Cardiorenal Syndrome Type-5: The Case of Diabetes Mellitus and the Effect of Nephropathy on the Cardiovascular Outcome

Introduction

Heart performance and kidney function are closely interconnected physiologically and pathophysiologically, both in health and in disease. A diseased heart has numerous adverse effects on kidney function, while in parallel, renal dysfunction can significantly impair cardiac function. The appreciation of the interaction between heart and kidney during dysfunction of each or both organs has practical clinical implications in both chronic and acute situations. Such interactions represent the pathophysiological basis for a clinical entity called cardiorenal syndrome (CRS). Recently, the definition of CRS was expanded to better reflect the dual heart–kidney interactions.1 The new definition was stated as “a pathophysiologic disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ.” To further stress the complicated interactions between these organ systems, a classification was introduced with four types in which the etymology reflects the presumptive primary and secondary abnormality and their chronologies, and a fifth subtype that includes systemic conditions that cause both cardiac and renal dysfunction; diabetes mellitus is the typical example of the latter subtype (). Although there is an appreciation that as more organs fail in this setting, mortality increases. There is limited insight into how combined renal and cardiovascular failure may differentially affect such an outcome. It is clear, however, that diabetes can affect both organs simultaneously and that the disease induced in one can affect the other and vice versa.

Abstract

Cardiorenal syndrome is defined as a pathophysiological disorder of the heart and kidneys in which acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ. This syndrome is classified into 5 types. Secondary (type 5) cardiorenal syndrome is characterized by the presence of combined cardiac and renal dysfunction due to acute or chronic systemic disorders. In the chronic setting, diabetes mellitus represents such a systemic condition that affects both the cardiac and renal system. Diabetes is a known risk factor for cardiovascular disease (CVD). Also, some diabetic patients develop nephropathy. The fibrogenic cytokine transforming growth factor-beta and the vascular endothelial growth factor are implicated in the development of the cardinal features of diabetic nephropathy. It is suggested that endothelial dysfunction may lead to simultaneous development and progression of renal and cardiac pathology in diabetes. While the risk of microvascular complications can be reduced by intensive glycemic control in patients with type 1 and type 2 diabetes mellitus, intensified intervention involving other vascular risk factors like hypertension and dyslipidemia demonstrated benefits in terms of both macrovascular and microvascular complications. In addition, treatments with angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists were shown to be associated with a significant reduction in the risk for renal disease progression that was paralleled by a reduction of the cardiovascular risk.

Keywords

cardiorenal, Diabetes Mellitus, albuminuria, nephropathy, cardiovascular disease, endothelial dysfunction