Effect of Acetazolamide and Furosemide on Obesity-induced Glomerular Hyperfiltration
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ClinicalTrials.gov Identifier: NCT01146288 |
Recruitment Status :
Completed
First Posted : June 17, 2010
Results First Posted : June 4, 2015
Last Update Posted : June 4, 2015
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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 |
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Obesity-induced Hyperfiltration | Drug: Furosemide first, then Acetazolamide Drug: Acetazolamide first, then Furosemide | Not Applicable |

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 |

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

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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01146288
Israel | |
Rabin Medical Center | |
Petach Tikva, Israel |
Principal Investigator: | Boris Zingerman, MD | Rabin Medical Center |
Responsible Party: | boris zingerman, MD, Rabin Medical Center |
ClinicalTrials.gov Identifier: | NCT01146288 |
Other Study ID Numbers: |
ObesAceta 1 |
First Posted: | June 17, 2010 Key Record Dates |
Results First Posted: | June 4, 2015 |
Last Update Posted: | June 4, 2015 |
Last Verified: | June 2015 |
obesity acetazolamide furosemide |
Obesity Overnutrition Nutrition Disorders Overweight Body Weight 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 |