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In animal models of nephrotic syndrome, the amiloride\u2010sensitive epithelial sodium channel ENaC is activated while more proximal renal Na<jats:sup>+<\/jats:sup> transporters are down\u2010regulated. With suppressed plasma aldosterone concentration and little change in ENaC abundance in nephrotic syndrome, the alternative modality of proteolytic activation of ENaC has been explored. Proteolysis leads to putative release of an inhibitory peptide from the extracellular domain of the \u03b3 ENaC subunit. This leads to full activation of the channel. Plasminogen has been demonstrated in urine from patients with nephrotic syndrome and pre\u2010eclampsia. Urine plasminogen correlates with urine albumin and is activated to plasmin within the urinary space by urokinase\u2010type plasminogen activator. This agrees with aberrant filtration across an injured glomerular barrier independent of the primary disease. Pure plasmin and urine samples containing plasmin activate inward current in single murine collecting duct cells. In this study, it is shown that human lymphocytes may be used to uncover the effect of urine plasmin on amiloride\u2010 and aprotinin\u2010sensitive inward currents. Data from hypertensive rat models show that protease inhibitors may attenuate blood pressure. Aberrant filtration of plasminogen and conversion within the urinary space to plasmin may activate \u03b3 ENaC proteolytically and contribute to inappropriate NaCl retention and oedema in acute proteinuric conditions and to hypertension in diseases with chronic microalbuminuria\/proteinuria.<\/jats:p>","DOI":"10.1111\/apha.12047","type":"journal-article","created":{"date-parts":[[2012,12,6]],"date-time":"2012-12-06T14:01:12Z","timestamp":1354802472000},"page":"536-545","source":"Crossref","is-referenced-by-count":51,"title":["Mechanisms of renal NaCl retention in proteinuric disease"],"prefix":"10.1111","volume":"207","author":[{"given":"P.","family":"Svenningsen","sequence":"first","affiliation":[{"name":"Cardiovascular and Renal Research Institute of Molecular Medicine University of Southern Denmark Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U. 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