Assessment of Donor-Derived Cell-Free DNA Performance Characteristics Across the Spectrum of TCMR and ABMR After Kidney Transplant

L. Bu¹, S. Anand², A. Pai³, J. S. Bromberg⁴, T. Alhamad⁵, V. Bowers⁶, I. Moinuddin⁷, S. Ghosh⁸, W. Tian⁸, E. Stites⁹, G. Gupta⁷

¹University of Minnesota, Minneapolis, MN, ²Intermountain Medical Center, Murray, UT, ³University of Texas McGovern Medical School, Houston, TX, ⁴University of Maryland School of Medicine, Baltimore, MD, ⁵Washington University in St. Louis, St. Louis, MO, ⁶Tampa General Hospital, Tampa, FL, ⁷Virginia Commonwealth University, Richmond, VA, ⁸CareDx, Brisbane, CA, ⁹University of Colorado, Aurora, CO

Meeting: 2021 American Transplant Congress

Abstract number: 219

Keywords: Histology, Kidney transplantation, Non-invasive diagnosis, Rejection

Topic: Clinical Science » Biomarkers, Immune Assessment and Clinical Outcomes

Session Information

Session Name: Biomarkers, Immune Assessment and Clinical Outcomes - III

Session Type: Rapid Fire Oral Abstract

Date: Monday, June 7, 2021

Session Time: 4:30pm-5:30pm

Presentation Time: 4:40pm-4:45pm

Location: Virtual

*Purpose: Different donor-derived cell-free DNA (dd-cfDNA) thresholds have been reported in association with varying TCMR, ABMR and “Borderline” diagnoses. Interpretation of dd-cfDNA levels spanning active (aABMR) and active-chronic (a/cABMR) is further complicated by presence or absence of C4d staining. We hypothesized that dd-cfDNA levels would complement the pathologic diagnoses.

*Methods: Patients from the Assessing dd-cfDNA monitoring insights of renal allograft with longitudinal surveillance (ADMIRAL study; clinicaltrials.gov: NCT04566055219) were analyzed with a total of 219 biopsies (Bx), centrally interpreted with Banff Categorical and lesion scores, with paired plasma dd-cfDNA (AlloSure®; CareDx) from 196 patients (110 “for cause”, 109 “surveillance”). Samples were considered if Bx performed ≤ 20 days after dd-cfDNA level.

*Results: In analyzing ABMR [FIGURE 1], all aABMR and a/cABMR were associated with significant elevation in dd-cfDNA levels compared to Normal Bx (N=111) median dd-cfDNA level of 0.29% ─ aABMR (C4d+) median: 2.0% (N=12; P=4.9e-05), a/cABMR (C4d+): 1.15% (N=16; P=3.3e-05), aABMR (C4d-): 1.6% (N=8; P=3.2e-04), a/cABMR (C4d-): 1.8% (N=11; P=3.3e-04). No dd-cfDNA difference was observed between C4d+ and C4d- ABMR. No difference in dd-cfDNA levels was observed between ABMR with or without transplant glomerulopathy. For TCMR [FIGURE 2], dd-cfDNA levels were significantly elevated, compared to Normal Bx, for Grade 1A: 1.4% (N=5; P=0.04), 1B: 1.25% (N=8; P=0.01) and 2A: 4.5% (N=3; P=0.003). Intimal arteritis (v) [FIGURE 3] was independently associated with elevated dd-cfDNA levels for v(0) median dd-cfDNA: 0.385% (N=240) and v(>0): 1.7% (P=0.0007).

*Conclusions: dd-cfDNA levels were elevated across the spectrum of active and active-chronic ABMR, regardless of C4d status. Although a rather small ‘N’ for active TCMR cohorts by Grade, there were statistically elevated dd-cfDNA levels and ‘trend’ for correlation for Grade 2A however no difference observed between Grades 1A and 1B. Elevation in dd-cfDNA levels reflected vascular injury in the context of Intimal arteritis (v) lesions.

To cite this abstract in AMA style:

Bu L, Anand S, Pai A, Bromberg JS, Alhamad T, Bowers V, Moinuddin I, Ghosh S, Tian W, Stites E, Gupta G. Assessment of Donor-Derived Cell-Free DNA Performance Characteristics Across the Spectrum of TCMR and ABMR After Kidney Transplant [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/assessment-of-donor-derived-cell-free-dna-performance-characteristics-across-the-spectrum-of-tcmr-and-abmr-after-kidney-transplant/. Accessed November 24, 2024.

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