Donor-Derived Cell-Free DNA May Not Discriminate Rejection in Kidney Transplant Recipients with a Prior Allograft in Place
Cedars-Sinai, Los Angeles, CA
Meeting: 2020 American Transplant Congress
Abstract number: B-318
Keywords: High-risk, Kidney transplantation, Rejection, Retransplantation
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 discriminating rejection in kidney transplant (KTx) patients (pts). However, its performance when stratified by rejection risk (i.e. standard vs. high) is largely unknown. We investigated the performance of dd-cfDNA (AlloSure©; CareDx, Inc,; Brisbane, CA) in standard- and high-risk KTx pts.
*Methods: We identified 195 KTx pts assessed with dd-cfDNA for rejection suspicion within 1 month of KTx biopsy. 84 were defined as high-risk (positive x-match at Tx, historical DSA or DSA at Tx, or presence of DSA at dd-cfDNA assessment) and the remaining 111 were standard-risk. Receiver operating characteristic curves (ROC) for any rejection and the areas under the ROC curve (AUC) were calculated for both groups.
*Results: dd-cfDNA distribution was higher in standard-risk pts with borderline cell-mediated rejection (CMR; n=15) and CMR (n=24) vs. no rejection (n=72), whereas there was no difference in high-risk pts with no rejection (n=29), borderline CMR (n=11), and CMR (n=10) (Fig. 1). However, dd-cfDNA was higher in cases of antibody-mediated rejection (ABMR; n=34) vs. no rejection (p=0.01). dd-cfDNA discriminated rejection in standard-risk pts (Fig. 2a; AUC: 0.71, 95% CI: 0.61-0.82), but poorly discriminated rejection in high-risk pts (Fig. 2b; AUC: 0.59, 95% CI: 0.46-0.73). Failure to discriminate rejection in high-risk pts was influenced by having a prior KTx. Among high-risk pts with a prior KTx (n=28), dd-cfDNA did not discriminate rejection (Fig. 2c; AUC: 0.43, 95% CI: 0.20-0.65). However, discrimination of rejection in high-risk pts without a prior KTx (n=56) was similar to standard-risk pts (Fig. 2d; AUC: 0.73; 95% CI: 0.56-0.90).
*Conclusions: dd-cfDNA discriminates rejection similarly in standard- and primary high-risk KTx pts, but may fail to discriminate rejection when a prior KTx is in situ. It is possible that derivation of a correction factor for a prior KTx may improve the ability of dd-cfDNA to discriminate rejection in re-Tx pts. Future studies in prior KTx pts on dialysis aimed at establishing baseline dd-cfDNA levels due to a failed allograft and larger validation studies of dd-cfDNA among re-Tx pts are necessary.
To cite this abstract in AMA style:
Vo A, Gillespie M, Jordan SC, Peng A, Najjar R, Sethi S, Lim K, Ammerman N, Huang E. Donor-Derived Cell-Free DNA May Not Discriminate Rejection in Kidney Transplant Recipients with a Prior Allograft in Place [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-derived-cell-free-dna-may-not-discriminate-rejection-in-kidney-transplant-recipients-with-a-prior-allograft-in-place/. Accessed May 11, 2025.« Back to 2020 American Transplant Congress