GRAVER A1,2, POWER D1,2,3, WHITLAM J1,2
1Department of Nephrology, Austin Health, Heidelberg, Australia, 2Department of Medicine (Austin Health), Melbourne Medical School, University of Melbourne, Heidelberg, Australia, 3Kidney Laboratory, Institute for Breathing and Sleep, Austin Health, Heidelberg, Australia
Aims: To examine whether plasma cell-free DNA (cfDNA) at the time of indication allograft biopsy predicts longer-term graft and kidney transplant recipient (KTR) outcomes.
Background: Studies investigating the role of cfDNA in kidney allograft dysfunction have primarily focused on the ability of donor-derived cfDNA (ddcfDNA) to detect rejection. In our earlier studies, higher plasma ddcfDNA levels were diagnostic of antibody-mediated rejection (ABMR). As ABMR is an established determinant of long-term graft outcomes, we hypothesised that higher levels of ddcfDNA would associate with poorer outcomes.
Methods: We conducted a retrospective review of KTRs who had plasma cfDNA measurements, including ddcfDNA, at the time of indication allograft biopsies between October 2014 and March 2017, and correlated these against functional and survival outcomes after six-years follow-up.
Results: The cohort included 37 KTRs with functioning grafts, 6 KTRs with failed grafts, and 6 deceased KTRs (including 4 deaths with functioning grafts). There was no association between absolute ddcfDNA levels and KTR or allograft survival. Lower ddcfDNA graft fraction (ddcfDNA/total cfDNA; 0.21% vs 0.52%, p=0.047) and higher total cfDNA (4736.6cp/ml vs 1639.91cp/ml, p=0.04) were observed in KTRs that died within the follow-up period. Higher ddcfDNA graft fraction (0.78% vs 0.44%, p=0.01) and lower total cfDNA (912.43cp/ml vs 1803.09cp/ml, p=0.02) were observed for allografts that failed (death-censored) during the follow-up period.
Conclusions: Higher distribution of total cfDNA in KTRs that later died, and lower distribution of total cfDNA in KTR allografts that were later lost, was unexpected and has not been previously reported. Total cfDNA has been described as a prognostic marker for illness severity and patient outcomes in critical care. Further studies are required to confirm these findings in KTRs.
Dr Alison Graver graduated from the University of Tasmania in 2012, and completed advanced training in adult nephrology (FRACP) at Austin Health in 2019. She currently practises in general and transplant nephrology at Austin Health, and is undertaking a PhD through the University of Melbourne, examining non-invasive monitoring of kidney transplant recipients.