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Virtual Abstracts to assigned to Sessions

Monday October 21, 2024 - 12:00 to 14:00

Room: TBD

V-212.2 Enhancing Pediatric Kidney Transplant Rejection Detection: Integrating Donor-derived Cell-free DNA Fraction and Quantity.

Raja Dandamudi, United States

Assistant Professor
Pediatric Nephrology
Washington University School of Medicine in St.Louis.

Abstract

Enhancing pediatric kidney transplant rejection detection: Integrating donor-derived cell-free DNA fraction and quantity

Raja Dandamudi1, Lujain Jaza1, Mansi Agarwal2, Charles Goss2, Vikas R Dharnidharka1.

1Pediatrics, Washington University School of Medicine, St.Louis, MO, United States; 2Biostatistics, Washington University School of Medicine, St.Louis, MO, United States

Background: Donor‐derived cell‐free DNA (dd‐cfDNA) is a noninvasive peripheral blood biomarker for the monitoring of allograft integrity in kidney transplantation. The % dd-cfDNA is expressed as the percent of donor DNA to total (donor plus recipient) cfDNA. % dd-cfDNA may be influenced by fluctuations in recipient cfDNA, presenting a potential drawback. This challenge can be addressed through the absolute quantification of dd-cfDNA, such as measuring genomic copies of dd-cfDNA per milliliter of the patient's plasma [cp/mL].In this study, we compared the relative predictive power of each of these variables to the combination of the two, in detecting transplant rejection in pediatric patients.
Methods: In this retrospective single-center observational study, we studied 55 patients (M: F 33:22) who had concurrent 106 dd-cfDNA levels along with kidney biopsies within the three years post-transplant. We included both surveillance biopsies (3, 6 and 12 months post-transplant) and diagnostic biopsies. We quantified dd-cfDNA in plasma as a % fraction of the total cell-free DNA and absolute dd-cfDNA (copies/ml) by next generation sequencing using a targeted, multiplex PCR-based method for the analysis of single nucleotide polymorphisms (AlloSure, CareDx, Brisbane, CA). Treating each sample as independent, we divided the 107 biopsy samples with concurrent dd-cfDNA levels into two groups (no evidence of rejection vs any rejection including subclinical rejection) and analyzed the data.
Results: In patients (n = 26 samples) with biopsy‐proven rejection, median dd‐cfDNA (cp/mL) was 6 fold higher and median % dd‐cfDNA 4‐fold higher (90 cp/mL; 0.93%, respectively) than medians in stable phase patients (n = 80 samples) without rejection (15 cp/mL; 0.22%). The AUC of % dd-cfDNA alone to identify rejection was 0.84, the absolute quantification of dd-cfDNA alone was 0.87 and combined AUC improved to 0.89.
Conclusion: In this retrospective biopsy-matched, dd-cfDNA study in pediatric kidney transplant patients the combination of dd-cfDNA fraction and quantity was more powerful than either dd-cfDNA fraction or quantity alone.

References:

[1] Biomarkers
[2] Pediatric Nephrology
[3] Rejection

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