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Donor-Derived Cell-Free DNA Trends Before and After Rejection Vary Based on Timing of Rejection

C. Rebello1, K. Guo1, S. Park2, B. Kinsella1, L. Zhao1, J. Friedewald1

1Northwestern University, Chicago, IL, 2Transplant Nephrology, Northwestern University, Chicago, IL

Meeting: 2022 American Transplant Congress

Abstract number: 1559

Keywords: Genomic markers, Kidney transplantation, Rejection

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) has been used for acute rejection detection and trending levels may help predict future rejection and assess the adequacy of therapy post rejection. We sought to determine if trends in dd-cfDNA were different depending on the timing of rejection post kidney transplant. The purpose of this study was to discover and examine dd-cfDNA variation observed in subclinical and clinical rejection occurring at three different stages over a period of 2 years post-transplant.

*Methods: The study cohort consisted of 107 distinct subjects having biopsies for stable and unstable kidney function at different intervals of the study. 148 blood samples were paired with surveillance or indication biopsies. dd-cfDNA using the TRAC assay was reported as the proportion of dd-cfDNA. We assessed the slope of dd-cfDNA and rejection timings by generating a scatter plot using a loose smooth curve and a linear mixed effect model to compare the dd-cfDNA result slope at three different rejection time intervals -month 2 to month 6, at month 12, and at month 24 each with a before and after 180 days dd-cfDNA results.

*Results: Log transformed (dd-cf DNA) had positive slope in all groups prior to rejection. Slopes after rejection did not show significant difference in subjects with rejection (n=38) between 2 and 6 months post transplant (p value = 0.66) (Figure 1). At month 12 rejection (n=60), the slope of log (dd-cfDNA) trended downward (p value = 0.07) after the rejection (Figure 2). Significant log (dd-cfDNA) slope changes were observed before and after 24 months rejection (p value = 0.01) (Figure 3). The variation in slope is observed at three different rejection time intervals with later rejection showing a steep decline.

*Conclusions: In this study, we demonstrated varying changes in the slope of dd-cfDNA before and after rejection at different times post-transplant. These data suggest that further study is needed to determine the utility of dd-cfDNA trends in patient monitoring in different settings.

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To cite this abstract in AMA style:

Rebello C, Guo K, Park S, Kinsella B, Zhao L, Friedewald J. Donor-Derived Cell-Free DNA Trends Before and After Rejection Vary Based on Timing of Rejection [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-derived-cell-free-dna-trends-before-and-after-rejection-vary-based-on-timing-of-rejection/. Accessed May 30, 2025.

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