(157bk) A Mathematical Model of the Glomerular Filtration Barrier in Diabetic Kidney Disease

The glomerulus has been determined to be the central tissue structure damaged within the kidney in diabetic kidney disease (DKD)(1). Due to the difficulty in acquiring experimental data regarding the progression of DKD within the glomerulus, mathematical modeling has arisen as a tool for tracking and predicting the progression of damage. There are several methods and hallmarks of damage within diabetic kidney disease, the most physically visible of which is the development of albuminuria or the leaking of the protein albumin into the urine. This development is partially due to damage caused to the glomerular filtration barrier (GFB). This barrier is composed of several layers, including the podocytes on the exterior of the glomerulus, the glomerular basement membrane, endothelial cells, and the endothelial glycocalyx. The podocyte has already been extensively studied and successfully modeled (2, 3). Here we focus on the GFB.

All components of this barrier play an integral role in blocking the passage of albumin. The endothelial fenestrations provide a hydraulic barrier, the glomerular basement membrane functions as a multi-pore mesh blocking molecules above a certain size, and the glycocalyx functions as a charge barrier against polar compounds (4). Damage to this barrier is integral in the development of albuminuria; however, the difficulty in gathering data on this barrier has resulted in a piecemeal approach to determining the progression of the diabetes associated damage.

In this work, a mathematical model is developed to track concentration, transport, and production of several damaging chemicals within diabetic kidney disease and their interactions with the GFB. Additionally, this model tracks the damage resulting from this dysregulated biochemical networks in the GFB.

References:

1. Schlondorff D. Putting the glomerulus back together: per aspera ad astra ("a rough road leads to the stars"). Kidney Int. 2014;85(5):991-8.
2. Pilvankar MR, Higgins MA, Ford Versypt AN. Mathematical model for glucose dependence of the local renin-angiotensin system in podocytes. Bull Math Biol. 2018;80(4):880-905.
3. Pilvankar MR, Yong HL, Ford Versypt AN. A glucose-dependent pharmacokinetic/pharmacodynamic model of ACE inhibition in kidney cells. Processes. 2019;7(3):131.
4. Smithies O. Why the kidney glomerulus does not clog: a gel permeation/diffusion hypothesis of renal function. Proc Natl Acad Sci USA. 2003;100(7):4108-13.