In:
Journal of The Royal Society Interface, The Royal Society, Vol. 20, No. 198 ( 2023-01)
Abstract:
Albuminuria 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 may help maintain a roughly constant filtration flux under varying filtration pressure.
Type of Medium:
Online Resource
ISSN:
1742-5662
DOI:
10.1098/rsif.2022.0634
Language:
English
Publisher:
The Royal Society
Publication Date:
2023
detail.hit.zdb_id:
2156283-0
