Poroelastic modeling reveals the cooperation between two mechanisms for albuminuria

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dc.contributor.authorXu, Zelaien
dc.contributor.authorYue, Pengtaoen
dc.contributor.authorFeng, James J.en
dc.date.accessioned2022-12-22T12:56:35Zen
dc.date.available2022-12-22T12:56:35Zen
dc.date.issued2022-11-05en
dc.date.updated2022-12-21T21:27:59Zen
dc.description.abstractAlbuminuria occurs when albumin leaks abnormally into the urine. Its mechanism remains unclear. A gel-compression hypothesis attributes the glomerular barrier to compression of the glomerular basement membrane (GBM) as a gel layer. Loss of podocyte foot processes would allow the gel layer to expand circumferentially, enlarge its pores and leak albumin into the urine. To test this hypothesis, we develop a poroelastic model of the GBM. It predicts GBM compression in healthy glomerulus and GBM expansion in the diseased state, essentially confirming the hypothesis. However, by itself, the gel compression and expansion mechanism fails to account for two features of albuminuria: the reduction in filtration flux and the thickening of the GBM. A second mechanism, the constriction of flow area at the slit diaphragm downstream of the GBM, must be included. The cooperation between the two mechanisms produces the amount of increase in GBM porosity expected in vivo in a mutant mouse model, and also captures the two in vivo features of reduced filtration flux and increased GBM thickness. Finally, the model supports the idea that in the healthy glomerulus, gel compression helps maintain a roughly constant filtration flux under varying filtration pressure.en
dc.description.versionAccepted versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.issn1742-5662en
dc.identifier.orcidYue, Pengtao [0000-0001-8343-846X]en
dc.identifier.urihttp://hdl.handle.net/10919/112976en
dc.language.isoenen
dc.publisherThe Royal Societyen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.titlePoroelastic modeling reveals the cooperation between two mechanisms for albuminuriaen
dc.title.serialJournal of the Royal Society Interfaceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dcterms.dateAccepted2022-06-12en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/Mathematicsen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen

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