title: Proteinuric diseases with sodium retention: Is plasmin the link?
abstract: 1. Sodium retention in disease states characterized by proteinuria, such as nephrotic syndrome, pre-eclampsia and diabetic nephropathy, occurs through poorly understood mechanism(s). 2. In nephrotic syndrome, data from experimental and clinical studies show that the sodium retention originates in the renal cortical collecting duct and involves hyperactivity of the epithelial sodium channel (ENaC). 3. The stimulus for the increased ENaC activity does not appear to involve any of the classical sodium retaining mechanisms, such as the renin-angiotensin-aldosterone system, arginine vasopressin or the sympathetic nervous system. 4. Proteolytic processing of the extracellular domain of γENaC subunit has been shown to stimulate ENaC activity. 5. The serine protease plasmin was recently identified as an ENaC-activating protease in urine from human nephrotic patients and from the puromycin aminonucleoside (PAN) rat model of nephrotic syndrome. 6. This finding suggests that a defective glomerular filtration barrier allows filtration into the tubular fluid of substances that activate ENaC and enhance sodium reabsorption. This concept might be expanded to other disease states, such as pre-eclampsia and diabetic nephropathy, which are also characterized by proteinuria and sodium retention. 7. In this review, we will examine the evidence for a role of urinary serine protease activity in the development of sodium and water retention in diseases characterised by proteinuria with a focus on nephrotic syndrome.
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark. psvenningsen@health.sdu.dk
authors.forename: Per
authors.initials: P
authors.lastname: Svenningsen
authors.forename: Ole
authors.initials: O
authors.lastname: Skøtt
authors.forename: Boye L
authors.initials: BL
authors.lastname: Jensen
mesh_terms: D000818:Animals; D062708:Epithelial Sodium Channel Agonists; D053503:Epithelial Sodium Channels / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism* / Q000652:urine; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D007684:Kidney Tubules / Q000378:metabolism / Q000503:physiopathology; D009318:Natriuresis; D009404:Nephrotic Syndrome / Q000503:physiopathology; D010958:Plasminogen / Q000378:metabolism; D011507:Proteinuria / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology / Q000652:urine; D017673:Sodium Chloride, Dietary / Q000009:adverse effects; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D014883:Water-Electrolyte Imbalance / Q000209:etiology*
chemical_list: D062708:Epithelial Sodium Channel Agonists; D053503:Epithelial Sodium Channels; D017673:Sodium Chloride, Dietary; D010958:Plasminogen; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator