Session Name: Kidney Acute Antibody Mediated Rejection
Session Date & Time: None. Available on demand.
*Purpose: Extensive literature regarding the utility of donor-derived cell-free DNA (dd-cfDNA) shares various thresholds for active rejection (AR) based on differing data sets for both cellular (TCMR) and antibody-mediated allograft rejection (ABMR) after kidney transplant (KT). Our aim was to independently validate the performance of dd-cfDNA in the context of AR, both in “for cause” but also in the context of surveillance biopsies, the latter typically highlighting detection of subclinical rejection.
*Methods: Patients from the Assessing dd-cfDNA monitoring insights of renal allograft with longitudinal surveillance (ADMIRAL study; clinicaltrials.gov: NCT04566055219) were analyzed with total of 219 biopsies (Bx) and paired plasma dd-cfDNA (AlloSure®; CareDx) from 196 patients (110 “for cause”, 109 “surveillance” Bx). Samples were considered if Bx was performed ≤ 20 days after dd-cfDNA measurement. AR was detected in 107 Bx from 95 patients (65 “for cause”, 42 “surveillance”) and compared to 112 Bx from 108 patients (45 “for cause”, 67 “surveillance”) who did not have AR.
*Results: 74 episodes of ABMR were detected in 66 Patients (39 “for cause”, 35 “surveillance”) and 33 TCMR in 30 patients (26 “for cause”, 7 “surveillance”). The AUC for AR events = 0.77, AUC for ABMR = 0.80 and TCMR = 0.70 [FIGURE 1]. Median level dd-cfDNA with ABMR = 2.1% in “for cause “and 0.91% for “surveillance” Bx [FIGURE 2]. Median level dd-cfDNA with TCMR = 0.85% in “for cause” and 0.52% for “surveillance” Bx. Absence of rejection was associated with median dd-cfDNA = 0.39% in “for cause” and 0.23% for “surveillance” Bx procedures.
*Conclusions: These results independently validate the robust performance characteristics of dd-cfDNA (AlloSure®) as consistent with the published literature ─ for detection of both clinically suspected and subclinical allograft rejection. dd-cfDNA has utility in the detection of both TCMR and ABMR with different patterns of elevation. As these are overlapping and difficult to discriminate, further analysis of Δdd-cfDNA from prior baseline may further optimize use of Bx and enhance histological interpretation.
To cite this abstract in AMA style:Anand S, Pai A, Bromberg JS, Gupta G, Moinuddin I, Alhamad T, Bowers V, Ghosh S, Tian W, Bu L, Stites E. Clinical Validation and Performance of Donor-Derived Cell-Free DNA in Allograft Rejection [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/clinical-validation-and-performance-of-donor-derived-cell-free-dna-in-allograft-rejection/. Accessed June 12, 2021.
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