D075 - Association of Allosure Plus with Histopathologic Diagnoses and Allograft Outcomes in Kidney Transplant Recipients

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Author Block: S. Shah¹, S. Voora¹, P. Hanson², W. Tian³, S. LeCorchick⁴, T. Maw¹, ¹University of Southern California Keck Hospital, Los Angeles, CA, ²CareDx, Venice, CA, ³CareDx, Brisbane, CA, ⁴Medical Affairs, CareDx, Brisbane, CA
*Purpose: AlloSure Plus® (AS+) is a multidimensional, automated rejection prediction tool for kidney transplant recipients (KTRs), integrating donor-derived cell-free DNA (dd-cfDNA, AlloSure®) with traditional clinical parameters: eGFR, graft dysfunction, prior rejection, and proteinuria. The relationship between AS+ scores and histopathologic diagnoses, as well as the prognostic relevance of abnormal AS+ values, remains undefined. This study compares AS+ across histologic diagnoses and examines its association with graft outcomes.
*Methods: KTRs (1/1/2017-12/31/2023) with biopsy, dd-cfDNA ≤30 days pre-biopsy, and all AS+ clinical inputs were included. Primary analysis compared median AS+ results across histologic diagnoses: acute cellular rejection (ACR), antibody-mediated/mixed rejection (AMR), borderline rejection (BR), and no rejection (NR, including ATI/ATN, glomerulopathy, and CNI toxicity) using non-parametric tests and AUROC. Kaplan-Meier analysis was used to compare outcomes.
*Results: Among 119 AS+ results, there were 17 ACR, 17 AMR, 25 BR, and 60 NR. Median AS+ was significantly higher in ACR (44%, IQR 36-67%) and AMR (48%, IQR 18-59%) versus no rejection (19%, IQR 10-27%) (p=0.0001 and p<0.0011, respectively) [Figure 1]. BR (23%, IQR 11-53%) was not different from no rejection (p=0.12) (Figure 1). The AUROC for AS+ to discriminate rejection was 0.79 (95% CI: 0.69-0.88). A 35% AS+ threshold (Youden's index) distinguished rejection with 87% specificity and 71% sensitivity (Figure 2). KTR with AS+ ≥35% trended toward worse composite outcomes of future rejection, graft loss, and death, likely nonsignificant due to small sample size [p=0.17, Figure 3]. A 12.5% threshold yielded a NPV of 92%. KTR with AS+ ≥12.5% had worse iBox estimated graft survival compared to <12.5% [Figure 4].
*Conclusions: This study establishes median AS+ values for no rejection and rejection subtypes in our transplant program, highlighting AS+’s utility in risk stratification. KTRs with abnormal AS+ scores trended toward worse composite outcomes and iBox scores. These reference values can help our providers interpret AS+ results and guide clinical decision-making.