Self Funded PhD Opportunity:

A Multi-Omics approach to understanding cardiovascular risk in patients with End-Stage KidneyDisease

We have an exciting opportunity to apply for a self-funded PhD project. You will work with an experienced group of supervisors to use a multi-omics approach to understand cardiovascular risk in end-stage kidney disease.

End-stage Kidney failure, also known as End-stage Kidney Disease (ESKD), is the final, irreversible stage of chronic kidney disease, where kidney function has worsened to the point that the kidneys can no longer function independently. Cardiovascular complications rather than impaired renal function are the leading cause of death in ESKD. This is due to CKD/ESKD is a chronic systemic proinflammatory state contributing to vascular and myocardial remodelling, atherosclerosis, vascular calcification and senescence, cardiac fibrosis and valve calcification and complex dyslipidaemia. Also, in CKD, due to uraemia, there is disruption of the microbiome and gut barrier function that allows translocation of endotoxin and bacterial metabolites to the systemic circulation, contributing to inflammation and associated cardiovascular disease. In this respect, CKD mimics accelerated ageing of the cardiovascular system. In 2009, an estimated 7,000 extra strokes and 12,000 extra myocardial infarctions per year were due to CKD in the UK, costing the NHS over £170 million.

Circulating blood cardiac biomarkers provide an insight into various aspects of cardiovascular structure and function, including myocyte injury, myocyte stress inflammation, and fibrosis. There are several promising new cardiovascular biomarkers (soluble suppression of tumorigenesis-2 (ST-2), galectin-3, and myosin chain), but their role in risk stratification in ESKD is unknown. In ESKD, lipoprotein particle size and composition is altered, with an upregulation of small, dense, low-density lipoprotein (LDL) particles that remain in the circulation for longer and have intrinsic properties capable of inducing endothelial inflammation. High-density lipoprotein (HDL) becomes dysfunctional, with impaired maturation, altered molecular composition, depressed anti-oxidant/anti-inflammatory functions, and clearance of triglyceride-rich lipoproteins and their atherogenic remnants show altered molecular composition and elevated plasma levels in ESKD. As a result of microbiome dysregulation, there is elevated levels of endotoxin, Trimethylamine N-oxide (TMAO), Indoxyl sulfate (IS) and Cresyl sulfate (pCS), which are associated with cardiovascular disease in ESKD. 

The objectives

1. To identify metabolomic and genomic patterns associated with cardiovascular disease in ESKD.
2. Assess the utility of putative metabolomic and genomic pattern in predicting deterioration in cardiac function and incidence major adverse cardiac events (MACE) in patients with ESKD.
3. Determine the utility of existing and new cardiac biomarkers in predicting deterioration in cardiac function and incident MACE in patients with ESKD. 
4. To characterise the microbiome in patients with ESKD. 

Please follow the link for more details about how to apply: https://www.findaphd.com/phds/project/a-multi-omics-approach-to-understanding-cardiovascular-risk-in-patients-with-end-stage-kidney-disease/?p143725