EV-idence uncovered: kidney-on-chip study links circulating EVs of cardiorenal syndrome to renal pathology.

The intertwined nature of cardiac and renal failure, where dysfunction in one organ predicts a poor outcome in the other, has long driven the interest in uncovering the exact molecular links between the two. Elucidating the mechanisms driving Cardiorenal Syndrome (CRS) will enable the development of targeted therapies that disrupt this detrimental cycle, potentially improving outcomes for patients. A recent study by Chatterjee et al. (JCI insight 2023) demonstrated the feasibility of utilizing a humanized microfluidic kidney-on-chip model to elucidate the role of circulating extracellular vesicles (EVs) in the development of CRS (type 1 and type 2) in heart failure (HF) patients. The study also identified and validated EV miRNAs that correlated with kidney function by targeting several genes involved in kidney damage pathways, including transforming growth factor- β (TGF-β) signaling. These findings suggest that plasma EVs from CRS patients induce harmful responses in renal cells by regulating key pathways, highlighting their role in both type 1 and type 2 CRS.