(58e) Simulating Solute Transport through the Kidney Glomerulus Using Febio

Chronic kidney disease (CKD) is a family of kidney diseases with various root causes that lead to eventual kidney failure and are characterized by dysfunction of the glomeruli, the functional subunits of the kidneys where blood is filtered. A glomerulus includes the glomerular filtration barrier (GFB) made of the endothelial layer, basement membrane, podocyte epithelial layer, and glycocalyx. The deterioration of the filtration barrier means that the kidney cannot effectively filter solutes from the capillaries, such as proteins, excess water, and other waste products. The functionality of the GFB is measured by the glomerular filtration rate or the rate at which fluid from the capillaries in the kidney is filtered to be excreted. Assessing glomerular dysfunction during CKD requires quantifying the effect of damage in the anatomical ultrastructure of GFB and the unwanted transport of protein through the GFB. Though various methods of assessing glomerular dysfunction exist, current computational models often neglect the glycocalyx as well as the effect of solute and GFB charge.

We use open-source software FEBio (Finite Elements for Biomechanics) to simulate fluid transport in different layers of the GFB. FEBio applies continuum biphasic (fluid dynamics/solid biomechanics) theory to describe viscous fluid interactions with porous-hydrated biological tissues. The biphasic fluid-solid interactions (BFSI) solver in FEBio is used to model structures of the glycocalyx, glomerular basement membrane, porous medium, and fluid-solid interactions through the intricate small channels that form the fenestrated endothelial layer and the GBM. Transport equations describe the movement of fluids and solutes from the blood vessel lumen through the GFB.

The anatomical ultrastructural parameters for the proposed model were estimated from high-resolution electron microscopy of the glomerular capillary wall [1]. With the information gathered from the electron microscopy images, a “subunit” consisting of the averaged parameterized features of the filter was used to simulate GFB. In addition, ultrastructural parameters were used to design the 3D fluid domain for the simulation using MATLAB and GIBBON, a dedicated biomechanics add-on. The volumetric domain was exported to FEBio, where material properties, boundary conditions, and an analysis step were included for the model. The conditions of the simulation were analogous to the physiological conditions of the in vivo environment [2]. Our simulations showed the flux of solutes (e.g., albumin, glucose, signaling molecules) through the GFB, which can be used to find the glomerular filtration rate (GFR). We intend to simulate the dynamic effects of biomolecular reactions on kidney ultrastructure as it relates to CKD. We use the model to analyze important dynamic phenomena during disease progression, including the widening of the filtration slit, thickening of the glomerular basement membrane, and detachment of the podocyte food processes.

By recreating the human anatomy in a computational platform and applying the correct transport phenomena in each tissue layer, the physiological effects on the transport of solutes and glomerular filtration rate can be determined. Understanding the glomeruli’s fluid transport and chemical and physical interactions is critical to provide insights into human development, disease progression, and wound healing possibilities.

Acknowledgments: This work was supported by the National Science Foundation under Grant No. 2133411, the University at Buffalo, and the T32-Initiative for Maximizing Student Development (T32-IMSD) Training Program (sponsored by NIH NIGMS).

References:

[1] Rice, W L et al. “High resolution helium ion scanning microscopy of the rat kidney.” PloS One vol. 8,3 (2013): e57051. doi:10.1371/journal.pone.0057051

[2] Drumond, M C, and W M Deen. “Structural determinants of glomerular hydraulic permeability.” American Journal of Physiology Renal Physiology vol. 266,1 Pt 2 (1994): F1-12. doi:10.1152/ajprenal.1994.266.1.F1