Simulation of whole mammalian kidneys using complex networks

Abstract

Modelling of kidney physiology can contribute to understanding of kidney function by formalising existing knowledge into mathematical equations and computational procedures. Modelling in this way can suggest further research or stimulate theoretical development. The quantitative description provided by the model can then be used to make predictions and identify further areas for experimental or theoretical research, which can then be carried out, focusing on areas where the model and reality are different, creating an iterative process of improved understanding. Better understanding of organ function can contribute to the prevention and treatment of disease, as well as to efforts to engineer artificial organs.

Existing research in the area of kidney modelling generally falls into one of three categories: • Morphological and anatomical models that describe the form and structure of the kidney • Tubule and nephron physiological models that describe the function of small internal parts of the kidney • Whole kidney physiological models that describe aggregate function but without any internal detail

There is little overlap or connection between these categories of kidney models as they currently exist.

This thesis brings together these three types of kidney models by computer generating an anatomical model using data from rat kidneys, simulating dynamics and interactions using the resulting whole rat kidney model with explicit representation of each nephron, and comparing the simulation results against physiological data from rats. This thesis also describes methods for simulation and analysis of the physiological model using high performance computer hardware.

In unifying the three types of models above, this thesis makes the following contributions: • Development of methods for automated construction of anatomical models of arteries, nephrons and capillaries based on rat kidneys. These methods produce a combined network and three-dimensional euclidean space model of kidney anatomy. • Extension of complex network kidney models to include modelling of blood flow in an arterial network and modelling of vascular coupling communication between nephrons using the same arterial network. • Development of methods for simulation of kidney models on high performance computer hardware, and storage and analysis of the resulting data. The methods used include multithreaded parallel computation and GPU hardware acceleration. • Analysis of results from whole kidney simulations explicitly modelling all nephrons in a rat kidney, including comparison with animal data at both whole organ level and the nephron level. Analysis methods that bring together the three dimensional euclidean space representation of anatomy with the complex network used for simulation are developed and applied. • Demonstration that the computational methods presented are able to scale up to the quantities of nephrons found in human kidneys.