#3202 Biopsy-based transcript diagnostics improves prognostication along the AMR continuum

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Abstract Background and Aims Clinical utility of biopsy-based transcript diagnostics with respect to risk stratification and prognostication for graft outcome used in addition to histology along the AMR continuum of Banff 2022 has not been investigated. Method We examined 297 kidney allograft biopsies by histology and the Molecular Microscope Diagnostic System (MMDx) from 2021 to 2023. Histologic findings were grouped into probable AMR (n = 52), DSA-negative C4d-negative MVI (n = 42), AMR (n = 71), and no AMR (n = 132). Groups were further divided into those with (n = 86) and without molecular signs of AMR (n = 211). Outcome was assessed using a combined endpoint of allograft loss, eGFR < 15 ml/min and eGFR decline of >30%. Results We followed kidney allograft biopsy cases for a median of 27 months (IQR 18; 38). Molecular AMR was found in 56% of AMR, 69% of DSA-negative MVI, 13% of probable AMR, and 6% with no AMR. At 1, 3, and 5 years after biopsy, molecular AMR cases had higher rates of the combined endpoint than no molecular AMR (25% vs. 4%, 28% vs. 8%, 54% vs. 11%; P = 0.0003). This difference was reproducible in all histologic groups. Rejection archetype R3 (P < 0.0001), R5 (P = 0.048) and R6 (P < 0.0001) showed significantly higher rates of combined endpoint than no molecular AMR. Creatinine (P = 0.003), proteinuria (P = 0.019), R3 (P = 0.001) and R6 archetype score (P = 0.005) and IFTA classifier score (P = 0.052) remained independent predictors of outcome in a multivariate analysis. Conclusion Molecular AMR is associated with higher rates of kidney allograft loss and eGFR decline along the AMR continuum defined by Banff 2022.

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