Abstract
Despite medical advances achieved recently, cardiovascular diseases are the maincause of morbidity and mortality in chronic kidney disease in the industrializedcountries. About half of deaths in these patients are due to a major cardiac event. While traditional risk factors are well identified, non-traditional risk factors have been highlighted. New pathophysiological pathways such as fibrosis and cardiac remodeling are being studied. Fibrosis and cardiac remodeling are particularly involved in heart failure with preserved ejection fraction.The main objective of this work is to observe early modifications of cardiac biomarkers during chronic kidney disease before dialysis. This work includes several studies allowing to answer to the main objective.In the first study, we proved the interest of using a clinical and biological tool in the prognostic assessment of major cardiac events and to prevent the complications of the chronic kidney disease. In the second work, we showed that an insulin-resistant and obese profile approaching metabolic syndrome exacerbates cardiac remodeling in rats with chronic renal failure. In this study, we were also able to propose that endothelio to mesenchymal transition phenomena at the origin of myofibroblasts could be involved in the process of cardiac fibrosis subsequent to chronic kidney disease. In the third experiment, we observed a discrete cardiac alteration after three months of renal insufficiency in rats made with an altered renal function induced at 12 weeks of life. In contrast, structural abnormalities of the heart are clearer when the renal insufficiency occurs at an earlier age (6 weeks of life), suggesting that cardiac alterations subsequent to a chronic kidney disease are more marked when the renal injury occurs in a young subject. Finally, all of this work contributes to the characterization of cardiac fibrosis and the functional impairment achieved during chronic renal failure.