Donor-derived Cell-free DNA Identifies Antibody-mediated Rejection in Donor Specific Antibody Positive Kidney Transplant Recipients

Stanley C Jordan; Suphamai Bunnapradist; Jonathan S Bromberg; Anthony J Langone; David Hiller; James P Yee; John J Sninsky; Robert N Woodward; Arthur J Matas

doi:10.1097/TXD.0000000000000821

Donor-derived Cell-free DNA Identifies Antibody-mediated Rejection in Donor Specific Antibody Positive Kidney Transplant Recipients

Transplant Direct. 2018 Aug 20;4(9):e379. doi: 10.1097/TXD.0000000000000821. eCollection 2018 Sep.

Authors

Stanley C Jordan¹, Suphamai Bunnapradist², Jonathan S Bromberg³, Anthony J Langone⁴, David Hiller⁵, James P Yee⁶, John J Sninsky⁷, Robert N Woodward⁷, Arthur J Matas⁸

Affiliations

¹ Division of Nephrology, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA.
² Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA.
³ Departments of Surgery and Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD.
⁴ Department of Medicine, Vanderbilt University Medical Center, and Medical Specialties Clinic, Veteran Affairs Hospital Renal Transplant Program, Nashville, TN.
⁵ Biostatistics, CareDx, Inc, Brisbane, CA.
⁶ Clinical Research, CareDx, Inc, Brisbane, CA.
⁷ Research and Development, CareDx, Inc, Brisbane, CA.
⁸ Division of Transplantation, Department of Surgery, University of Minnesota, Minneapolis, MN.

Abstract

Background: Elevated levels of donor-derived cell-free DNA (dd-cfDNA) in the plasma of renal allograft recipients indicates organ injury and an increased probability of active rejection. Donor-specific antibodies (DSA) to HLA antigens are associated with risk of antibody-mediated rejection (ABMR). This study assessed the combined use of dd-cfDNA and DSA testing to diagnose active ABMR.

Methods: Donor-derived cell-free DNA was assayed in 90 blood samples with paired DSA and clinically indicated biopsies from 87 kidney transplant patients. Sixteen cases met criteria for active ABMR. Performance characteristics of dd-cfDNA for diagnosis of active ABMR were determined for samples with prior or current positive DSA (DSA+, n = 33).

Results: The median level of dd-cfDNA (2.9%) in DSA+ patients with active ABMR was significantly higher than the median level (0.34%) in DSA+ patients without ABMR (P < 0.001). The median level of dd-cfDNA in DSA- patients was 0.29%. The positive predictive value of dd-cfDNA (at 1%) to detect active ABMR in DSA+ patients was 81%, whereas the negative predictive value was 83%. The positive predictive value for DSA+ alone was 48%.

Conclusions: The combined use of dd-cfDNA and DSA testing may improve the noninvasive diagnosis of active ABMR in kidney transplant patients. Patients with dd-cfDNA+/ DSA+ results have a high probability of active ABMR.