Abstract: TH-PO0311
Morphological Changes Under Pathological Conditions Affect Filtrate Flow and Fluid Shear Stress on Podocyte Foot Processes
Session Information
- Glomerular Diseases: Cell Biology
October 22, 2026 | Location: Exhibit Hall A, 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, BW, Germany
- Pritz, Balazs, Karlsruher Institut fur Technologie, Karlsruhe, BW, Germany
- Kriz, Wilhelm, Universitat Heidelberg, Heidelberg, BW, Germany
- Endlich, Karlhans, Universitatsmedizin Greifswald, Greifswald, MV, Germany
Background
Recently, we have demonstrated by numerical flow simulations that filtrate flow exerts high levels of wall shear stress (WSS) on the plasma membrane of podocyte foot processes under physiologic conditions in rats (Fuhrmann et al., JASN 36: 219-230, 2025).
Methods
In the present study, we aimed to understand how morphological changes under pathological conditions, e.g. podocyte foot process (FP) effacement, alter fluid dynamics across the glomerular filtration barrier. We extended our 2D model of the filtration barrier, comprising one filtration slit, to a periodic 2D model consisting of five filtration slits between five foot processes. Numerical flow simulations were done for three different cases: FP effacement 20% up to 80%, loss of slit diaphragm next to effaced area, and denuded GBM by removing 20% of FPs.
Results
FP effacement. Filtrate flow across the glomerular filtration barrier steadily decreased with increasing FP effacement. However, the decrease in filtrate flow was attenuated, as higher flow through remaining filtration slits partially compensated for reduced filtration slit density. Thus, filtrate flow was reduced only to 61% at 80% effacement, while flow through remaining filtration slits almost doubled. As a consequence, WSS on FPs increased to 131% at 80% effacement. Loss of slit diaphragm. Loss of slit diaphragm next to effaced area increased filtrate flow and lowered average WSS. For example, at 40% effacement, filtrate flow increased by 11% and average WSS fell by 7%. Two effects account for this phenomenon: flow partially redistributed to filtration slit w/o slit diaphragm, and loss of slit diaphragm itself diminishes WSS in filtrations slits (Fuhrmann et al., JASN 36: 219-230, 2025). Denuded GBM. Filtrate flow increased by 86%, if GBM was denuded by removing 20% of FPs. Average WSS fell by 14%, since a substantial fraction of flow was shunted to the denuded area. WSS on FPs lining the denuded area was lowered even further by 35% due to the wide distance between the lining FPs.
Conclusion
Our results suggest that the mechanical load exerted by wall shear stress on podocyte foot processes is moderately increased by effacement, whereas it is decreased by loss of slit diaphragm in filtrations slits and by loss of individual foot processes.
Funding
- Government Support – Non-U.S.