Abstract / Summary
Abstract Accurate diagnosis of kidney allograft pathology remains challenging, particularly in borderline biopsies and non-classical antibody-mediated rejection (ABMR), including isolated microvascular inflammation (iMVI). We retrospectively analyzed 219 consecutive kidney allograft biopsies (2019–2024) evaluated by Banff-based histology and parallel Molecular Microscope Diagnostic System (MMDx) testing. Histology and MMDx were concordant in 186/219 biopsies (84.9%). In 20/219 (9.1%), predominantly borderline/equivocal cases, MMDx was pivotal for the final clinicopathological diagnosis. Rejection was identified by both modalities in 45/219 (20.5%), with phenotype agreement in 37/45 (82.2%); rejection versus non-rejection discordance occurred in 17/219 (7.8%). Three-month changes in eGFR and proteinuria did not differ across histology/MMDx rejection concordance groups (p=0.786 and p=0.543), and graft failure up to 12 months post diagnosis was infrequent (p=0.324). Molecular ABMR-related signatures were detected in 12/16 (75.0%) C4d-negative histological ABMR/mixed and in 14/19 (73.7%) DSA-negative iMVI/mixed rejection biopsies. In Banff-relevant strata, molecular rejection was present in 9/12 (75.0%) iMVI (DSA−/C4d−) and 5/6 (83.3%) probable ABMR (DSA+/C4d−). Of 56/219 biopsies (25.6%) deemed histologically limited, MMDx yielded reportable results in all inadequate samples. Overall, integrating MMDx improved diagnostic confidence and refined rejection phenotyping in real-world practice.