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Induction of nephrotic syndrome in mice by retrobulbar injection of doxorubicin and prevention of volume retention by sustained release aprotinin.

J. Vis. Exp.:e57642 (2018)
Open Access Green as soon as Postprint is submitted to ZB.
Nephrotic syndrome is the most extreme manifestation of proteinuric kidney disease and characterized by heavy proteinuria, hypoalbuminemia, and edema due to sodium retention and hyperlipidemia. To study the pathophysiology of this syndrome, rodent models have been developed based on the injection of toxic substances such as doxorubicin causing podocyte damage. In mice, only few strains are susceptible to this model. In wildtype 129S1/SvImJ mice, the administration of doxorubicin by rapid intravenous injection to the retrobulbar sinus induces experimental nephrotic syndrome that features all the symptoms of human disease including sodium retention and edema. After the onset of proteinuria, mice exhibit increased urinary serine protease activity that leads to the activation of the epithelial sodium channel (ENaC) and sodium retention. Pharmacological inhibition of urinary serine proteases by the treatment with sustained release aprotinin abrogates ENaC activation and prevents sodium retention. This model is ideal to study the pathophysiology of proteasuria, i.e., the excretion of active serine proteases that cause ENaC activation by the proteolysis of its gamma-subunit. This can be regarded as the primary mechanism of ENaC activation and sodium retention in proteinuric kidney disease.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Medicine ; Issue 135 ; Experimental Nephrotic Syndrome ; Doxorubicin ; Mice ; Retrobulbar ; Aprotinin ; Proteasuria; Epithelial Sodium-channel; Adriamycin Nephropathy; Model; Glomerulosclerosis; Mouse
ISSN (print) / ISBN 1940-087X
e-ISSN 1940-087X
Quellenangaben Volume: , Issue: 135, Pages: , Article Number: e57642 Supplement: ,
Publisher JoVE
Publishing Place 1 Alewife Center, Ste 200, Cambridge, Ma 02140 Usa
Reviewing status Peer reviewed