Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Chronic kidney disease (CKD) is a worldwide health problem (affecting more than 2 million Canadians) with rising incidences and poor outcomes. CKD patients are classified as one of the highest risk groups for developing cardiovascular disease (CVD). More than half of these patients develop CVD and when they finally reach end stage kidney disease cardiac mortality is reported to be 10 to 30 times higher than in the general population. The traditional risk factors such as age, hypertension, smoking, diabetes present in this population do not completely account for the increased cardiovascular mortality. Non-traditional risk factors which develop after the onset of CKD, specifically metabolic imbalance, are associated with vascular calcification (VC) and arterial stiffness, which substantially increase cardiovascular and all-cause mortality. VC is associated with circulatory changes (high systolic pressure, pulse pressure and pulse wave velocity) as well as left ventricular hypertrophy, all independent factors of cardiovascular morbidity and mortality. Our goal is to determine the mechanisms involved in the development of VC in CKD using an animal model that reflects the human condition. These studies will involve a careful characterization of the temporal course of VC and its consequences in an adenine-induced model of CKD in rats. We will perform analysis of tissue calcium, blood vessel function and hemodynamic changes by continuous radiotelemetric monitoring in conscious rats. Despite the importance of the vascular complications to the morbidity and mortality of this disease, the last two outcomes have not been assessed in this animal model of CKD. The main mechanistic focus of this project will be on the role of changes in phosphate metabolism on the progression of vascular disease. We hope to address an unmet need for therapy that promotes regression and/or manages progression of vascular calcification, thereby directly benefiting CKD patients with CVD.