Kidney-heart crosstalk: the extracellular vesicles connection

Abstract

Chronic kidney disease (CKD) is a major public health concern, closely linked to an increased risk of cardiovascular disease (CVD), which remains the leading cause of morbidity and mortality in this population. While traditional risk factors such as hypertension and diabetes are prevalent in CKD, disease-specific mechanisms-including chronic inflammation, oxidative stress, mineral disturbances and the accumulation of uraemic toxins-further amplify cardiovascular vulnerability. In CKD, both the abundance and molecular cargo of circulating extracellular vesicles (EVs) are altered, reflecting the underlying metabolic and inflammatory milieu. These EVs propagate endothelial dysfunction, vascular calcification, inflammation, thrombosis and cardiac remodelling by transferring bioactive molecules such as proteins and microRNAs to target cells. Emerging evidence suggests that EVs not only serve as biomarkers for early detection and risk stratification of CVD in CKD but may also represent novel therapeutic targets. Preclinical studies demonstrate the potential of stem cell-derived and engineered EVs to promote cardiac repair and modulate pathological signalling. However, translation into clinical practice requires rigorous standardization, safety validation and well-designed human trials. This review synthesizes current knowledge on the mechanisms by which EVs bridge renal dysfunction and cardiovascular pathology, discusses their utility as biomarkers and outlines a research agenda for harnessing their therapeutic potential in CKD-associated CVD.