Renal extracellular vesicles: from physiology to clinical application

Abstract

Urinary extracellular vesicles (uEVs) are released from all regions of the kidney's nephron and from other cells that line the urinary tract. Extracellular vesicles retain proteomic and transcriptomic markers specific to their cell of origin and so represent a potential reservoir for kidney disease biomarker discovery. Exosomes, a subtype of uEVs, are distinguished from other vesicles by features related to their biogenesis within cells: mature multi-vesicular bodies fuse with the cellular membrane to liberate exosomes into the extracellular space. uEVs represent a novel cell signalling mechanism because they can be shuttled to a recipient cell and, through a number of proposed mechanisms, affect the recipient cell's proteome and function. Here we review the current evidence for uEV signalling along the nephron, their role in health and disease of the kidney, and their potential for clinical translation as biomarkers and therapeutics.

HMGB1+ microparticles present in urine are hallmarks of nephritis in patients with systemic lupus erythematosus

“…This result it is not surprising, considering that significant leukocyte infiltration occurs in the renal tissue of these patients . Although circulating MPs do not cross to glomeruli under normal physiological conditions , it is possible that endothelial damage caused by inflammatory states might allow glomerular infiltration of MPs. Therefore, the MPs detected in urine could be a mixture of those in circulation and those generated in the kidney during renal inflammation.…”

“…A variety of evidence indicates that extracellular vesicles participate in the developmental processes of the normal kidney . In addition, extracellular vesicles in renal tissue are also involved in pathological conditions, including acute kidney injuries and chronic kidney diseases such as polycystic kidney disease, renal fibrosis, ischemia/reperfusion injury, and renal carcinoma . As a result, recent efforts have focused on the study of extracellular vesicles in urine, including MPs and exosomes, since these structures can be considered a remote biopsy that gives important clues about organ status and cellular damage .…”

Therapeutic application of extracellular vesicles in kidney disease: promises and challenges

“…EVs encompass a vast heterogeneous population of membrane‐bound vesicles, which are classified as exosomes, microvesicles and apoptotic bodies based on their size and biogenesis in most reviews and have been extensively discussed elsewhere . EVs biogenesis and its content are not only determined by their cellular source but are also sensitive to cellular status and environmental changes.…”

Roles for Exosome in Various Kidney Diseases and Disorders

“…Exosome can be found in several biological fluids, e.g., blood, seminal fluid, cerebrospinal fluid, synovial fluid, breast milk, saliva, bile, ascitic fluid, amniotic fluid, pleural fluid, and urine (Lin et al, 2015). For the renal system, recent studies have investigated the compositions of urinary exosomes secreted from different segments of the nephron and their relevance to the renal physiology and pathophysiology of kidney diseases (Morrison et al, 2016;Pomatto et al, 2017;Stahl et al, 2019). In addition, roles for exosomes derived from serum/plasma/blood, renal tubular cells, renal tissues, glomerular endothelial cells, mesenchymal stem cells (MSCs), urinary stem cells, cancer cells, and macrophages related to kidney diseases have been also examined.…”