BACKGROUND The flow dynamic forces during glomerular filtration challenging the fixation of podocytes to the GBM are insufficiently understood. METHODS Numerical flow simulations were used to estimate these forces in the rat kidney. Simulations were run with a 3D model of the slit diaphragm as a zipper structure according to Rodewald and Karnovsky 1. The GBM was modeled as a porous medium. RESULTS Filtrate flow exerted a mean wall shear stress of 39 Pa with a maximum of 152 Pa on the plasma membrane of foot processes and up to 250 Pa on internal surfaces of the slit diaphragm. The slit diaphragm accounted for 25% of the hydrodynamic resistance of the glomerular filtration barrier. Based on the results of the 3D model, we developed a 2D model that allowed us to perform extensive parameter variations. Reducing the filtration slit width from 40 to 30 nm almost doubled wall shear stress. Furthermore, increasing filtrate flow velocity by 50% increased wall shear stress by 47%. When increasing the viscous resistance of the slit diaphragm, the pressure drop across the slit diaphragm increased to intolerably high values. A lower viscous resistance of the slit diaphragm than that of the GBM accounted for a gradual pressure decline along the filtration barrier. The sub-podocyte space tempered these challenges in circumscribed areas of filtration surface but had only a marginal impact on overall forces. CONCLUSIONS The filtration barrier experiences high levels of shear and pressure stress accounting for the detachment of injured but viable podocytes from the GBM--a hallmark in many glomerular diseases.

中文翻译：

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大鼠肾小球滤过过程中滤过狭缝中产生的剪切应力的数值流动模拟。


背景 肾小球滤过过程中挑战足细胞固定到 GBM 的流动动力尚不清楚。方法 采用数值流动模拟来估计大鼠肾脏中的这些力。根据 Rodewald 和 Karnovsky 1 使用狭缝隔膜作为拉链结构的 3D 模型进行模拟。GBM 被建模为多孔介质。结果 滤液流施加的平均壁面剪切应力为 39 Pa，在足突质膜上最大为 152 Pa，在狭缝隔膜内表面最高为 250 Pa。狭缝隔膜占肾小球滤过屏障流体动力学阻力的 25%。根据 3D 模型的结果，我们开发了一个 2D 模型，使我们能够执行广泛的参数变化。将过滤狭缝宽度从 40 nm 减小到 30 nm，几乎使壁面剪切应力翻了一番。此外，滤液流速增加 50% 会使壁面剪切应力增加 47%。当增加狭缝隔膜的粘性阻力时，狭缝隔膜上的压降增加到令人无法忍受的高值。狭缝隔膜的粘性阻力低于 GBM 的粘性阻力，导致沿过滤屏障的压力逐渐下降。亚足细胞空间在过滤表面的限定区域缓解了这些挑战，但对整体力的影响很小。结论 过滤屏障经历高水平的剪切和压力应力，导致受伤但有活力的足细胞从 GBM 中脱离——这是许多肾小球疾病的标志。