Grant: Master's Award: Canada Graduate Scholarships

Chronic kidney disease (CKD) affects over 2 million Canadians. The leading cause of mortality in CKD patients is cardiovascular disease. Traditional cardiovascular risk factors, such as diabetes and hypertension, do not completely account for the increased mortality. Non-traditional risk factors such as disorders of calcium and phosphate metabolism occur early in the course of CKD and they contribute to vascular calcification (VC). VC is associated with arterial stiffness and an increase in all-cause and cardiovascular mortality. Recently, evidence has indicated that VC is an active process. Vitamin K-dependent matrix Gla protein (MGP) is an endogenous inhibitor of VC. Vitamin K is a co-factor in the carboxylation of MGP. MGP must be carboxylated for it to be active; therefore, adequate vitamin K stores are essential to inhibit calcification. Epidemiological studies have shown that CKD patients develop more severe VC at a much younger age than the rest of the population. To date, the role of vitamin K and MGP carboxylation status have not yet been evaluated in an animal model of CKD. Our laboratory hypothesizes that vitamin K supplementation will slow the progression of CKD-induced VC and the associated changes in vascular properties, which will be dependent, at least in part, on its ability to increase carboxylated MGP. Warfarin is an anti-coagulation drug that is used widely to prevent thrombosis. It acts by inhibiting vitamin K. Our laboratory hypothesizes that administration of therapeutic doses of warfarin will increase the progression of CKD-induced VC and the associated changes in vascular properties, which will be dependent, at least in part, on a decrease in carboxylated MGP. Discovering the role of vitamin K and MGP carboxylation status in a CKD model will give us a further understanding of vascular calcification in CKD patients. This will allow us to better treat these patients, potentially increasing their lifespan and quality of life.