Effect of Acetazolamide and Furosemide on Obesity-induced Glomerular Hyperfiltration

NCT01146288 | Completed Results

• 1 other identifier: ObesAceta 1
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity-induced Hyperfiltration

Keywords

obesity; acetazolamide; furosemide

Outcome Measures

Primary Outcomes (2)

• Change in GFR (ml/Min)

  baseline and after diuretics administration

• Renal Vascular Resistance (mm Hg/[ml/Min])

  baseline and after diuretics administration

Study Arms (2)

Furosemide first, then Acetazolamide

EXPERIMENTAL

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

Acetazolamide first, then Furosemide

EXPERIMENTAL

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

Interventions

Furosemide first, then Acetazolamide DRUG

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.

Furosemide first, then Acetazolamide

Acetazolamide first, then Furosemide DRUG

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.

Acetazolamide first, then Furosemide

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Rabin Medical Center: lead

Study Sites (1)

Rabin Medical Center

Petah Tikva, Israel

Location

Related Publications (2)

• Conley MM, McFarlane CM, Johnson DW, Kelly JT, Campbell KL, MacLaughlin HL. Interventions for weight loss in people with chronic kidney disease who are overweight or obese. Cochrane Database Syst Rev. 2021 Mar 30;3(3):CD013119. doi: 10.1002/14651858.CD013119.pub2.

  PMID: 33782940 DERIVED

• 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.

  PMID: 26367377 DERIVED

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr Boris Zingerman
• Organization: Rabin Medical Center

borisz@clalit.org.il

Study Officials

• Boris Zingerman, MD

  Rabin Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: June 16, 2010
• First Posted: June 17, 2010
• Study Start: July 1, 2010
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: June 4, 2015
• Results First Posted: June 4, 2015

Record last verified: 2015-06

Locations

IL (1)