Effect of Furosemide on Obesity-induced Glomerular Hyperfiltration

NCT00962286 | Terminated

• 1 other identifier: OBEFUR
• Study Type: interventional
• Target: 3
• 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 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.

Conditions

Obesity-induced Hyperfiltration

Keywords

Furosemide; obesity

Outcome Measures

Primary Outcomes (1)

• change in GFR

  3 days

Study Arms (1)

Furosemide, obesity, glomerular hyperfiltration

EXPERIMENTAL

Drug: Furosemide

Interventions

Furosemide DRUG

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.

Furosemide, obesity, glomerular hyperfiltration

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) will be included in the study.

You may not qualify if:

• Any of the following conditions:
• Heart failure
• Known allergy to furosemide, inulin or amino-hippurate
• Pharmacologic treatment for hypertension, cardiac disease, diabetes mellitus
• Treatment with corticosteroids or NSAID

Sponsors & Collaborators

• Rabin Medical Center: lead

Study Sites (1)

Rabin Medical Center

Petah Tikva, Israel

Location

Related Publications (1)

• 1. Chagnac A et al: Glomerular hemodynamics in severe obesity. Am J Physiol Renal Physiol. 2000;278(5):F817-22. 2. Chagnac A et al: The effects of weight loss on renal function in patients with severe obesity. J Am Soc Nephrol. 2003 Jun;14(6):1480-6. 3. Navar LG: Renal autoregulation: perspectives from whole kidney and single nephron studies. Am J Physiol. 1978 May;234(5):F357-70. 4. Deng A etal: Hemodynamics of early tubuloglomerular feedback resetting during reduced proximal reabsorption. Kidney Int. 2002 Dec;62(6):2136-43. 5. Dupont AG et al: Renal pharmacodynamic effects of torasemide and furosemide in normal man.Drug Res. 38(1) 1a 1998 172-175.

  BACKGROUND

MeSH Terms

Conditions

Obesity

Interventions

Furosemide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds

Study Officials

• Boris Zingerman, MD

  Rabin Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 18, 2009
• First Posted: August 19, 2009
• Study Start: September 1, 2009
• Primary Completion: May 1, 2010
• Study Completion: July 1, 2010
• Last Updated: August 4, 2011

Record last verified: 2009-08

Locations

IL (1)