The Physiopathology of Cardiorenal Syndrome: A Review of the Potential Contributions of Inflammation

Inter-organ crosstalk plays an essential role in the physiological homeostasis of the heart and other organs, and requires a complex interaction between a host of cellular, molecular, and neural factors. Derangements in these interactions can initiate multi-organ dysfunction. This is the case, for instance, in the heart or kidneys where a pathological alteration in one organ can unfavorably affect function in another distant organ; attention is currently being paid to understanding the physiopathological consequences of kidney dysfunction on cardiac performance that lead to cardiorenal syndrome. Different cardiorenal connectors (renin-angiotensin or sympathetic nervous system activation, inflammation, uremia, etc.) and non-traditional risk factors potentially contribute to multi-organ failure. Of these, inflammation may be crucial as inflammatory cells contribute to over-production of eicosanoids and lipid second messengers that activate intracellular signaling pathways involved in pathogenesis. Indeed, inflammation biomarkers are often elevated in patients with cardiac or renal dysfunction. Epigenetics, a dynamic process that regulates gene expression and function, is also recognized as an important player in single-organ disease. Principal epigenetic modifications occur at the level of DNA (i.e., methylation) and histone proteins; aberrant DNA methylation is associated with pathogenesis of organ dysfunction through a number of mechanisms (inflammation, nitric oxide bioavailability, endothelin, etc.). Herein, we focus on the potential contribution of inflammation in pathogenesis of cardiorenal syndrome.