Extracellular Vesicles as Mediators of Endothelial and Tubular Injury in Cardiac Surgery-Associated Acute Kidney Injury

Cardiac surgery represents a cornerstone of modern cardiovascular medicine, yet it is in-trinsically linked to significant systemic stress responses that can compromise remote or-gan function. Among postoperative complications, cardiac surgery-associated acute kid-ney injury (CSA-AKI) remains a significant clinical challenge characterized by high mor-bidity and complex pathophysiology. While hemodynamic instability and ischemia–reperfusion injury are established risk factors, renal dysfunction frequently persists de-spite optimal perfusion. This observation suggests the involvement of potent circulating mediators in cellular injury. Extracellular vesicles (EVs) are essential for intercellular com-munication and serve as central hubs for transporting bioactive lipids, proteins, and ge-netic material. Accumulating evidence indicates that the mechanical and oxidative stress inherent to cardiopulmonary bypass triggers substantial release of EVs from platelets, erythrocytes, and injured vascular tissues. These vesicles may function as vectors that traf-fic oxidized mitochondrial components and pro-inflammatory cargo to the renal paren-chyma. This signaling cascade appears to disrupt renal homeostasis through a proposed “dual-hit” mechanism involving the induction of endothelial dysfunction and endothe-lial-to-mesenchymal transition (EndMT), followed by tubular epithelial injury via mito-chondrial fragmentation, redox imbalance, and downregulation of anti-aging factors. The complexity of these EV-mediated interactions may contribute to an incomplete under-standing of why specific patient phenotypes fail to recover. This narrative review exam-ines the mechanisms of surgery-induced EV biogenesis, the molecular pathogenesis of endothelial and tubular damage, and the role of intercellular crosstalk. Additionally, we discuss future perspectives on targeting the “EV vector” through therapeutic apheresis and mitochondrial pharmacotherapy to potentially improve clinical outcomes in high-risk surgical patients.