Urinary proteomics: role of putative markers of Epithelial Sodium Channel (ENac) activation

Urine proteomic is becoming an useful approach to discover potential biomarkers of disease. We investigated arterial hypertension and specifically primary aldosteronism (PA), analyzing urine and urinary exosomes in healthy subjects and hypertensive patients. Primary aldosteronism (PA) is the most common cause of secondary hypertension caused by an aldosterone excess with consistent sodium retention and volume expansion mediated by the renal epithelial sodium channel (ENaC) activation. Despite the high prevalence of the disease, the physiological regulation of ENaC activation is not yet fully elucidated, and the PA diagnostic work-up still lacks optimal accuracy. Prostasin, a GPI-anchored serine protease, activates ENaC leading to Na+ reabsorption; prostasin is released in extracellular fluids, including urine. Previous data have suggested a direct association between urinary prostasin and the activation of an aldosterone-driven pathway, but a quantitative association has never been demonstrated in normotensive subjects. We analyzed urine of healthy subjects with a quantitative method (ELISA assay) and we found prostasin in both the genders without differences; we described a direct correlation between prostasin and natriuresis and between prostasin and ARR (aldosterone to renin ratio, the screening test used for primary aldosteronism diagnosis). Moreover prostasin seemed to be modulated, like ARR, by estro-progestinic therapy in normotensive young women. Prostasin presented a diurnal variation pattern similarly to ARR and ADH. In hypertensive patients prostasin was higher in those affected by PA compared with those with essential hypertension (EH). In conclusion urinary prostasin seems to grossly reflect the extent of ENaC activation in vivo.