Obesity and kidney disease: potential mechanisms

Assessment of adiposity should include measurements of both body mass index and waist circumference. The prevalence of obesity, based on a body mass index of 30 kg/m(2) or greater, has increased substantially over the past 2 decades in Western societies. Obesity remains the number one preventable risk factor for chronic kidney disease because obesity largely mediates diabetes and hypertension, the 2 most common etiologies for end-stage kidney disease. However, obesity itself likely has independent effects on renal hemodynamics and individuals with a low number of nephrons are likely to be the most susceptible to these changes. Multiple mechanisms have been postulated whereby obesity directly impacts kidney disease including hyperfiltration, increased glomerular capillary wall tension, and podocyte stress. Weight loss reduces glomerular filtration rate and effective renal plasma flow along with proteinuria, but these changes are most notable after bariatric surgery in adults with morbid obesity. Aside from adiposity itself, the high caloric intake that leads to obesity also may heighten chronic kidney disease risk via the circuitous loop between Sirt1 and adiponectin and podocyte effacement. Sirt1 is a nicotinamide adenine dinucleotide+dependent deacteylase that is up-regulated in the setting of caloric restriction. Sirt1 expression modulates adiponectin levels that in turn appear to influence podocyte effacement. Clinical trials are needed to assess the benefits and risks of intentional weight loss on kidney disease measures and progression.