Scope and mechanisms of obesity-related renal disease.
OBJECTIVE
Obesity is established as an important contributor of increased diabetes mellitus, hypertension, and cardiovascular disease, all of which can promote chronic kidney disease (CKD). Recently, there is a growing appreciation that, even in the absence of these risks, obesity itself significantly increases CKD and accelerates its progression.


RESULTS
Experimental and clinical studies reveal that adipose tissue, especially visceral fat, elaborates bioactive substances that contribute to the pathophysiologic renal hemodynamic and structural changes leading to obesity-related nephropathy. Adipocytes contain all the components of the renin-angiotensin-aldosterone system, plasminogen activator inhibitor, as well as adipocyte-specific metabolites such as free fatty acids, leptin, and adiponectin, which affect renal function and structure. In addition, fat is infiltrated by macrophages that can alter their phenotype and foster a proinflammatory milieu, which advances pathophysiologic changes in the kidney associated with obesity.


CONCLUSIONS
Obesity is an independent risk factor for development and progression of renal damage. Although the current therapies aimed at slowing progressive renal damage include reduction in weight and rely on inhibition of the renin-angiotensin system, the approach will likely be supplemented by interventions aimed at obesity-specific targets including adipocyte-driven cytokines and inflammatory factors.
Division of Pediatric Nephrology, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tennessee 37232-2574, USA.
Tracy E
TE
Hunley
Li-Jun
LJ
Ma
Valentina
V
Kon
D017667:Adipocytes / Q000502:physiology; D006801:Humans; D007674:Kidney Diseases / Q000150:complications / Q000503:physiopathology*; D009765:Obesity / Q000150:complications / Q000503:physiopathology*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000502:physiology; D012307:Risk Factors