Novel therapies for the treatment of cardiorenal disease
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 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 study 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. Uraemic toxins, IS and kynurenic acid (KA) are both agonists of the AhR. They are known to activate many deleterious processes in various cell types that result in receptor-mediated redox-pro-inflammatory signalling and increased collagen synthesis. By inhibiting the AhR pathway, we can investigate the mechanism of AhR signalling and determine the downstream adverse effects of the receptor in each of the cell types 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.
- Dr Andrew Kompa, Research Fellow
- Dr Amanda Edgley, Senior Research Officer
- Ms Alison Cox, Senior Research Assistant
- Ms Sywia Glogowska, Technical Assistant
- Associate Professor Bing Wang, Centre of Cardiovascular Research in Therapeutics, Monash University, Alfred Hospital
NHMRC Program Grant
- Lekawanvijit S, Kompa AR, Krum H. Protein-bound uremic toxin: a long overlooked culprit in cardiorenal syndrome. American Journal of Physiology Renal Physiology 2016; 311: F52-62.
- Lekwanvijit S, Kumfu S, Wang BH, Manabe M, Nishijima F, Kelly DJ, Krum H, Kompa AR. The uremic toxin adsorbent AST-120 abrogates cardiorenal injury following myocardial infarction. PLOS One 2013; 8: e83687