Abstract
BackgroundAfter transplantation, cell-free DNA derived from the donor organ (ddcfDNA) can be detected in the recipient’s circulation. We aimed to quantify ddcfDNA levels in plasma of kidney transplant recipients thereby investigating the kinetics of this biomarker after transplantation and determining biological variables that influence ddcfDNA kinetics in stable and non-stable patients.Materials and methodsFrom 107 kidney transplant recipients, plasma samples were collected longitudinally after transplantation (day 1–3 months) within a multicenter set-up. Cell-free DNA from the donor was quantified in plasma as a fraction of the total cell-free DNA by next generation sequencing using a targeted, multiplex PCR-based method for the analysis of single nucleotide polymorphisms. A subgroup of stable renal transplant recipients was identified to determine a ddcfDNA threshold value.ResultsIn stable transplant recipients, plasma ddcfDNA% decreased to a mean (SD) ddcfDNA% of 0.46% (± 0.21%) which was reached 9.85 (± 5.6) days after transplantation. A ddcfDNA threshold value of 0.88% (mean + 2SD) was determined in kidney transplant recipients. Recipients that did not reach this threshold ddcfDNA value within 10 days after transplantation showed a higher ddcfDNA% on the first day after transplantation and demonstrated a higher individual baseline ddcfDNA%.ConclusionIn conclusion, plasma ddcfDNA fractions decreased exponentially within 10 days after transplantation to a ddcfDNA threshold value of 0.88% or less. To investigate the role of ddcfDNA for rejection monitoring of the graft, future research is needed to determine causes of ddcfDNA% increases above this threshold value.
Highlights
After transplantation, cell-free DNA derived from the donor organ can be detected in the recipient’s circulation
Cell-free DNA from the donor was quantified in plasma as a fraction of the total cell-free DNA by generation sequencing using a targeted, multiplex polymerase chain reaction (PCR)-based method for the analysis of single nucleotide polymorphisms
Kinetics of the ddcfDNA are less studied after kidney transplantation, as longitudinal data from kidney transplant recipients are currently lacking
Summary
Cell-free DNA derived from the donor organ (ddcfDNA) can be detected in the recipient’s circulation. Its release might be associated with cell damage in the graft thereby indicating a role of ddcfDNA as a biomarker for graft injury after transplantation[1]. Based on prospective data in heart and liver transplant recipients, it is known that a high amount of ddcfDNA is released in the circulation of the transplant recipient in the immediate post-engraftment phase, followed by swift decreases in the plasma fractions of ddcfDNA (proportion of circulating cell-free DNA that is donor-derived) approximately one week after transplantation[2, 3]. We aimed to quantify ddcfDNA levels in plasma of kidney transplant recipients thereby investigating the kinetics of this biomarker after transplantation and determining biological variables that influence ddcfDNA kinetics in stable and non-stable patients
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