40 - Plasma donor-derived cell-free DNA longitudinal kinetics after kidney transplantation in children

Poster Number: 40
Publication Number: 40.235

Raja Dandamudi, Washington University in St. Louis School of Medicine, St. Louis, MO, United States; Stuart D. Federman, CareDx, Saint Louis, MO, United States; Robert N. Woodward, CareDx, South San Francisco, CA, United States; Shamik Dholakia, CareDx, San Francisco, CA, United States; Leslie Walther, Washington University in St. Louis, St. Louis, MO, United States; Vikas R. Dharnidharka, Washington University in St Louis, Creve Coeur, MO, United States

Background: Donor-derived cell-free DNA (dd-cfDNA) are DNA fragments released continuously into circulation from injured donor allograft cells. In adult studies, the levels drop to a mean of 0.46% (± 0.21%) approximately 10 days after transplantation. {Gielis, 2018 #154}

Objective: Our aim was to determine if children would have similar kinetics, given the size mismatch between adult sized allografts and smaller sized recipients.

Design/Methods: We accessed a biobank of 71 children with longitudinally collected and banked plasma samples monthly, drawn between 30 days and 12 months post-kidney transplant from 2013 onwards. We quantified dd-cfDNA 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 (AlloSure, CareDx, Brisbane, CA). A subgroup of 204 samples from 54 stable renal transplant recipients with no major infectious events, rejection events or delayed graft function were identified to study the dd-cfDNA kinetics over time.

Results: In the cohort, the median (25-75% percentile) plasma % dd-cfDNA at 30 days post renal transplant was 0.84 (0.64 - 1.2) %, decreasing to 0.43% (0.25 - 0.66) % by month 2 and to a median of 0.23 (0.16 - 0.32) % by month 6. When further stratifying into 2 groups based on the recipient age at transplant, in comparison to the >10 years group (137 samples), the < 10-years recipient age group (67 samples) had greater mean % dd-cfDNA in the entire first year post transplant. In the < 10-year age group the median % dd-cfDNA did not reach < 0.2% till 12 months post-transplant whereas in the >10 years age group the mean % dd-cfDNA reached < 0.2% by 4 months post-transplant.Conclusion(s): In conclusion, % dd-cfDNA levels post-transplant are higher for a longer time in children versus adults. We attribute this difference to increased dd-cfDNA from the allograft and lower background self-cf-DNA from the lower body mass index of recipients. Relatively small sample size and retrospective design are study limitations. Whether absolute or total dd-cfDNA levels would be more useful in children is worthy of study.
Plasma donor-derived cell-free DNA longitudinal kinetics after kidney transplantation in children