Targeting the ‘wave of death’ check-points of chronic kidney disease (CKD)

Principal Advisor: Dr Andrew Kassianos

Email: Andrew.Kassianos@health.qld.gov.au

Organisational unit: QIMR Berghofer and Royal Brisbane Clinical Unit

Chronic kidney disease (CKD) is a worldwide public health burden, defined as decreased kidney function for >3months. In Australia alone, 1 in 3 adults (6 million people) are at risk of developing CKD, with the annual financial cost of CKD >$5 billion. Furthermore, there is no cure for CKD. Understanding the pathological mechanisms of CKD progression will fast-track the development of urgently needed clinical therapeutics.

Our team have established specialised epithelial cells of the kidney proximal tubule (PTEC) as central players in CKD. Under the pathological conditions of CKD, we show that human PTEC:

1. Undergo primary cell death;
2.  Release small extracellular vesicles (exosomes) from their (polarised) apical membrane that directly induce secondary cell death in adjacent healthy PTEC; and
3. Produce danger signals (including exosomes) from their (polarised) basolateral membrane that activate local immune cells and indirectly induce secondary cell death in adjacent PTEC.

This project will explore the therapeutic potential of targeting these ‘wave of death’ check-points in established pre-clinical human models of CKD. Outcomes of this proposal will have a major health impact in providing the rationale for innovative, evidence-based therapies for CKD. A PhD scholarship is available for this project.