Research Awards Recipients

Lay Abstract

Kidney disease affect one Canadian out of ten and is associated with severe mortality; it is the 10th leading cause of death in Canada. When the kidneys do not work anymore, patients require dialysis or a kidney transplant if they want to live. Hemodialysis is a type of dialysis where the blood is filtered three times per week by a machine. Although it prolongs life, it is not perfect and only half of the patients are still alive after 5 years on hemodialysis. The most frequent cause of death in those patients is cardiovascular disease, which regroup all heart problems. There is a disease called uremic cardiomyopathy and it is a heart problem caused by the decrease in kidney function. There are multiple causes to this disease, including inflammation. Patients with kidney disease have more inflammation than normal. Regulatory T cells (Tregs) are a sub-type of immune cells and their role is to control inflammation and the immune system. They have a role in protecting against cardiovascular diseases. Indeed, patients with cardiovascular diseases were shown to have less of those cells and injecting Tregs to patients can protect against many cardiovascular diseases. We also know that patients with kidney disease have less Tregs than normal. However, we don’t know why, how and if it impacts their cardiovascular risk. Hypothesis and Aims: Our hypothesis is that Tregs are dysfunctional in patients with kidney problems, and that it contributes to the development of uremic cardiomyopathy by increasing inflammation. The challenge is to understand why and how they are affected in patients on hemodialysis and if it has an impact on cardiovascular diseases. Our study will have two main aims: Aim 1: Characterize the impact of kidney failure on Tregs. To study Tregs, we will cultivate them in the lab for 7 days under different conditions and then study their characteristics; how they are, how they behave and if they are functional. For the different conditions, we will either expose them to serum (the yellow and translucid component of the blood) from hemodialysis patients or healthy controls. We also recently discovered a subtype of Tregs that is more frequent in hemodialyzed patients compared to healthy donors. As it was just discovered, we need to validate that it is more frequent in hemodialyzed patients by testing more patients. Then we want to see if this subtype increases with failing kidneys. We will thus look for it in patients with various degree of kidney failure. Aim 2. Define Treg role in the development of uremic cardiomyopathy. To achieve this aim, we will use a known mouse model of uremic cardiopathy. We will destroy most of the mice kidney and those mice will develop a heart problem in 4 weeks. We will then test the impact of 1) depleting Tregs 2) adding more Tregs to the development of uremic cardiomyopathy. Significance: Demonstrating a role for Tregs in the development of uremic cardiomyopathy would identify a new therapeutic target for this pathology. Understanding Treg dysfunction in patients with kidney failure is the first step to find out a way to reverse this problem and use them as a treatment.