Urinary extracellular vesicles and tubular transport.

Tubular transport is a key function of the kidney to maintain electrolyte and acid-base homeostasis. Urinary extracellular vesicles (uEVs) harbor water, electrolyte, and acid-base transporters expressed at the apical plasma membrane of tubular epithelial cells. Within the uEV proteome, the correlations between kidney and uEV protein abundances are strongest for tubular transporters. Therefore, uEVs offer a non-invasive approach to probe tubular transport in health and disease. Here, we will review how kidney tubular physiology is reflected in uEVs and, conversely, how uEVs may modify tubular transport. Clinically, uEV tubular transporter profiling has been applied to rare diseases such as inherited tubulopathies, but also to more common conditions such as hypertension and kidney disease. Although uEVs hold the promise to advance the diagnosis of kidney disease to the molecular level, several biological and technical complexities still need to be addressed. The future will tell if uEV analysis will mainly be a powerful tool to study tubular physiology in humans or if it will move forward to become a diagnostic bedside test.