Grant: CIHR Fellowship

Although over 2 million Canadians have chronic kidney disease, CKD, they die from diseases of their heart and blood vessels. This is caused by the build-up of toxins that the kidneys no longer filter out of the blood. This causes the lining of the blood vessels to not work properly. This makes them less to respond to the changing demands of the body leading to heart disease and death. Additionally, CKD patients suffer from blood clotting problems. This is because of the damage happening to the blood vessels, but how and why this happens is poorly understood. We have identified factors that can be monitored to see if we can diagnose the disease earlier and treat the underlying problem sooner by developing better treatments to better protect the blood vessels. We will use rats to model chronic kidney disease by feeding them a diet high in a substance which damages the kidneys. By changing the amount of phosphate in the diet, we will also show we can accelerate or delay the onset of the calcium build-up, and thereby alter when problems with the blood vessels occur. We will measure other substances in the blood that tell us about overall blood vessel health. Finally, when we try new treatments, we will monitor substances produced by the blood vessels to see if they can be returned to normal levels and function properly. In parallel experiments, we will look at CKD patient blood and see how the cells in the blood are functioning, and see if we can measure the damage to these cells. We will then see if we can treat these cells to work normally again, to become a potential treatment for these individuals blood vessels. This research will lead to a new understanding of the way this disease process works, and a starting point for new potential treatments and earlier diagnosis.