Obesity is an independent risk factor for the development and progression of chronic kidney disease and one of the emerging reasons for end-stage renal disease owing to its dramatic increase worldwide. Among the potential underlying pathophysiologic mechanisms, activation of the renin-angiotensin-aldosterone-system (RAAS) plays a central role. Increased angiotensin II (AngII) levels also are central in hypertension, dyslipidemia, and insulin resistance, which, taken together with obesity, represent the metabolic syndrome. Increased AngII levels contribute to hyperfiltration, glomerulomegaly, and subsequent focal glomerulosclerosis by altering renal hemodynamics via afferent arteriolar dilation, together with efferent renal arteriolar vasoconstriction as well as by its endocrine and paracrine properties linking the intrarenal and the systemic RAAS, adipose tissue dysfunction, as well as insulin resistance and hypertension. The imbalance between increased AngII levels and the angiotensin converting enzyme 2/Ang (1-7)/Mas receptor axis additionally contributes to renal injury in obesity and its concomitant metabolic disturbances. As shown in several large trials and experimental studies, treatment of obesity by weight loss is associated with an improvement of kidney disease because it also is beneficial in dyslipidemia, hypertension, and diabetes. The most promising data have been seen by RAAS blockade, pointing to the central position of RAAS within obesity, kidney disease, and the metabolic syndrome.
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