Extracellular vesicles mediate immune regulation in acute kidney injury

Acute kidney injury (AKI) arises from diverse insults that trigger distinct immune responses, and an integrative framework for intercellular communication is now emerging. Extracellular vesicles (EVs), membrane-enclosed particles carrying proteins, microRNAs, lipids, and metabolites, mediate crosstalk between renal parenchymal cells and immune effectors to shape inflammation and repair. This review examines three dimensions of EV biology in AKI. This review examines three dimensions of EV biology in AKI, applying the term 'EV' throughout in accordance with MISEV2023 guidance unless the cited primary study has experimentally established subtype origin. First, we outline the molecular basis of EV-mediated immune signaling by contrasting vesicular communication with soluble cytokine and cell-contact pathways, highlighting cargo stability, tissue tropism, and multi-signal integration as distinguishing features. Second, we describe how EV composition shifts after injury: tubular epithelial cells, podocytes, and endothelial vesicles become enriched in damage-associated patterns and pro-inflammatory microRNAs, whereas immune cell-derived EVs propagate or resolve inflammation depending on polarization and disease phase. Third, we compare vesicular signaling across four AKI etiologies (allograft rejection, sepsis, nephrotoxicity, and ischemia-reperfusion), noting that EV cargo, cellular origin, and immune targets differ markedly by insult type and evolve through early, peak, and reparative phases. Advances in single-vesicle proteomics, intravital imaging, and kidney organoid systems now enable functional dissection of EV heterogeneity at unprecedented resolution. Key gaps remain: the limited mechanistic definition of dendritic cell- and T cell-derived EVs in non-transplant settings, the underdeveloped vesicular framework for renal ischemia-reperfusion, and the absence of standardized clinical assays. Addressing these limitations is essential for translating mechanistic insights into etiology-stratified diagnostics and stage-matched immunomodulatory interventions.