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Donor-Derived Cell-Free DNA (dd-cfDNA) for Assessment of Response After Treatment of Allograft Rejection

R. Gohh1, J. Klein2, M. Jagadeesan3, V. Rao4, M. Weir5, H. Gilligan6, G. Shekhtman7, N. Agrawal8, Y. Fu9, E. Akalin10

1Alpert School of Medicine, Brown University, Providence, RI, 2University of Kansas Medical Center, Kansas City, KS, 3George Washington School of Medicine, Washington, DC, 4Medical University of South Carolina, Charleston, SC, 5University of Maryland, Baltimore, MD, 6Massachusetts General Hospital, Boston, MA, 7CareDx Inc., Brisbane, CA, 8CareDx Inc, Brisbane, CA, 9CareDx, Brisbane, CA, 10Montefiore Medical Center, Bronx, NY

Meeting: 2022 American Transplant Congress

Abstract number: 1675

Keywords: Glomerular filtration rate (GFR), Immunosuppression, Kidney transplantation, Rejection

Topic: Clinical Science » Kidney » 34 - Kidney: Acute Cellular Rejection

Session Information

Session Name: Kidney: Acute Cellular Rejection

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: Surveillance of dd-cfDNA after therapy for rejection represents a promising strategy for monitoring post-treatment response. We assessed post-rejection kinetics of dd-cfDNA among kidney transplant recipients in the Kidney allograft Outcomes AlloSure Registry (KOAR, NCT03326076).

*Methods: We identified patients with biopsy-proven allograft rejection (BPAR), defined as ABMR, TCMR, or Mixed (Banff 2019), biopsy-paired dd-cfDNA measurements (within ≤30d of biopsy), and follow-up results 60-150 days after BPAR. When available, treatment and follow-up histology data was also analyzed.

*Results: 48 episodes of BPAR (24 TCMR, 19 ABMR, 5 Mixed) and paired dd-cfDNA results were identified in 42 patients [Table 1]. Overall, a significant reduction was seen between the median index (1.36%, IQR: 0.29-2.25) and follow-up dd-cfDNA results (0.35%, IQR: 0.13-0.95; p < 0.01) [Figure 1a]. For patients with concurrent eGFR measurements, no statistically significant improvement was seen. These patterns held when analysis was limited to TCMR and ABMR/Mixed rejections [Figure 1b, 1c]. 7 patients (2 ABMR, 4 TCMR, and 1 Mixed; median index dd-cfDNA 1.15%, IQR: 0.31-2.46) had repeat biopsies within 30 days of their follow-up testing; 1 patient with acute ABMR had chronic active ABMR on repeat biopsy, with a dd-cfDNA of 1.86%, while the remainder had either no rejection or borderline findings (median dd-cfDNA 0.74%, IQR: 0.30-2.59).

*Conclusions: Our findings highlight that reduction in dd-cfDNA is commonly seen following BPAR, suggesting that most patients experience a “molecular response” to therapy. Studies are needed to better understand the prognostic significance of a molecular response and how persistent elevations in dd-cfDNA after treatment should guide subsequent management.

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To cite this abstract in AMA style:

Gohh R, Klein J, Jagadeesan M, Rao V, Weir M, Gilligan H, Shekhtman G, Agrawal N, Fu Y, Akalin E. Donor-Derived Cell-Free DNA (dd-cfDNA) for Assessment of Response After Treatment of Allograft Rejection [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-derived-cell-free-dna-dd-cfdna-for-assessment-of-response-after-treatment-of-allograft-rejection/. Accessed May 11, 2025.

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