Remission of nephrotic syndrome diminishes urinary plasmin content and abolishes activation of ENaC

Mikkel René Andersen, Kristian B Buhl, Boye L Jensen, Per Svenningsen, Ulla G Friis, Bente Jespersen, Søren Rittig

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Abstrakt

Background: Urinary plasmin activates the epithelial Na + channel (ENaC) in vitro and may possibly be a mechanism of sodium retention in nephrotic syndrome (NS). This study used a paired design to test the hypothesis that remission of NS is associated with a decreased content of urinary plasmin and reduced ability of patients' urine to activate ENaC. Methods: Samples were collected during active NS and at stable remission from 20 patients with idiopathic NS, aged 9.1 ± 3.2 years. Plasminogen-plasmin concentration was measured with an enzyme-linked immunosorbent assay. Western immunoblotting for plasminogen-plasmin was performed in paired urine samples. The patch clamp technique was used to test the ability of urine to evoke an inward current on collecting duct cells and human lymphocytes. Results: The urinary plasminogen-plasmin/creatinine ratio was 226 [95 % confidence interval (CI) 130-503] μg/mmol in nephrotic urine versus 9.5 (95 % CI 8-12) μg/mmol at remission (p < 0.001). Western immunoblotting confirmed the presence of active plasmin in urine collected during active NS, while samples collected at remission were negative. Nephrotic urine generated an inward amiloride- and α 2-anti-plasmin- sensitive current, whereas the observed increase in current in urine collected at remission was significantly lower (201 ± 31 vs. 29 ± 10 %; p = 0.005). Conclusions: These findings support the hypothesis that aberrantly filtered plasminogen-plasmin may contribute to ENaC activation and mediate primary renal sodium retention during active childhood NS.

OriginalsprogEngelsk
TidsskriftPediatric Nephrology
Vol/bind28
Udgave nummer8
Sider (fra-til)1227-1234
Antal sider8
ISSN0931-041X
DOI
StatusUdgivet - 16. mar. 2013

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