Effect of Acetazolamide and Furosemide on Obesity-induced Glomerular Hyperfiltration

• ClinicalTrials.gov Identifier: NCT01146288
• Recruitment Status: Completed
• First Posted: June 17, 2010
• Results First Posted: June 4, 2015
• Last Update Posted: June 4, 2015
• Sponsor: Rabin Medical Center
• Information provided by (Responsible Party): boris zingerman, Rabin Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Obesity-induced Hyperfiltration	Drug: Furosemide first, then Acetazolamide; Drug: Acetazolamide first, then Furosemide	Not Applicable

  Show Detailed Description

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 13 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect of Acetazolamide and Furosemide on Obesity-induced Glomerular Hyperfiltration
• Study Start Date: July 2010
• Actual Primary Completion Date: May 2014
• Actual Study Completion Date: May 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Furosemide first, then Acetazolamide; Two 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.	Drug: Furosemide first, then Acetazolamide; Two 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.
Experimental: Acetazolamide first, then Furosemide; Two 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.	Drug: Acetazolamide first, then Furosemide; Two 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.

Outcome Measures

Primary Outcome Measures :

1. Change in GFR (ml/Min) [ Time Frame: baseline and after diuretics administration ]
2. Renal Vascular Resistance (mm Hg/[ml/Min]) [ Time Frame: baseline and after diuretics administration ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Israel

Rabin Medical Center

Petach Tikva, Israel

Sponsors and Collaborators

Rabin Medical Center

Investigators

• Principal Investigator: Boris Zingerman, MD; Rabin Medical Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Zingerman B, Herman-Edelstein M, Erman A, Bar Sheshet Itach S, Ori Y, Rozen-Zvi B, Gafter U, Chagnac A. Effect of Acetazolamide on Obesity-Induced Glomerular Hyperfiltration: A Randomized Controlled Trial. PLoS One. 2015 Sep 14;10(9):e0137163. doi: 10.1371/journal.pone.0137163. eCollection 2015.

• Responsible Party: boris zingerman, MD, Rabin Medical Center
• ClinicalTrials.gov Identifier: NCT01146288 History of Changes
• Other Study ID Numbers: ObesAceta 1
• First Posted: June 17, 2010
• Results First Posted: June 4, 2015
• Last Update Posted: June 4, 2015
• Last Verified: June 2015

Keywords provided by boris zingerman, Rabin Medical Center:

obesity; acetazolamide; furosemide

Additional relevant MeSH terms:

Obesity; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Signs and Symptoms; Furosemide; Acetazolamide; Diuretics; Natriuretic Agents; Physiological Effects of Drugs; Sodium Potassium Chloride Symporter Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Anticonvulsants; Carbonic Anhydrase Inhibitors; Enzyme Inhibitors