Poroelastic modelling reveals the cooperation between two mechanisms for albuminuria
Poroelastic modelling reveals the cooperation between two mechanisms for albuminuria
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DOI：
10.1098/rsif.2022.0634
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发表时间：
2023-01
影响因子：
3.9
通讯作者：
Zelai Xu;P. Yue;James J. Feng
中科院分区：
文献类型：
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作者：
Zelai Xu;P. Yue;James J. Feng
当白蛋白异常渗漏到尿液中时，就会发生白蛋白尿。其机制尚不清楚。凝胶压缩假说将肾小球屏障归因于肾小球基底膜（GBM）作为凝胶层的压缩。足细胞足突的缺失将使凝胶层周向扩张，扩大其孔隙并将白蛋白泄漏到尿液中。为了验证这一假设，我们开发了GBM的多孔弹性模型。它预测了健康肾小球中GBM的压缩和疾病状态下GBM的扩张，基本上证实了这一假设。然而，凝胶压缩和膨胀机制本身不能解释白蛋白尿的两个特征：滤过通量的减少和GBM的增厚。第二个机制，在GBM下游的狭缝隔膜处的流动面积的收缩，必须包括在内。这两种机制之间的合作产生了在突变小鼠模型中体内预期的GBM孔隙度增加的量，并且还捕获了过滤通量降低和GBM厚度增加的两个体内特征。最后，该模型支持这样的想法，即在健康的肾小球中，凝胶压缩可能有助于在不同的过滤压力下保持大致恒定的过滤通量。
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.