Why does kidney disease progress and destroy the kidneys in some people but not in others?
Thanks to the support of the Royal Brisbane Hospital (RBH) Research Foundation, the fledgling program moved to the RBH Clinical Research Centre, located on H floor of the Bancroft Centre, in early 2000. The proximity to world class Science and Scientists has quickened the germination of lines of research.
The first studies concentrated on establishing two human models of progressive kidney insufficiency. Proximal tubular epithelial cells (PTE) are isolated from either nephrectomy specimens or a single core of tissue taken at the same time as a diagnostic renal biopsy. The first model uses PTE from histologically normal tissue and the second from tissue that is abnormal according to independent expert histopathology opinion. In the models, primary cultures of PTE are stimulated with human serum protein in vitro much as these cells are in proteinuric renal diseases. The cells respond to high protein trafficking into the cells in a multiplicity of ways. The biological responses of normal PTE in the first model are the subject of current work.
We are currently focusing on four areas:
1. describing how the kidney cell responses change with different concentrations of human serum proteins. We are fractionating the serum proteins to identify which protein/s stimulate the cell responses
2. we are discovering that overloading the cells with protein causes their premature death and are exploring how this happens. We are submitting the first stages of this work for presentation at the Australian and New Zealand Society of Nephrology Annual Scientific Meeting in Darwin this year.
3. we are using technology from the Human Genome Project to show how protein loading results in the activation of genes whose roles in progressive kidney disease have not yet been described. The technology allows us to look at thousands of genes simultaneously.
4. in the second half of 2001, the Group will examine how drugs, including a novel agent called omapatrilat, influence the cell responses to protein loading.
In the future we plan to continue the focus on how PTE translate protein overload into the many different cell responses of premature death, inflammation, fibrosis, etc in this and the second model.
Resources
Royal Brisbane Hospital (RBH) Research Foundation Grant
RBH Kidney Trust Fund
