Plasma Donor-Derived Cell-Free DNA Levels Risk-Stratify Kidney Allograft Injury with Isolated Transplant Glomerulitis

L. Bu¹, S. Anand², A. Pai³, J. S. Bromberg⁴, G. Gupta⁵, I. Moinuddin⁵, T. Alhamad⁶, V. Bowers⁷, S. Ghosh⁸, W. Tian⁸, E. Stites⁹

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, ⁵Virginia Commonwealth University, Richmond, VA, ⁶Washington University in St. Louis, St. Louis, MO, ⁷Tampa General Hospital, Tampa, FL, ⁸CareDx, Brisbane, CA, ⁹University of Colorado, Aurora, CO

Meeting: 2021 American Transplant Congress

Abstract number: 1028

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

Topic: Clinical Science » Kidney » Kidney Acute Antibody Mediated Rejection

Session Information

Session Name: Kidney Acute Antibody Mediated Rejection

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*Purpose: The Banff lesion Glomerulitis (g) characterizes the degree of microvascular glomerular inflammation. Some studies have demonstrated glomerulitis in the absence of C4d in association with donor-specific HLA antibodies (DSA). The clinical significance of “isolated glomerulitis” has not been adequately studied in light of heterogenous clinical outcomes and “equivocal” Banff lesion scores. We hypothesized that quantification of molecular inflammation with donor-derived cell-free DNA (dd-cfDNA) may permit risk-stratification of (g).

*Methods: 263 KT biopsies with paired dd-cfDNA levels (AlloSure®; CareDx, Inc.) were examined from the Assessing AlloSure dd-cfDNA monitoring insights of renal allograft with longitudinal surveillance (ADMIRAL Study, clinicaltrials.gov: NCT04566055219). Paired biopsies performed ≤ 20 days after the dd-cfDNA level consisted of both “protocol” and “for cause”. Pathology reports were centrally interpreted and scored. Correlations with histology lesion and dd-cfDNA levels were performed; high dd-cfDNA was defined as >0.5% based on previous injury analysis for ADMIRAL cohort. Isolated glomerulitis was assessed using Banff 2018 with g(0):no glomerulitis, g(1): segmental or global glomerulitis < 25% glomeruli, g(2):25-75% and g(3): >75% glomeruli affected.

*Results: 198 biopsies with no glomerulitis, (g(0), had median dd-cfDNA = 0.31%, while 35 had g(1) median 1.1%, g(2) 1.8% or g(3) 1.27%. Significant differences were observed between normal and active g lesions, but not across spectrum of active g lesions. There were statistically significant differences between g(0) and g(1) [p=1.63e-05] and g(2) [p=4.12e-08]. Despite the sample-size (n=8), the putative trend discordance for the severe g(3) was significant with respect to g(0) [p=0.0183].

*Conclusions: Isolated glomerulitis has some correlation with dd-cfDNA which may enhance interpretation compared to Banff criteria alone. Active histological changes may not precisely correlate with graft injury and so considering higher plasma dd-cfDNA levels regardless of the degree of glomerulitis may be beneficial to interpretation.

To cite this abstract in AMA style:

Bu L, Anand S, Pai A, Bromberg JS, Gupta G, Moinuddin I, Alhamad T, Bowers V, Ghosh S, Tian W, Stites E. Plasma Donor-Derived Cell-Free DNA Levels Risk-Stratify Kidney Allograft Injury with Isolated Transplant Glomerulitis [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/plasma-donor-derived-cell-free-dna-levels-risk-stratify-kidney-allograft-injury-with-isolated-transplant-glomerulitis/. Accessed November 24, 2024.

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