PROJECT III ? NOVEL MRI STRATEGIES TO ASSESS OBESITY-INDUCED KIDNEY DYSFUNCTION AND IMPROVED FUNCTION AFTER BARIATRIC SURGERY PROJECT SUMMARY/ABSTRACT Obesity is a major risk factor for hypertension and chronic kidney disease. In experimental studies of obesity, weight gain is associated with increased renal sodium reabsorption and elevated blood pressure. One potential mechanism by which obesity may contribute to renal dysfunction and hypertension is through compressive effects of fat in and around the kidneys. This perirenal and renal sinus fat may compress the loops of Henle in the renal medulla and increase renal medullary fractional sodium reabsorption. This increase in sodium reabsorption would increase oxygen consumption and decrease tissue oxygen levels which can be assessed with non-contrasted blood oxygen level dependent (BOLD) magnetic resonance (MR) using a furosemide stimulus. Early, pre-clinical renal injury is difficult to assess, particularly renal medullary injury and dysfunction. We will evaluate a comprehensive MR strategy to determine if surgical weight loss after bariatric surgery (vertical sleeve gastrectomy) improves subclinical renal medullary injury and dysfunction using several non-contrasted MR techniques including renal perfusion (arterial spin labeling and phase contrast MR), renal tissue oxygenation response to a furosemide stimulus (BOLD MR), and renal fibrosis (native T1 mapping). We will specifically evaluate if perirenal and renal sinus fat volumes (and subsequent reductions in volumes measured with MR) are associated with MR-derived measures of altered renal medullary function and renal fibrosis using these techniques. We will also assess whether reductions in specific fat depots after vertical sleeve gastrectomy are independently associated with improvement in measures of subclinical renal dysfunction beyond other traditional measures of adiposity. We will also determine relationships of perirenal and renal sinus fat (and subsequent reductions after bariatric surgery) and markers of sympathetic nervous activity, renin-angiotensin-aldosterone system activity and inflammation to provide further mechanistic insights into the link between perinephric fat and renal dysfunction. To achieve these aims, we will perform a comprehensive MR-imaging exam in 50 obese hypertensive and 50 obese non-hypertensive participants before and 1 and 2 years after vertical sleeve gastrectomy.
PROJECT III ? NOVEL MRI STRATEGIES TO ASSESS OBESITY-INDUCED KIDNEY DYSFUNCTION AND IMPROVED FUNCTION AFTER BARIATRIC SURGERY PROJECT NARRATIVE The main goal of this project is to test the novel hypothesis that increased visceral fat, and specifically fat in and around the kidneys, elevates blood pressure and causes subclinical renal dysfunction, and that reductions in these fat depots with vertical sleeve gastrectomy (VSG) are independently associated with improved renal function. We will test this hypothesis by using a new strategy for magnetic resonance imaging (MRI) that can detect subtle changes in kidney function before onset of irreversible injury. Studies will be conducted in 100 obese participants (50 obese hypertensives and 50 obese ?non-hypertensives?) before and 1 and 2 years after surgical weight loss by VSG.
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