Extracellular Vesicles: Cell-Derived Biomarkers of Glomerular and Tubular Injury.

Extracellular vesicles (EVs) are important mediators of intercellular communication. Since EVs are also released during pathological conditions, there has been considerable interest in their potential as sensitive biomarkers of cellular stress and/or injury. In the context of kidney disease, urinary EVs are promising indicators of glomerular and tubular damage. In the present review we discuss the role of urinary EVs in kidney health and disease. Our focus is to explore urinary large EVs (lEVs, often referred to as microparticles or microvesicles) as direct and noninvasive early biomarkers of renal injury. In this regard, studies have been demonstrating altered levels of urinary lEVs, especially podocyte-derived lEVs, preceding the decrease of renal function assessed by classical markers. In addition, we discuss the role of small EVs (sEVs, often referred to as exosomes) and their contents in kidney pathophysiology. Even though results concerning the production of sEVs during diseased conditions are varied, there has been a consensus on the importance of urinary sEV content assessment in kidney disease. These mediators, including EV-released miRNAs and mRNAs, are responsible for EV-mediated signaling in the regulation of renal cellular homeostasis, pathogenesis and regeneration. Finally, steps necessary for the validation of EVs as reliable markers will be discussed.