Urinary Extracellular Vesicles as Source of Biomarkers in Kidney Diseases

Abstract

Most cells physiologically release vesicles as way of intercellular communication. The so-called Extracellular Vesicles (EVs) include exosomes, ectosomes, and apoptotic bodies, which basically differ in their composition and subcellular origin. Specifically, EVs found in urine reflect the state of the urinary system, from podocytes to renal-tubular cells, thus making them an excellent source of samples for the study of kidney physiology and pathology. Several groups have focused on defining biomarkers of kidney-related disorders, from graft rejection to metabolic syndromes. So far, the lack of a standard protocol for EVs isolation precludes the possibility of a proper comparison among the different biomarkers proposed in the literature, stressing the need for validation of these biomarkers not only in larger cohorts of patients but also considering the different methods for EVs isolation. In this review, we aim to gather the current knowledge about EVs-related biomarkers in kidney diseases, with a special emphasis in the methods used to date for EVs enrichment, and discussing the need for more specific protocols of EV isolation in clinical practice.

The human urinary exosome as a potential metabolic effector cargo

“…Urine is a waste fluid variably composed of proteins, salts, urea and metabolites, ideal for biomarker determination [18] as it can be easily obtained in adequate amounts, in a non-invasive or minimally invasive way. Normal urine contains a small but constant amount of proteins, derived from each nephron segment, but also from blood circulation.…”

Prostasomes as a source of diagnostic biomarkers for prostate cancer

“…One advantage of collecting EVs from urine, as compared with blood, is that such isolates are more enriched in prostasomes relative to other constituents, although tissues within the urogenital system other than the prostate, including the kidney (74) and bladder (75), also contribute EVs to urine. Moreover, urine also contains intact PCa cells and PCa cell-derived apoptotic bodies (74). Cells and most apoptotic bodies are considerably larger than prostasomes and can thus be easily separated from prostasomes by differential centrifugation.…”

Microparticles in kidney diseases: focus on kidney transplantation

“…Interestingly, different quantities of NGAL were detected between deceased and living donors. Thus, various studies suggest that NGAL could be a biomarker of damage and delayed graft function [70,71].…”