The effect of glomeruli death on kidney function

A problem presented at the UK MMSG Strathclyde 2004.

Presented by:
Dr Colin Geddes (Renal Unit, Glasgow Western Infirmary)
SA Baigent, HM Byrne, CC Geddes, N Katsikanis, JR King, S McKee, DR McLean, JA Sherratt, IMM van Leeuwen, JAD Wattis

Problem Description

The kidneys consist of approximately one million filtering units called nephrons. Each nephron has a glomerulus, where the majority of urine filtration from the blood occurs. When kidneys become diseased some of these glomeruli die. Since there is no mechanism for replacement or regeneration of glomeruli, the remaining glomeruli are required to increase the amount of fluid they filter if the overall filtration rate is to remain constant. It is thought that this increased rate can cause damage to the remaining glomeruli. The study group was asked to consider models for the attrition of glomeruli.

Study Group Report

In this report we have presented and analysed a series of models of progressive kidney damage. The simplest models are based on population models with a death rate that depends on the average filtration rate of each glomerulus. When this rate exceeds a certain level, we assume that the nephrons are lost from the system. These models produce graphs that have the correct qualitative behaviour, and by tuning the parameters, it should be straightforward to fit the data. A second, more detailed, level of modelling sought to provide some understanding of the process by which the glomeruli become sclerosed. We assumed that this was due to a combination of increased pressure, which aims to improve the flow rate through the glomeruli, but has a detrimental side effect of causing the glomerulus to swell and become sclerosed. Finally we proposed a model in which the population of the glomeruli were assumed to function as a variety of filtration rates. As the kidneys suffered damage, those glomeruli filtering at the highest rates die, and others operate and increased rates in a attempt to still provide the body's required GFR. These models also showed the expected temporal behaviour of an initial slow phase followed by a much more rapid loss in later stages of the disease.

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