(252d) Simulating Solute Selectivity through Rat Kidney Glomeruli Using Febio

Chronic kidney disease (CKD) is a family of kidney diseases that leads to kidney failure. CKD is 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 blood, leading to clinical manifestations such as albuminuria, which is an excess of albumin in the urine. Investigating kidney damage directly is particularly difficult due to the nanoscale structures that facilitate filtration, necessitating indirect methods of investigation such as computational fluid dynamics (CFD). Foundational papers for assessing glomerular dysfunction computationally require quantifying the hydraulic conductivity and sieving coefficients for an idealized model of the GFB. However, the earlier models for assessing glomerular dysfunction neglect the ultrastructural complexity and electrostatic properties of the GFB [2].

We use open-source software FEBio (Finite Elements for Biomechanics) to simulate fluid transport in the filtration layers of the GFB. FEBio applies 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 the glycocalyx, GBM, endothelial layer, and epithelial layer in series. FEbio uses a generalized convection-diffusion equation to describe fluids and solutes moving from the lumen through the GFB into the urinary space.

The ultrastructural parameters for our 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 each filtering layer was designed. These parameters were then used to design our GFB volume using Autocad, MATLAB, and Python. The conditions of the simulation were analogous to the physiological conditions of the in vivo environment [2]. Our simulations will show the concentration profile of “test” solutes (e.g., albumin, glucose, signaling molecules) through the GFB under flow conditions. These “test” solutes are of varying Stokes-Einstein radius and are used to calculate sieving coefficients for each layer of the GFB for relevant filtrate material. The results of our CFD model are compared to previous mathematical models and experimental data under similar physiological conditions. We see similar sieving coefficients and concentration profiles as the analytical and numerical results of previously published works but with enhanced resolution. The consideration of recent 3D morphological observations of the GFB may lead to a better understanding of the filtering properties of the kidney [3]. In the future, we will study the effect of morphological variations associated with glomerular dysfunction on the sieving properties of the barrier.

References:

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

[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.

[3] Remuzzi, A. et al. “Role of ultrastructural determinants of glomerular permeability in ultrafiltration function loss.” JCI Insight vol. 5,13 (2020): e137249.