Microvascular inflammation in the kidney transplant, beyond acute antibody-mediated rejection

Purpose of review Microvascular inflammation (MVI) is a central feature of allograft rejection, traditionally associated with antibody-mediated rejection (AMR), but its mechanisms and clinical impact extend beyond this framework. This review highlights recent updates in the Banff classification, insights into the mechanisms underlying MVI, and how these developments may refine diagnostic approaches and guide the development of therapeutic strategies. Recent findings The spectrum of MVI has been refined, with DSA-negative C4d-negative MVI and probable AMR now recognized as distinct entities associated with adverse graft outcomes. Mechanistic studies highlight the complementary roles of non-HLA antibodies, NK-cell-driven alloreactivity, and T-cell mediated injury. Molecular diagnostics have advanced our understanding of rejection phenotypes, while donor-derived cell-free DNA has emerged as the most robust and noninvasive biomarker of active microvascular injury. Novel therapies, particularly CD38-directed treatments such as felzartamab, have shown promising results in AMR but their efficacy across all MVI phenotypes remains to be established. Summary MVI represents a heterogeneous spectrum of alloimmune injuries that extends beyond the traditional AMR framework. Combining histology with emerging artificial intelligence tools, molecular diagnostics, and noninvasive biomarkers, will offer a more integrated approach to diagnosis, risk stratification, and development of novel therapies.