Variability and longitudinal dynamics of donor-derived cell-free DNA in kidney and liver recipients: a comparison of absolute and relative quantities in plasma and urine.

Background: Donor-derived cell-free DNA (ddcfDNA) is increasingly being integrated into clinical practice for detecting allograft rejection in solid organ recipients. Natural fluctuations in ddcfDNA or other conditions can affect interpretation. Therefore, we investigated ddcfDNA trends in kidney (KT) and liver (LT) recipients over the first 2 years post-transplantation, assessing intra- and inter-individual variability in absolute and relative quantities. Additionally, we analysed urinary ddcfDNA in KT alongside plasma ddcfDNA and other biomarkers. Methods: Blood and urine from KT and LT were collected longitudinally at regular visits. Mismatched Results: We found comparable inter- and intra-individual variability in stable KT plasma for both absolute and fractional ddcfDNA. In stable and nonstable LT plasma, intra-individual variability accounted for most of the total variance. Urinary ddcfDNA in KT showed inter-sex variability in fractional quantities. Conclusions: The large contribution of intra-individual variability suggests including individual ddcfDNA dynamics in addition to fixed cut-offs for the detection of allograft injury. In LT and urinary ddcfDNA in KT, ddcfDNA_cpml should be considered alongside ddcfDNA%, as they seem to directly represent the allograft status.