Urinary extracellular vesicles: does cargo reflect tissue?

To review recent developments in urinary extracellular vesicles (uEVs) to study kidney physiology and disease.Proteomic analysis in rats showed significant correlations between kidney and uEV protein abundances. Consistent with uEV biogenesis, these correlations were stronger for membrane-associated proteins than for e.g. soluble kinases or E3 ubiquitin ligases. When challenged with a high potassium diet, the physiologically predicted protein changes occurred both in kidney and uEVs, suggesting that analysis of uEVs might be utilized as a proxy or even replacement for tissue analysis. Although kidney-uEV correlations are more difficult to obtain in humans, analysis of uEV cargo from patients with inherited tubulopathies or with primary aldosteronism were also consistent with the predicted changes at the tissue level. The kidney appears to be the main source of uEVs, with a recent study showing that nephron mass determines uEV excretion rate. Therefore, a measure of nephron mass should be included for between-subject comparisons.The overall good correlation between kidney and uEV protein abundances renders uEVs an attractive noninvasive source of biomarkers for studying kidney physiology or disease. However, differences in per-protein kidney-uEV correlations and per-person uEV excretion rates should be considered in uEV biomarker studies.