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Obesity-induced Hyperfiltration | Effect of Acetazolamide and Furosemide on Obesity-induced Glomerular Hyperfiltration

Obesity-induced Hyperfiltration research study

What is the primary objective of this study?

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 tubuloglomerular feedback(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 compare the effects of furosemide and acetazolamide on glomerular hemodynamics in subjects with severe obesity. Methods: A randomized double-blind crossover controlled design will be used. Fifteen obese subjects and ten subjects with normal body weight will participate in the study. Obese subjects will undergo measurement of glomerular filtration rate (GFR)(inulin clearance), renal plasma flow (RPF) (p-aminohippuric acid clearance), filtration fraction, fractional excretion of lithium (FE LI) and blood pressure, before and after intravenous administration of furosemide 2 mg. and acetazolamide 5 mg/kg BW. Ten subjects with normal body weight will undergo measurement of renal function without administration of diuretics.

Who is eligible to participate?

Inclusion Criteria: - 15 obese men (BMI>30), aged 18 to 55, with glomerular hyperfiltration (creatinine clearance>130 ml/min)) and 10 normal body weight men (BMI<25), aged 18 to 55. Exclusion Criteria: - Heart failure, CKD, COPD - Known allergy to furosemide, acetazolamide, inulin or amino-hippurate - Pharmacologic treatment for hypertension, cardiac disease, diabetes mellitus - Treatment with corticosteroids, antiepileptics or NSAID

Which medical condition, disease, disorder, syndrome, illness, or injury is researched?

Obesity-induced Hyperfiltration

Study Interventions

Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.

Drug:Furosemide first, then AcetazolamideTwo renal function studies will be performed: one before and after intravenous furosemide and the second before and after intravenous acetazolamide. Subjects will receive 300 mg of lithium carbonate at 22.00 the day before the renal function tests. A priming dose of inulin (50 mg/kg) and p-aminohippuric acid (8 mg/kg) will be administered and a 200-300 ml p.o water load will be given. Thereafter, inulin and p-aminohippuric acid will be infused continuously. After the first 60 minutes, 8 accurately timed urine collections of 30 to 40 minutes will be obtained by spontaneous voiding. After the first 4 timed urine collections, participants will receive intravenous furosemide 2 mg/5min or intravenous acetazolamide 5 mg/kg/5 min.Four other times urine collections will be performed thereafter.

Drug:Acetazolamide first, then FurosemideTwo renal function studies will be performed: one before and after intravenous acetazolamide and the second before and after intravenous furosemide. Subjects will receive 300 mg of lithium carbonate at 22.00 the day before the renal function tests.A priming dose of inulin (50 mg/kg) and p-aminohippuric acid (8 mg/kg) will be administered and a 200-300 ml p.o water load will be given. Thereafter, inulin and p-aminohippuric acid will be infused continuously. After the first 60 minutes, 8 accurately timed urine collections of 30 to 40 minutes will be obtained by spontaneous voiding. After the first 4 timed urine collections, participants will receive intravenous furosemide 2 mg/5min or intravenous acetazolamide 5 mg/kg/5 min.Four other times urine collections will be performed thereafter.

Study Arms

Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.

Furosemide first, then AcetazolamideTwo renal function studies will be performed: one before and after intravenous furosemide and the second before and after intravenous acetazolamide. Participants will receive intravenous furosemide 2 mg/5min or intravenous acetazolamide 5 mg/kg/5 min.

Acetazolamide first, then FurosemideTwo renal function studies will be performed: one before and after intravenous acetazolamide and the second before and after intravenous furosemide. Participants will receive intravenous furosemide 2 mg/5min or intravenous acetazolamide 5 mg/kg/5 min.

Study Status

Completed

Start Date: July 2010

Completed Date: May 2014

Phase: N/A

Type: Interventional

Design:

Primary Outcome: Change in GFR (ml/Min)

Secondary Outcome:

Study sponsors, principal investigator, and references

Principal Investigator: Boris Zingerman, MD

Lead Sponsor: Rabin Medical Center

Collaborator:

More information:https://clinicaltrials.gov/show/NCT01146288

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