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Plasma Donor-Derived Cell-Free DNA Longitudinal Kinetics After Kidney Transplantation in Children

R. Dandamudi1, S. Federman2, R. Woodward2, S. Dholakia2, L. Walther1, V. Dharnidharka1

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.

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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 May 30, 2025.

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