The link between the renin-angiotensin-aldosterone system and renal injury in obesity and the metabolic syndrome.
Obesity is a risk factor for type 2 diabetes mellitus (DM) and is associated with chronic kidney disease. Activation of the renin-angiotensin-aldosterone system (RAAS) is common in obesity. The RAAS is an important mediator of hypertension. Mechanisms involved in activation of the RAAS in obesity include sympathetic stimulation, synthesis of adipokines in the RAAS by visceral fat, and hemodynamic alterations. The RAAS is known for its role in regulating blood pressure and fluid and electrolyte homeostasis. The role of local/tissue RAAS in specific tissues has been a focus of research. Urinary angiotensinogen (UAGT) provides a specific index of the intrarenal RAAS. Investigators have demonstrated that sex steroids can modulate the expression and activity of the different components of the intrarenal RAAS and other tissues. Our data suggest that obese women without DM and hypertension have significantly higher levels of UAGT than their male counterparts. These differences existed without any background difference in the ratio of microalbumin to creatinine in the urine or the estimated glomerular filtration rate, raising a question about the importance of baseline gender differences in the endogenous RAAS in the clinical spectrum of cardiovascular diseases and the potential utility of UAGT as a marker of the intrarenal RAAS. Animal studies have demonstrated that modifying the amount of angiotensin, the biologically active component of the RAAS, directly influences body weight and adiposity. This article reviews the role of the RAAS in renal injury seen in obesity and the metabolic syndrome.
Tulane University School of Medicine, New Orleans, LA 70112, USA.
Tina
T
Thethi
Masumi
M
Kamiyama
Hiroyuki
H
Kobori
D058186:Acute Kidney Injury / Q000453:epidemiology / Q000209:etiology*; D018450:Disease Progression; D006439:Hemodynamics; D006801:Humans; D007333:Insulin Resistance; D007674:Kidney Diseases / Q000453:epidemiology / Q000209:etiology*; D024821:Metabolic Syndrome / Q000150:complications*; D009765:Obesity / Q000150:complications*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D018570:Risk Assessment; D012737:Sex Factors