Shear Stress on Podocyte Foot Processes Arising from Flow in Filtration Slits Studied by Numerical Flow Simulations
- Glomerular Diseases: Podocyte Biology - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1403 Podocyte Biology
- Fuhrmann, Alexander, Karlsruher Institut fur Technologie, Karlsruhe, Germany
- Pritz, Balazs, Karlsruher Institut fur Technologie, Karlsruhe, Germany
- Endlich, Karlhans, Universitatsmedizin Greifswald, Greifswald, Germany
- Kriz, Wilhelm, Universitat Heidelberg, Heidelberg, Germany
The glomerular filtration barrier is exposed to flow dynamic forces arising from filtration pressure (tensile stress) and filtrate flow (shear stress). Filtrate flow acts on podocyte cell bodies in Bowman's space and on foot processes (FPs) lining the filtration slit. Besides a previous estimate of 8 Pa (Endlich & Endlich, Semin. Nephrol. 2012), the magnitude of shear stress to FPs remains unknown.
We used numerical flow simulations to study forces arising from glomerular filtration. Simulations were run with a realistic model of a filtration unit and the corresponding filtration parameters of the rat kidney. The filtration unit consists of fenestrated endothelium, the GBM, and two opposing halves of FPs bridged by the slit diaphragm (SD). The GBM and SD were regarded as porous media.
Modeling the GBM and SD as one homogenous porous medium, a peak wall shear stress of 65.2 Pa acting on FPs in the filtration slit was found; pressure dropped by 2.5 mm Hg across the SD. Increasing filtration slit width from 30 to 40 nm reduced peak wall shear stress by only 9% to 59.4 Pa. Modeling GBM and SD as two separate homogenous porous media with an increased viscous resistance of the SD further increased the pressure drop across the SD, but also wall shear stress on FPs. Two factors were revealed that may account for the high levels of wall shear stress: 1) convergence of filtrate flow out of the GBM into the filtration slit (similar to a nozzle), 2) transition from a porous medium (GBM, SD) with a rather uniform velocity profile into free flow (Bowman’s space) with a developing parabolic velocity profile.
Our data demonstrate that FPs are likely to experience high levels of wall shear stress in the filtration slit that markedly exceed levels of endothelial wall shear stress. Shear stress on FPs represents the only flow dynamic force that directly tends to disconnect viable podocytes from the GBM––a hallmark of podocyte loss in many glomerular diseases.
- Government Support – Non-U.S.