in isolation.
Conclusions: The evidence from 2017–2025 indicates that dd-cfDNA and DSA are highly
complementary. Their integration into clinical practice offers a reliable, non-invasive alternative for
identifying early allograft injury. Future efforts should focus on refining organ-specific thresholds to
standardize clinical decision-making across diverse transplant populations.
