(A-21) Hemodynamics in kidney glomeruli under physiological and pathological filtration.

Introduction:: The glomerulus and surrounding Bowman’s capsule form a renal corpuscle, which serves as the fundamental filtration unit in the kidney. It plays an essential role in preserving healthy kidney function and maintaining overall homeostasis within the body. However, glomerular disease can lead to chronic kidney disease and a loss of kidney function. Previous studies have shown glomerular diseases are often linked to hyperfiltration and blood flow irregularities. Nevertheless, those prior studies have relied on simplified network models ¹ that fail to account for the complex glomerulus anatomy or the intricate filtration process from the glomerulus to Bowman’s capsule. Recent advancements in imaging technologies have allowed for the creation of more detailed 3D models of the glomerulus², revealing new features such as vascular chamber (VC). In this study, we aim to examine fluid flow through mouse glomeruli, utilizing these 3D models ³ and explore different scenarios of filtration across glomeruli.


Materials and Methods:: Computational fluid dynamics (CFD) was utilized to analyze the flow of fluid in five mouse glomeruli. The simulation was performed using Ansys 2022 R2 (Ansys Inc., Pittsburgh, PA) with the assumption that blood is a Newtonian fluid of 1.5 cP with laminar and incompressible flow. Additionally, a steady continuum and isothermal conditions were applied. A static pressure condition of 98 mmHg was applied at the inlet (afferent arteriole) while the outlet (efferent arteriole) was subjected to a pressure of 38 mmHg. Mesh convergence was achieved with approximately 3 million hexagonal cells. To simulate glomerular filtration, fluid flow was applied to the surfaces of the glomerulus, and the filtration velocity was set based on the flow rate without filtration. In physiological conditions, filtration velocity was set to 10%, whereas in pathological conditions, it was set to 50%. The paired t-test was used to perform statistical analysis utilizing Prism 9 (GraphPad Software, San Diego, CA).


Results, Conclusions, and Discussions:: Results: The morphologies of each mouse glomerulus were analyzed by dissecting virtual glomeruli models. The afferent vascular chamber (AVC) was found to have a significantly larger volume (5886 ± 592 vs. 1140 ± 354 µm³, p < 0.0001) compared to efferent vascular chamber (EVC), with larger number of branches (9.4 ± 0.9 vs. 5.6 ± 0.5, p < 0.0001). When filtration was not taking place, the simulated blood flow rate was 102 ± 31 nL/min with higher blood velocity at the top (Artery side) compared to the bottom (Bowman’s capsule side) of the glomerulus. The shear rate was higher at efferent arteriole than the afferent arteriole (67,000 ± 58,000 vs. 102,000 ± 28,000 /s) as the efferent arteriole had a smaller vessel diameter compared to afferent arteriole. With a high filtration rate, the blood flow rate in the afferent arteriole increased from 108 ± 32 nL/min (10% filtration) to 132 ± 37 nL/min (50% filtration), the efferent arteriole blood flow rate decreased from 98 ± 29 nL/min to 82 ± 22 nL/min. Consequently, the shear rate in the afferent arteriole increased 20% while it decreased 13% in the efferent arteriole under high filtration rate conditions.

Conclusions and Discussion: Overall, this study provides insights into the hemodynamics and morphological characteristics of mouse glomeruli under different conditions of filtration. By using CFD with 3D models from in vivo imaging data, we showed that glomeruli have an asymmetric morphology and flow characteristics, with the afferent side displaying larger vascular chambers and lower shear rates in physiological conditions. The study also highlights the potential damaging effects of hyperfiltration on the afferent arteriole due to high shear stress on the vessel wall. These findings contribute to a deeper understanding of the complex interplay between morphology, hemodynamics, and disease progression in the kidney filtration units.


Acknowledgements (Optional): : We acknowledge the Lynn and Mike Garvey Imaging Laboratory in the Institute for Stem Cells and Regenerative Medicine at the University of Washington. We acknowledge the financial support of National Institute of Health grants UG3 TR003288 and UG3TR002158 (JH).


References (Optional): : 1 Richfield, O., Cortez, R. & Navar, L. G. Simulations of Glomerular Shear and Hoop Stresses in Diabetes, Hypertension, and Reduced Renal Mass using a Network Model of a Rat Glomerulus. Physiological Reports 8, e14577, doi:https://doi.org/10.14814/phy2.14577 (2020).

2 Neal, C. R. et al. Novel hemodynamic structures in the human glomerulus. Am J Physiol Renal Physiol 315, F1370-F1384, doi:10.1152/ajprenal.00566.2017 (2018).

3 Terasaki, M., Brunson, J. C. & Sardi, J. Analysis of the three dimensional structure of the kidney glomerulus capillary network. Sci Rep 10, 20334, doi:10.1038/s41598-020-77211-x (2020).