Effect of Acetazolamide and Furosemide on Obesity-induced Glomerular Hyperfiltration

• Status: Completed
• Trial end date: 2014-05-01
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Rabin Medical Center
• Treatments: Acetazolamide; Furosemide; Lithium Carbonate

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