Extracellular Vesicles in Renal Diseases: More than Novel Biomarkers?

Extracellular vesicles from the urine and circulation have gained significant interest as potential diagnostic biomarkers in renal diseases. Urinary extracellular vesicles contain proteins from all sections of the nephron, whereas most studied circulating extracellular vesicles are derived from platelets, immune cells, and the endothelium. In addition to their diagnostic role as markers of kidney and vascular damage, extracellular vesicles may have functional significance in renal health and disease by facilitating communication between cells and protecting against kidney injury and bacterial infection in the urinary tract. However, the current understanding of extracellular vesicles has derived mostly from studies with very small numbers of patients or in vitro data. Moreover, accurate assessment of these vesicles remains a challenge, in part because of a lack of consensus in the methodologies to measure extracellular vesicles and the inability of most techniques to capture the entire size range of these vesicles. However, newer techniques and standardized protocols to improve the detection of extracellular vesicles are in development. A clearer understanding of the composition and biology of extracellular vesicles will provide insights into their pathophysiologic, diagnostic, and therapeutic roles.

Origin of EVs in renal diseases. Proteomic analysis has identified uEVs, including exosomes from glomerular, tubular, prostate, and bladder cells.

Here, is shown a schematic drawing of the glomerulus and kidney tubule. Several markers of podocyte damage have been identified in uEVs, including podocalyxin, podoplanin, and WT-1. A protective role of EVs derived from MSCs has been described in models of kidney damage. It is suggested that these EVs from MSCs are involved in transfer of mRNA, miRNA, and proteins and reprogramming of their phenotypes. Solute and water transporters have been identified on uEVs: sodium potassium chloride cotransporter (NaKCl) from the thick ascending limb, sodium chloride cotransporter (NCC) from the distal tubule, and AQP-2 deriving from the collecting duct.