Novel therapies for the treatment of cardiorenal syndrome

Summary The aim of this project is to investigate the mechanisms underlying the direct effects of uraemic toxins in vitro in cardiac, renal, vascular cells and monocytes, with a focus on actions mediated via the AhR.

Project Details

The interaction between heart disease and kidney disease is bidirectional, indicating acute or chronic dysfunction of the heart or kidneys can induce acute or chronic dysfunction in the other organ. This interdependent relationship has come to be known as cardiorenal syndrome (CRS) for which there are limited therapeutic options.  Uraemic toxins, such as indoxyl sulphate (IS), are elevated in the serum of chronic kidney disease (CKD) patients and contribute to the pathogenesis and progression of CKD and CRS by exerting deleterious effects in cardiac, renal, vascular and immune cells. The adverse effects of IS are potentially mediated by oxidative stress following activation of the aryl hydrocarbon receptor (AhR). The aim of this project is to investigate the mechanisms underlying the direct effects of uraemic toxins in vitro in cardiac, renal, vascular cells and monocytes, with a focus on actions mediated via the AhR. By inhibiting the AhR pathway, we can determine the downstream adverse effects of the receptor in each of the cell type and their potential contributory role in the progression of CRS. This project will potentially identify a novel strategy to for the treatment of patients with CRS or renal disease.

This project is ideally suited for a PhD student or sections can be adapted for an Honours/Masters research project.