Donor-Derived Cell-Free DNA Levels During Early Rejection after Kidney Transplant May Be Impacted by Type of Induction Agent Received
Cedars-Sinai, Los Angeles, CA
Meeting: 2020 American Transplant Congress
Abstract number: B-320
Keywords: Induction therapy, Kidney transplantation, Monitoring, Rejection
Session Information
Session Name: Poster Session B: Biomarkers, Immune Assessment and Clinical Outcomes
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*Purpose: Donor-derived cell-free DNA (dd-cfDNA) is an injury biomarker that detects rejection in kidney transplant recipients (KTR). It is reported as % cfDNA from the allograft within the overall level of cfDNA in the recipient. It is currently unknown if dd-cfDNA is impacted by therapies that may increase a KTR’s own cfDNA, such as depleting induction that cause cellular lysis. We herein compare the distribution of dd-cfDNA (Allosure©) during the 1st month post-Tx between induction in both de novo and repeat KTR with vs. without biopsy proven acute rejection (BPAR).
*Methods: 175 dd-cfDNA samples in the1st month post-Tx from 154 KTR were stratified based on induction. We further stratified based on BPAR within the 1st month post-Tx and assessed de novo vs. repeat KTR with a prior allograft in situ separately. KTR without Bx were presumed to have no rejection given our practice to only perform for cause Bx. Repeat KTR at our program only receive alemtuzumab (C1H) induction.
*Results: Of the 147 dd-cfDNA samples in de novo KTR, 27 had BPAR. In de novo KTR without BPAR, dd-cfDNA was similar between induction (Fig 1) with a median of 0.34%, 0.43% and 0.33 in C1H, thymoglobulin (ATG) and basiliximab (IL2) groups, respectively. In de novo KTR with BPAR, dd-cfDNA was lower in C1H vs. ATG or IL2 (Fig 2) with a median of 1.1%, 1.8% and 2.1%, respectively. Of 28 dd-cfDNA samples in repeat KTR who received C1H, 5 had BPAR. Median dd-cfDNA was 0.6% and 0.95% in those without and with BPAR, respectively.
*Conclusions: In de novo KTR without BPAR during the 1st month post-Tx, induction did not impact dd-cfDNA. However, in de novo KTR with BPAR, dd-cfDNA was lower in KTR who received depleting induction, particularly C1H, vs non-depleting agent. Furthermore, C1H was associated with surprisingly low dd-cfDNA levels in repeat KTX with BPAR, which is a population where increased dd-cfDNA is expected as the previous allograft also contributes to the level. This indicates that depleting induction may increase recipient cfDNA release via cellular lysis and thereby lower the proportion of dd-cfDNA during BPAR. Thus, induction therapies may need to be considered more carefully when interpreting dd-cfDNA in KTR with early BPAR.
To cite this abstract in AMA style:
Gillespie M, Lim K, Vo A, Huang E, Ammerman N, Peng A, Najjar R, Sethi S, Jordan S. Donor-Derived Cell-Free DNA Levels During Early Rejection after Kidney Transplant May Be Impacted by Type of Induction Agent Received [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-derived-cell-free-dna-levels-during-early-rejection-after-kidney-transplant-may-be-impacted-by-type-of-induction-agent-received/. Accessed May 11, 2025.« Back to 2020 American Transplant Congress