Microparticles at the crossroads of the gut-kidney axis: Mechanistic drivers and therapeutic horizons in hemodialysis.

Chronic kidney disease (CKD) and end-stage kidney disease (ESKD) pose significant global health challenges, with hemodialysis serving as a vital treatment for ESKD patients. Despite its life-sustaining role, hemodialysis is associated with elevated cardiovascular morbidity and mortality, driven in part by the accumulation of uremic toxins. Recent research underscores the gut-kidney axis as a pivotal contributor to CKD progression and its complications, with gut microbiota dysbiosis amplifying uremic toxin production. Microparticles (MPs)-small extracellular vesicles released from cells-have emerged as key mediators in intercellular communication, inflammation, and vascular dysfunction. This review examines the role of MPs in the gut-kidney axis, with a focus on their contribution to uremic toxicity and clinical outcomes in hemodialysis patients. We explore how MPs, originating from endothelial cells, platelets, and gut microbiota, transport bioactive molecules, intensify inflammation, and impair endothelial function, thereby heightening cardiovascular risk. Furthermore, we assess their potential as biomarkers of disease severity and as novel therapeutic targets. By integrating current evidence, this review elucidates the intricate interplay between MPs, the gut-kidney axis, and uremic toxicity, offering fresh insights into improving outcomes for hemodialysis patients.