Abstract: FR-PO765
Forces of Filtrate Flow on Podocyte Foot Processes Studied by Three-Dimensional and Two-Dimensional Computational Fluid Dynamics
Session Information
- Glomerular Diseases: Mechanisms and Podocyte Biology
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Fuhrmann, Alexander, Karlsruher Institut fur Technologie, Karlsruhe, Baden-Württemberg, Germany
- Pritz, Balazs, Karlsruher Institut fur Technologie, Karlsruhe, Baden-Württemberg, Germany
- Endlich, Karlhans, Universitatsmedizin Greifswald, Greifswald, Mecklenburg-Vorpommern, Germany
- Kriz, Wilhelm, Universitat Heidelberg, Heidelberg, Baden-Württemberg, Germany
Background
The glomerular filtration barrier is exposed to forces arising from filtration pressure and filtrate flow. 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.
Methods
We used numerical flow simulations to study forces arising from glomerular filtration. Simulations were run with a 3D model of a filtration unit and the filtration parameters of the rat kidney. The filtration unit consisted of fenestrated endothelium, the GBM, and two opposing halves of FPs bridged by the slit diaphragm (SD). The GBM was modeled as a porous medium, the SD as a zipper structure (Rodewald & Karnovsky, J. Cell Biol. 1974).
Results
Filtrate flow exerted a mean wall shear stress (WSS) of 39 Pa with a maximum of 152 Pa on the plasma membrane of FPs and up to 250 Pa on the SD zipper structure. After crossing the GBM and converging into the filtration slit, filtrate flow is markedly accelerated. Thus, the filtration slit acts like a nozzle explaining the high shear stress on FPs. SD 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 with 20-fold reduced computing time to perform extensive parameter variations. In the 2D model, GBM and SD were both represented as porous media with independent viscous resistances. When SD resistance was increased (and GBM resistance was lowered in such a way to keep filtrate flow velocity constant) WSS increased noticeably. Reducing the filtration slit width by 25% from 40 to 30 nm almost doubled WSS, demonstrating the non-linearity of the nozzle effect. On the other hand, increasing filtrate flow velocity by 50 and 100% increased WSS by 47 and 94%, respectively, in a practically linear way. Changes in net filtration pressure did not affect WSS, as long as filtrate flow velocity was kept constant.
Conclusion
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. Two factors were identified to account for the high shear stress: the nozzle geometry of the filtration slit and the hydrodynamic resistance of the slit diaphragm.
Funding
- Government Support – Non-U.S.