Type 4 Cardiorenal Syndrome: Myocardial Dysfunction, Fibrosis, and Heart Failure in Patients with Chronic Kidney Disease

Chronic kidney disease manifested by a reduction in glomerular filtration function, albuminuria, or markers of chronic renal injury have been consistently associated with the development of heart failure, heart failure hospitalizations, and cardiac mortality. The principal mechanisms by which the cardiac ventricles ultimately fail include pressure overload, volume overload, and cardiomyopathy. Chronic and acute kidney diseases contribute via these pathways to cardiomyopathic processes that can be visualized as adverse remodeling, systolic and diastolic dysfunction, and now with modern imaging and molecular techniques, myocardial fibrosis. It appears that both within the myocardium and the renal parenchyma, as there is loss of functional tissue, there is the deposition of collagen and other proteins resulting in fibrosis. Once this form of repair is initiated, it appears that it is progressively pathogenic itself leading to worsened cardiorenal syndrome type 4, a viscous cycle initiated by kidney disease and leading to heart failure hospitalizations and death. This paper will explore the complicated pathophysiologic processes involved in this syndrome with the aim of elucidating potential future diagnostic and therapeutic targets.