Grant: Master's Award: Canada Graduate Scholarships

Chronic kidney disease (CKD) affects more than 3 million people in Canada. The leading cause of mortality is cardiovascular diseases and yet the commonly recognized risk factors (smoking, high blood pressure, high cholesterol, etc.) do not fully account for the increase in death. Non-traditional risk factors, such as alteration in the body's handling of minerals such as phosphate and calcium, appear to play a key role in the early development of the disease. Specifically, the heart and blood vessels have been found to accumulate calcium and phosphate just like in bone (called calcification); a result that can have serious consequences. CKD patients are also often found to be vitamin D deficient, leading to increased levels of parathyroid hormone (PTH). Treatments with some doses of vitamin D suppress PTH levels, but they also have been reported to cause calcification. In contrast, using other doses, some benefit has been achieved. The disagreement between studies has not helped such that the beneficial dosing range has not been established. Previous studies have also suggested there is an interaction with vitamin K. Given that vitamin K deficiency is also commonly found in CKD patients, a dual therapy approach seems very logical. The hypothesis is that to achieve a benefit with vitamin D therapy in CKD requires a sufficient level of vitamin K within the tissues of the body, not just in the blood. Our studies will investigate the vitamin D and K interactions at the level of cell and tissue function as well as at the whole animal level. Critical to determining the right doses of each is the careful analysis of all of the components involved in vitamin D and K synthesis and degradation, as well as the changes in cell, tissue and organ function.