Donor-Derived Cell-Free DNA for Detection of Cell-Mediated Rejection in Low Risk Kidney Transplant Patients
Intermountain Medical Center, Murray, UT
Meeting: 2020 American Transplant Congress
Abstract number: C-347
Keywords: Kidney
Session Information
Session Name: Poster Session C: 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 emerging non-invasive biomarker for kidney allograft rejection. This has not been externally validated in low risk population. We describe our experience of dd-cfDNA for detecting and discriminating rejection.
*Methods: Serial dd-cfDNA samples were obtained in the context of routine clinical care at months 1,2,3,4, 6, 9 and 12 months post-transplant in the 1st year post-transplant (Tx) and every 3 months thereafter. Patients with dd-cfDNA within 30 days of Kidney allograft biopsies that were performed on a “for-cause” basis to assess for biopsy proven acute rejection (BPAR) were included in the study. Some patients had multiple biopsies;each biopsy was treated as a separate event. Receiver operating characteristic curves (ROC) for any rejection (AR), Cell Mediated rejection (CMR), and antibody mediated rejection (AMR) were generated. Borderline cellular rejection were included as CMR.
*Results: Of 39 patients, mean age ,49 years, 29 , males, 10% had pre-existing Donor specific antibody (DSA) less than 4000 MFI, mean calculated Panel Reactive Antibody (cPRA) was 20%, 18% were re-transplants. 59% of patients did have BPAR. Of 62 events of biopsy recorded, 56% were CMR, through the study course, 9% were AMR. Discrimination for AR (AUC 0.64 (CL: 0.49-0.78)), CMR (AUC 0.61 (CL:0.47-0.76)), and AMR (AUC 0.88, CL: (0.73-1)) (fig 1). For CMR- Banff- 2a, the AUC was better at 0.74 (CL 0.6-0.88) than all CMR (AUC 0.61 (CL:0.47-0.76)) (fig2). A dd-cfDNA threshold ≥1.0% for AR yielded a PPV of 75.0% and NPV 42.0%; for CMR yielded a PPV of 66.7% and NPV of 42.6%; for AMR yielded a PPV of 25.0% and NPV of 91.33%.
*Conclusions: We show that in low risk transplant population dd-cfDNA has poor discrimination across low-grade CMR. Severity of CMR did increase the discrimination for the test consistent with a low NPV. Results suggest that validity and utility of dd-cfDNA in detecting low grade CMR is low with current cutoff values.
To cite this abstract in AMA style:
Anand S, Dong L, Fife M, Krong J, Dow S, Morris D, Srinivas T. Donor-Derived Cell-Free DNA for Detection of Cell-Mediated Rejection in Low Risk Kidney Transplant Patients [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/donor-derived-cell-free-dna-for-detection-of-cell-mediated-rejection-in-low-risk-kidney-transplant-patients/. Accessed June 6, 2025.« Back to 2020 American Transplant Congress