dd-cfDNA Significantly Improves Rejection Yield in Kidney Transplant Biopsies

Jonathan S. Bromberg, University of Maryland School of Medicine. Electronic address: jbromberg@som.umaryland.edu.
Daniel C. Brennan, Johns Hopkins School of Medicine. Electronic address: dbrenna4@jhmi.edu.
David J. Taber, Medical University of South Carolina. Electronic address: taberd@musc.edu.
Matthew Cooper, Medical College of Wisconsin. Electronic address: macooper@mcw.edu.
Sanjiv Anand, InterMountain Medical Center. Electronic address: sanjiv.anand@imail2.org.
Enver Akalin, Montefiore Medical Center. Electronic address: eakalin@montefiore.org.
Edmund Huang, Cedars-Sinai Medical Center. Electronic address: Edmund.Huang@cshs.org.
Jeffrey A. Klein, University Of Kansas Medical Center. Electronic address: jklein@kumc.edu.
Renata Glehn-Ponsirenas, CareDx, Inc. Electronic address: Rponsirenas@caredx.com.
Jeffrey Rogers, CareDx, Inc. Electronic address: jrogers@caredx.com.
Peale Chuang, CareDx, Inc. Electronic address: pchuang@caredx.com.
Ashish S. Kothari, CareDx, Inc. Electronic address: akothari@caredx.com.
Ling Shen, CareDx, Inc. Electronic address: lshen@caredx.com.
Robert N. Woodward, CareDx, Inc. Electronic address: rwoodward@caredx.com.
Dhiren Kumar, Virginia Commonwealth University. Electronic address: dhiren.kumar@vcuhealth.org.
David Wojciechowski, University of Texas Southwestern. Electronic address: David.wojciechowski@utsouthwestern.edu.
Didier Mandelbrot, University of Wisconsin Medical Center. Electronic address: damandel@medicine.wisc.edu.
Nadiesda Costa, Georgetown University Medical Center. Electronic address: Nadiesda.costa@medstar.net.
Lihong Bu, Mayo Clinic. Electronic address: Bu.Lihong@mayo.edu.
Matthew R. Weir, University of Maryland School of Medicine. Electronic address: MWeir@som.umaryland.edu.

Document Type

Journal Article

Publication Date

8-6-2025

Journal

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

DOI

10.1016/j.ajt.2025.07.2484

Keywords

Biopsy yield; KOAR (Kidney allograft Outcomes Allosure Registry); NCT03326076; Rejection yield; clinical utility of dd-cfDNA; dd-cfDNA; donor derived cell free DNA,; post-kidney transplant biopsy; sub-clinical rejection; surveillance biopsy

Abstract

Donor-derived cell-free DNA (dd-cfDNA) is a biomarker that enables the early detection of immune-mediated graft injury. This study evaluated the clinical utility of dd-cfDNA in predicting the presence of biopsy-proven rejection (BPAR). We analyzed 1,070 biopsies from 1,743 kidney transplant recipients enrolled in the prospective, multicenter Kidney Allograft Outcomes AlloSure Registry (KOAR). Biopsies were grouped into surveillance or for-cause groups and stratified by dd-cfDNA status: elevated, non-elevated, or not tested. Rejection yield was significantly higher when dd-cfDNA was elevated: 39% vs. 7% in the surveillance group and 47% vs. 12% in the for-cause group (p<0.0001). Biopsies with elevated dd-cfDNA and rejection diagnoses more frequently demonstrated ABMR and mixed rejection, whereas biopsies performed with non-elevated dd-cfDNA most often showed no rejection, borderline, or TCMR 1A. The AUROC for BPAR detection was 0.789. These findings demonstrate dd-cfDNA levels can improve the pre-test probability of BPAR in both surveillance and for-cause settings. Therefore, dd-cfDNA can optimize biopsy utilization by identifying renal transplant patients who are most likely to have histological rejection.

Department

Medicine

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