Urinary exosomes: is there a future?

Tiny vesicles called ‘exosomes’, recently discovered in normal urine [1], provide a non-invasive means of acquiring unique information about the physiological or pathophysiological state of their renal cells of origin. Exosomes are delivered to the urine from all renal epithelial cell types. Consequently, analysis of urinary exosomes may provide a source of protein biomarkers for diseases involving glomerular podocytes, the various renal tubule segments or the transitional epithelium lining the urinary drainage tract [1]. Here, we discuss possible applications of urinary exosome analysis, as well as barriers to the development of practical clinical tools for exosome analysis. Exosomes originate as the internal vesicles of multivesicular bodies (MVBs) in cells (Figure 1). They were first described as products of circulating blood cells [2], such as erythrocytes and lymphocytes, and are probably formed by most cell types throughout the body. In the kidney, exosomes are released to the urine by fusion of the outer membrane of the MVBs with the apical plasma membrane (Figure 1). Proteomic analysis of urinary exosomes using tandem mass spectrometry approaches [1] revealed membrane proteins from each cell type facing the urinary space. In addition, the lumens of exosomes contain many cytosolic proteins that are entrained when the exosomes are formed in the MVBs. Thus, urinary exosomes can provide the investigator with a sampling of membrane and cytosolic proteins from each renal epithelial cell type. Through the use of liquid chromatography-tandem mass spectrometry (LC-MS/MS), more than a thousand proteins have been detected (Gonzales, Pisitkun and Knepper, unpublished data). In urine from normal subjects, urinary exosomes account for ∼3% of the total urinary protein [3]. Hence, when exosomes are isolated, their constituent proteins are enriched >30-fold, enhancing the detectability of rare proteins that may have diagnostic value.