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A Novel Approach to Non-Invasive Multimodality Testing with Allosure and Allomap Predicts Microvascular Inflammation with High Accuracy in Kidney Transplant Recipients

S. Parajuli, F. Aziz, N. Garg, S. E. Panzer, K. Van Hyfte, K. Degner, S. Reese, L. Ptak, N. Wilson, A. Djamali

University of Wisconsin, Madison, WI

Meeting: 2022 American Transplant Congress

Abstract number: 1535

Keywords: Biopsy, Genomic markers, HLA antibodies, Rejection

Topic: Basic Science » Basic Clinical Science » 17 - Biomarkers: Clinical Outcomes

Session Information

Session Name: Biomarkers: Clinical Outcomes

Session Type: Poster Abstract

Date: Tuesday, June 7, 2022

Session Time: 7:00pm-8:00pm

 Presentation Time: 7:00pm-8:00pm

Location: Hynes Halls C & D

*Purpose: The most prominent histologic lesion in antibody-mediated rejection (ABMR) is microvascular inflammation (MVI); however, its recognition and scoring can be challenging and poorly reproducible between pathologists. The clinical and molecular significance of different Banff MVI scores continues to involve and is especially important for C4d negative biopsies. We sought to determine the characteristics of AlloSure (AS) donor-derived cell-free DNA (dd-cfDNA) and AlloMap Kidney (AMK) peripheral blood-based gene expression (CareDx, Brisbane, CA) to better characterize MVI.

*Methods: Kidney transplant recipients with historic or current DSA from the All-MAP study (NCT04057742) were prospectively examined. For this study, we specifically examined the diagnostic characteristics of a composite AS + AMK score for a diagnosis of MVI >1.

*Results: A total of 27 kidney biopsies in 26 KTRs we enrolled. The mean age at transplant was 54.1 ± 13.2 years, 37% were female and 30% were non-white. The mean MFI against class I was 543 ± 1497, and MFI against class II antigens around the time of biopsy was 16374 ± 14337. Logistic regression was used to develop a weighted composite score in this cohort to distinguish patients with MVI 0 and 1 against those with 2 and above, MVI = -9.1444 + 2.3122 * AlloSure + 0.5462 * AlloMap. Median scores for AS, AMK, and composite scores were 0.76 , 11.7 and -0.3616 , respectively. The composite score had very high accuracy in identifying patients with MVI> 1 with an AUC of 0.87. The optimum threshold for this score was -0.3981 with a Sensitivity of 0.92, Specificity 0.73, PPV 0.73, and NPV: 0.92. An elevated score of 0.82 yielded a sensitivity of 0.58, NPV of 0.75, specificity, and PPV of 100%. A low score of -3.17 had sensitivity and NPV of 100%, specificity 27%, and PPV 52%. Performance characteristic of this score for MVI>1 at different thresholds is highlighted in Table 1.

*Conclusions: Multimodality testing with AS, and AMK could be used as a screening tool to rule out MVI in kidney transplant recipients if validated in larger data sets.

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To cite this abstract in AMA style:

Parajuli S, Aziz F, Garg N, Panzer SE, Hyfte KVan, Degner K, Reese S, Ptak L, Wilson N, Djamali A. A Novel Approach to Non-Invasive Multimodality Testing with Allosure and Allomap Predicts Microvascular Inflammation with High Accuracy in Kidney Transplant Recipients [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/a-novel-approach-to-non-invasive-multimodality-testing-with-allosure-and-allomap-predicts-microvascular-inflammation-with-high-accuracy-in-kidney-transplant-recipients/. Accessed May 25, 2025.

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