Acute regulated expression of pendrin in human urinary exosomes.

It is well known that pendrin, an apical Cl/HCOexchanger in type B intercalated cells, is modulated by chronic acid-base disturbances and electrolyte intake. To study this adaptation further at the acute level, we analyzed urinary exosomes from individuals subjected to oral acute acid, alkali, and NaCl loading. Acute oral NHCl loading (n = 8) elicited systemic acidemia with a drop in urinary pH and an increase in urinary NH excretion. Nadir urinary pH was achieved 5 h after NHCl loading. Exosomal pendrin abundance was dramatically decreased at 3 h after acid loading. In contrast, after acute equimolar oral NaHCO loading (n = 8), urinary and venous blood pH rose rapidly with a significant attenuation of urinary NH excretion. Alkali loading caused rapid upregulation of exosomal pendrin abundance at 1 h and normalized within 3 h of treatment. Equimolar NaCl loading (n = 6) did not alter urinary or venous blood pH or urinary NH excretion. However, pendrin abundance in urinary exosomes was significantly reduced at 2 h of NaCl ingestion with lowest levels observed at 4 h after treatment. In patients with inherited distal renal tubular acidosis (dRTA), pendrin abundance in urinary exosomes was greatly reduced and did not change upon oral NHCl loading. In summary, pendrin can be detected and quantified in human urinary exosomes by immunoblotting. Acid, alkali, and NaCl loadings cause acute changes in pendrin abundance in urinary exosomes within a few hours. Our data suggest that exosomal pendrin is a promising urinary biomarker for acute acid-base and volume status changes in humans.