Effect of Furosemide on Obesity-induced Glomerular Hyperfiltration
Background: Obesity is associated with a high prevalence of chronic kidney disease. The glomerular hyperfiltration associated with obesity may play a role in the pathogenesis of obesity associated chronic kidney disease. Attenuation of hyperfiltration by pharmacological means may slow down the development and progression of chronic renal failure. The investigators have previously shown that acetazolamide, a proximally acting diuretic that activates TGF by increasing solute delivery to the macula densa, abates glomerular hyperfiltration. The present study was designed to test the hypothesis that this decrease in hyperfiltration is specific to acetazolamide and not due to a non specific diuretic effect. The aim of the present study is to evaluate the effects of the administration of furosemide p.o. to subjects with severe obesity on glomerular hemodynamics.
Methods: Ten obese subjects will participate in the study. They will undergo measurement of glomerular filtration rate (inulin clearance) (GFR), renal plasma flow (RPF) (p-aminohippuric acid clearance), filtration fraction, fractional excretion of lithium (FE LI) and blood pressure, before and after administration of oral furosemide 20 to 40 mg bid for 3 days. The effects of furosemide on glomerular hemodynamics in obese subjects will be compared to the previously studied effects of acetazolamide.
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
- change in GFR [ Time Frame: 3 days ] [ Designated as safety issue: No ]
|Study Start Date:||September 2009|
|Study Completion Date:||July 2010|
|Primary Completion Date:||May 2010 (Final data collection date for primary outcome measure)|
|Experimental: Furosemide, obesity, glomerular hyperfiltration||
Subjects will receive 300 mg of lithium carbonate at 22.00 the day before the renal function tests.Intravenous catheters will be placed in each upper limb for infusion of clearance markers and blood sampling.A priming dose of inulin (50 mg/kg) and p-aminohippuric acid (8 mg/kg) will be administered. Thereafter, inulin and p-aminohippuric acid will be infused continuously. A 200-300 ml water load will be given during the first 60-min prime.
Subjects will be started on furosemide p.o. 20 mg every 12 hours, starting on day 1 at 15.00 after the renal function studies. Nine doses will be taken, the last dose on day 4 at 7 am.
In case the blood pressure does not decrease following 20 mg bid furosemide administration, the study will be repeated after 4 weeks using a dose of 40 mg p.o. bid.
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