Donor-Derived Cell-Free DNA as a Biomarker of T Cell Mediated Rejection in Pediatric Kidney Transplant Patients

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: 111

Keywords: Kidney transplantation, Pediatric

Topic: Clinical Science » Kidney » 43 - Kidney: Pediatrics

Session Information

Session Name: Kidney: Pediatrics

Session Type: Rapid Fire Oral Abstract

Date: Sunday, June 5, 2022

Session Time: 5:30pm-7:00pm

Presentation Time: 6:40pm-6:50pm

Location: Hynes Ballroom C

*Purpose: T-cell-mediated rejection (TCMR) is a major cause of kidney allograft failure which requires kidney biopsy for a definitive diagnosis. Donor-derived cell-free DNA (dd-cfDNA) is an emerging biomarker used to assess kidney allograft injury, with scant pediatric data. This study was conducted to investigate the accuracy of dd-cfDNA as a non-invasive marker of TCMR in a pediatric kidney transplant population.

*Methods: In this retrospective single-center observational study, we studied 63 patients who had concurrent 123 dd-cfDNA levels along with kidney biopsies within the first year post-transplant that showed either TCMR or normal, all other pathologies were excluded and we had no ABMR before month 12. We included both surveillance biopsies (3, 6 and 12 months) and diagnostic biopsies. 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). Treating each sample as independent, we divided the 123 biopsy samples with concurrent dd-CFDNA levels into two groups (no evidence of TCMR vs Any TCMR, including subclinical rejection) and analyzed the data.

*Results: The median (IQR) of dd-cfDNA in TCMR group(n=30) of 0.55% (0.29-1.18%) was significantly higher than 0.21% (0.13-0.46 %) in non-TCMR (n= (93) (p < 0.001; Figure) by Mann-Whitney U test. The area under the curve was 0.73 (95% CI, 0.62 to 0.84: Figure). With a cutoff of 1.0%, dd-cfDNA had a 95.7% specificity (95% CI, 89.5% to 98.3%) and 30% sensitivity (95% CI, 16.7% to 47.9%) to discriminate TCMR from no rejection. With a cutoff of 0.5%, dd-cfDNA had a 80% specificity (95% CI, 71.5 to 87.4) and 56.7% sensitivity (95% CI, 39.2% to 72.62%) to discriminate TCMR from no rejection.

*Conclusions: Our data show that pediatric patients have a similar high AUC and specificity to the 0.74 AUC and 83% specificity shown in the adult DART study (Bloom et al, JASN 2017). But the sensitivity in children was lower than the 81% in DART, perhaps related to allograft size mismatch that may elevate some dd-cfDNA levels without injury

To cite this abstract in AMA style:

Dandamudi R, Federman S, Woodward R, Dholakia S, Walther L, Dharnidharka V. Donor-Derived Cell-Free DNA as a Biomarker of T Cell Mediated Rejection in Pediatric Kidney Transplant Patients [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-derived-cell-free-dna-as-a-biomarker-of-t-cell-mediated-rejection-in-pediatric-kidney-transplant-patients/. Accessed November 23, 2024.

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