Investigation of donor-derived cell-free DNA kinetics in stable renal transplant recipients

E.M. Gielis, K. Ledeganck, A. Dendooven, P. Meysman, K. Laukens, J. de Schrijver, S. van Laecke, M.P. Emonds, M. Vinckx, P. Aerts, B. de Winter, J.L. Bosmans, J. Del Favero, D. Abramowicz

Friday 16 march 2018

11:50 - 12:00h at Willem Burger Zaal

Categories: Clinical, Session (parallel)

Parallel session: Parallel session 13: Clinical

Background

After kidney transplantation, cell-free DNA derived from the donor organ (ddcfDNA) can be detected in the recipient’s circulation. In the context of an investigation looking at the value of ddcfDNA as an early marker of cell injury and rejection, we first aimed to determine the kinetics of plasma ddcfDNA in a group of stable transplant recipients thereby investigating a model to predict the ddcfDNA fraction from day 1 after transplantation.

Methods

Stable renal transplant recipients were selected from a cohort of 107 recipients within a multicenter longitudinal study based on the following criteria: absence of acute kidney injury, no need of indication biopsies or dialysis and the presence of a normal protocol biopsy if available. Plasma was collected from day 1 until 3 months after transplantation and ddcfDNA was quantified by NGS as a fraction of total cell-free DNA by using a targeted, multiplex PCR based method for the analysis of donor specific SNPs. Clinical parameters of the recipient, donor and transplantation together with histological parameters of the time zero biopsy were included in a biostatistical elastic net regression analysis to create a prediction model for the ddcfDNA% on day 1. For each follow-up time point, median ddcfDNA fractions were calculated.

Results

40 renal transplant recipients were identified as ‘stable graft recipients’ according to the predetermined criteria. On the first day after transplantation, median ddcfDNA fractions were 10.57% ranging from 1.71% to 38.99%. Median fractions then decreased to 2.39% and 0.66% respectively on day 3 and 7 after transplantation. Four parameters were determined as independent predictors for the ddcfDNA% on day 1: we found a positive correlation with 1. the administration of an IL-2R antagonist induction therapy (vs ATG); 2. higher residual diuresis of the recipient before transplantation and 3. the presence of chronic interstitial damage on the time zero biopsy. The time interval after transplantation correlated negatively with the ddcfDNA% on day 1.

Conclusion

After transplantation, ddcfDNA fractions reach a low baseline level within the first week after transplantation in stable transplant recipients. Four parameters were identified as independent predictors for the ddcfDNA% on the first day after transplantation.