Diseases associated with proteinuria are linked to ENaC activation

We have recently identified plasmin in urine from humans and rats with nephrotic syndrome as an activator of ENaC channels (1). We hypothesized that the ability of plasmin to stimulate ENaC activity is common for other clinical conditions associated with proteinuria, and we investigated this hypothesis in a collecting duct cell line (M1 cells) by whole‐cell patch clamp. Urine samples from healthy pregnant women, preeclamptic women and pregnant women with diabetes type 1 were tested. When M1 cells were superfused with urine from healthy pregnant women, no significant changes in ENaC current were observed (12.5 ± 19.5 % (P>0.05)). Urine from diabetic pregnant woman significantly increased ENaC currents (123.5% ± 33.3%, P<0.05), and similarly, urine from preeclamptic woman increased ENaC currents (190.3% ± 49.4%; P<0.01). This increase in ENaC current was abolished in the presence of amiloride (2 μM), ‐ a concentration specific for ENaC inhibition. Taken together, these data support our hypothesis that the ability of plasmin to stimulate ENaC activity is not unique for nephrotic syndrome but is associated with overt proteinuria.