Role of Bile Acid–Regulated Nuclear Receptor FXR and G Protein–Coupled Receptor TGR5 in Regulation of Cardiorenal Syndrome (Cardiovascular Disease and Chronic Kidney Disease)

It is well known that chronic kidney disease (CKD) is associated with increased risk of cardiovascular disease. In fact, studies have shown that cardiovascular event rates and allcause mortality increase as a function of CKD as determined by decrease in estimated glomerular filtration rate and presence of microalbuminuria. In recent years, the term cardiorenal syndrome (CRS) has been proposed to define the relationship between cardiac disease and renal disease. Ronco et al has defined CRS 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. CRS Type 1: acute CRS is defined as sudden worsening of cardiac function (acute cardiogenic shock or acutely decompensated heart failure), leading to acute kidney injury. CRS Type 2: chronic CRS is defined as chronic abnormalities in cardiac function (chronic congestive heart failure) causing progressive and potentially permanent CKD. CRS Type 3: acute renocardiac syndrome is defined as sudden worsening of kidney function (acute kidney injury or acute glomerulonephritis) causing acute cardiac disorder (heart failure, arrhythmia, or ischemia). CRS Type 4: chronic renocardiac syndrome is defined as CKD contributing to decreased cardiac function, cardiac hypertrophy, and increased risk of adverse cardiovascular events. CRS Type 5: secondary CRS is defined as systemic condition (obesity, diabetes mellitus, sepsis) causing simultaneous cardiac and renal dysfunction. In this review, I will be discussing mainly the type 5 CRS associated with obesity and diabetes mellitus and models of atherosclerosis and vascular calcification. In addition to discussing renal disease, I will also be discussing vascular disease because vascular dysfunction is a well-characterized complication of renal disease, and vascular dysfunction is also a leading cause of cardiac disease.