Impact of Weight Loss After a Bypass Surgery on Renal Hemodynamic Under Stress Conditions

Effect of Weight Loss Induced by a Bypass Surgery on Renal Salt Excretion, Renal Hemodynamic and on Neurohormonal Responses During an Induced Orthostatic Stress in Obese Patients

The sympathetic nervous (SNS) and the renin angiotensin aldosterone system (RAS) have a direct impact on renal hemodynamic, hormonal secretion and vasoactive peptide. Many mechanisms including the SNS, RAS and renal sodium handling could explain the pathogenesis of hypertension in obese patients. Lifestyle changes and bariatric surgery induce weight loss, which is associated with blood pressure lowering in obese patients. A diminution in the renal sympathetic stimulation and RAS activation could explain this effect.

The AIM of this study is to show that weight loss induced by bypass surgery in obese patients affects renal salt excretion under " low body negative pressure (LBNP)" conditions .

Secondary objectives are to investigate the impact of weight loss on renal hemodynamic (glomerular filtration rate (GFR), renal plasma flow) and neurohormonal responses under " low body negative pressure conditions ". We will also analyse renal blood oxygenation with Blood Oxygenation dependant IRM (BOLD-IRM) technique before and after weight loss.

The population of this study will consist in two groups including 36 patients. The first one will include 24 obese patients that are going to undergo a bariatric surgery. The second one will include 12 obese patients without any weight loss associated surgery.

Both group will undergo 3 investigation days. Each patient will have to undergo a screening visit that will provide dietary advice to ensure a standardized salt intake (120-180 mmol/day) for the duration of the study. The first investigation will define baseline, the second and third day of investigation will take place after 3 month and 12 month after bariatric surgery for surgical patients or after baseline for patients without surgery. One to two weeks before phase 1 and 3 patients will perform a BOLD-MRI. The surgery group will undergo bariatric surgery between the first investigation phase (baseline) and the second. An ambulatory blood pressure and 24-hour urine collection will precede each investigation day. An investigation day consists in renal hemodynamics, neurohormonal and natriuretic response measurements before, during and after 60 min of LBNP at -30mbar . The duration of the study per subject is going to take 12 months.

Inclusion Criteria:

• BMI >35 Kg/m2
• Understanding and signing the informed consent
• Estimated glomerular filtration rate >60 ml/min/1.73 m2

Exclusion Criteria:

• Acute disease
• Asthma or history of asthma
• Patient participating in another clinical trial 30 days before the beginning of the study
• Blood donation (450ml) 2 months before the beginning of the study
• Chronic medication which influence renal function (NSAIDS, Others)
• Allergy
• Documented renal arterial stenosis
• History of symptomatic orthostatic hypotension
• Kidney transplantation
• Kidney malformation / polycystic kidney disease
• Impaired judgement
• Liver failure with ascitis
• Hip circumference at the upper anterior iliac spine > 130cm
• Waist circumference >180cm and weighing > 220kg
• Contraindication/Allergy to furosemide, PAH or Inulin
• Contraindication to MRI if the patient is going to undergo BOLD-MRI
• Postprandial glycemia > 11.0 mmol/L in diabetic patients
• Blood pressure > 180/110 assessed by 24 hour blood pressure measurement