Range of adiposity and cardiorenal syndrome

Abstract

Obesity and obesity-related co-morbidities, diabetes mellitus, and hypertension are among the fastest-growing risk factors of heart failure and kidney disease worldwide. Obesity, which is not a unitary concept, or a static process, ranges from alterations in distribution to the amount of adiposity. Visceral adiposity, which includes intraabdominal visceral fat mass and ectopic fat deposition such as hepatic, cardiac, or renal, was robustly associated with a greater risk for cardiorenal morbidity than subcutaneous adiposity. In addition, morbid obesity has also demonstrated a negative effect on cardiac and renal functioning. The mechanisms by which adipose tissue is linked with the cardiorenal syndrome (CRS) are hemodynamic and mechanical changes, as well neurohumoral pathways such as insulin resistance, endothelial dysfunction, nitric oxide bioavailability, renin-angiotensin-aldosterone, oxidative stress, sympathetic nervous systems, natriuretic peptides, adipokines and inflammation. Adiposity and other associated co-morbidities induce adverse cardiac remodeling and interstitial fibrosis. Heart failure with preserved ejection fraction has been associated with obesity-related functional and structural abnormalities. Obesity might also impair kidney function through hyperfiltration, increased glomerular capillary wall tension, and podocyte dysfunction, which leads to tubulointerstitial fibrosis and loss of nephrons and, finally, chronic kidney disease. The development of new treatments with renal and cardiac effects in the context of type 2 diabetes, which improves mortality outcome, has highlighted the importance of CRS and its prevalence. Increased body fat triggers cellular, neuro-humoral and metabolic pathways, which create a phenotype of the CRS with specific cellular and biochemical biomarkers. Obesity has become a single cardiorenal umbrella or type of cardiorenal metabolic syndrome. This review article provides a clinical overview of the available data on the relationship between a range of adiposity and CRS, the support for obesity as a single cardiorenal umbrella, and the most relevant studies on the recent therapeutic approaches.

Keywords: Obesity; Morbid obesity; Cardiorenal syndrome; Heart failure; Chronic kidney disease

Core tip: Visceral adiposity and morbid obesity are risk factors for heart and kidney disease, configuring a cardiorenal syndrome. Adipose tissue results in hemodynamic and mechanical derangements in addition to activating neuro-humoral systems such as endothelial dysfunction, adipokines, renin-angiotensin-aldosterone, sympathetic nervous system, natriuretic peptides, inflammation, and oxidative stress. Obesity induces cardiac remodeling and fibrosis, leading to heart failure (HF). HF with preserved ejection fraction is characteristically linked to obesity. Hyperfiltration, increased glomerular capillary wall tension, podocyte dysfunction, and, finally, chronic kidney disease has been linked to obesity. Most of the new treatments for diabetes mellitus type 2, which have favorable cardiovascular outcomes, improve the cardiometabolic renal syndrome associated with obesity.