Grant: Travel Awards - Institute Community Support

Chronic kidney disease (CKD) affects roughly three million Canadians and is accompanied by considerable human suffering, premature death, and costly medical care. The incidence of ESRD and its associated cardiovascular (CV) complications continues to rise despite improved treatments for many of it's risk factors such as diabetes and high blood pressure. Recently, small circulating molecules in the blood, known as "Extracellular Vesicles" (EVs), have been though to be better biomarkers than the ones currently used to diagnose and predict these complications. We are therefore using multiple approaches to better understand the organ-level effects of extracellular vesicles and their cargo to gather the detailed mechanistic insight necessary for the development of an integrative cardiovascular risk prediction model for diabetic ESRD patients. The foundation of this study is the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) cohort (n=571); a cohort of ESRD patients followed over four years, with a repository of clinical data with matched biological samples. We isolated these extracellular vesicles from plasma, characterized their properties using advanced molecular biology techniques and genetic sequencing. EV analysis revealed diabetic ESRD patients have increased circulating vesicle concentrations; in addition to having vesicles of a larger size. Data from our clinically translatable methologies identified numerous potential cargo biomarkers for cardiovascular complications of ESRD. We utilized statistical models to generate a panel of biomarkers which may serve as cardiovascular risk predictors for diabetic ESRD patients. This data will be weighted with the novel biomarker data and fully integrated to build a clinical risk prediction model for the development of CV complications in ESRD and re-assessed in a new cohort to replicate the findings and validate the risk prediction model.