Cardiorenal syndrome (CRS) comprises five clinically distinct patterns of acute, chronic, or systemic heart-kidney interaction. Mitochondrial dysfunction is shared by cardiac and renal injury, but the cardiorenal setting is distinguished by the possibility that mitochondrial stress arising in one organ is externalized and transmitted to the other. Extracellular vesicles (EVs) are established mediators of intercellular communication, and EVs carrying mitochondrial DNA, proteins, lipids, RNA, or structurally preserved mitochondrial material-collectively referred to here as mitochondrial extracellular vesicles (mitoEVs)-may connect mitochondrial quality control with systemic signaling. Direct CRS-specific evidence, however, remains limited: patient-derived studies support pathogenic effects of total circulating EVs, whereas most mitoEV-specific mechanisms are inferred from related cardiovascular, renal, inflammatory, cancer, or regenerative models. Accordingly, this review presents an evidence-graded conceptual framework rather than a definitive mechanistic summary. We define and classify mitoEVs, outline methodological requirements for their isolation, same-particle identification, cargo-topology analysis, quantification, and functional validation, and map the available evidence across the five CRS subtypes. We further propose the mitoEV-mitophagy-inflammation axis as a working hypothesis in which impaired mitochondrial quality control may favor vesicular export, inflammatory activation in recipient cells, and secondary mitochondrial dysfunction. Finally, we evaluate the biomarker and therapeutic potential of mitoEVs while emphasizing the need for subtype-specific clinical validation, standardized analytical workflows, source-resolved studies, and rigorous distinction between pathological and reparative vesicle populations.
