Plasma Donor-Derived Cell-Free DNA Longitudinal Kinetics After Kidney Transplantation in Children
1Pediatrics, Washington University School of Medicine in St. Louis, St. Louis, MO, 2CareDx, Brisbane, CA
Meeting: 2022 American Transplant Congress
Abstract number: 1576
Keywords: Kidney transplantation, Pediatric
Topic: Basic Science » Basic Clinical Science » 17 - Biomarkers: Clinical Outcomes
Session Information
Session Name: Biomarkers: Clinical Outcomes
Session Type: Poster Abstract
Date: Tuesday, June 7, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: 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) Our aim was to determine if children would have similar kinetics, given the size mismatch between adult sized allografts and smaller sized recipients.
*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 cohortcohort, 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-year's 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-cf DNA 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.
*Conclusions: 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.
To cite this abstract in AMA style:
Dandamudi R, Federman S, Woodward R, Dholakia S, Walther L, Dharnidharka V. Plasma Donor-Derived Cell-Free DNA Longitudinal Kinetics After Kidney Transplantation in Children [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/plasma-donor-derived-cell-free-dna-longitudinal-kinetics-after-kidney-transplantation-in-children/. Accessed October 6, 2024.« Back to 2022 American Transplant Congress