title: Effect of Acetazolamide on Obesity-Induced Glomerular Hyperfiltration: A Randomized Controlled Trial.
abstract: OBJECTIVE
  Obesity is an important risk factor for the development of chronic kidney disease. One of the major factors involved in the pathogenesis of obesity-associated kidney disease is glomerular hyperfiltration. Increasing salt-delivery to the macula densa is expected to decrease glomerular filtration rate (GFR) by activating tubuloglomerular feedback. Acetazolamide, a carbonic anhydrase inhibitor which inhibits salt reabsorption in the proximal tubule, increases distal salt delivery. Its effects on obesity-related glomerular hyperfiltration have not previously been studied. The aim of this investigation was to evaluate whether administration of acetazolamide to obese non diabetic subjects reduces glomerular hyperfiltration.
  
  
  METHODS
  The study was performed using a randomized double-blind crossover design. Obese non-diabetic men with glomerular hyperfiltration were randomized to receive intravenously either acetazolamide or furosemide at equipotent doses. Twelve subjects received the allocated medications. Two weeks later, the same subjects received the drug which they had not received during the first study. Inulin clearance, p-aminohippuric acid clearance and fractional lithium excretion were measured before and after medications administration. The primary end point was a decrease in GFR, measured as inulin clearance.
  
  
  RESULTS
  GFR decreased by 21% following acetazolamide and did not decrease following furosemide. Renal vascular resistance increased by 12% following acetazolamide, while it remained unchanged following furosemide administration. Natriuresis increased similarly following acetazolamide and furosemide administration. Sodium balance was similar in both groups.
  
  
  CONCLUSIONS
  Intravenous acetazolamide decreased GFR in obese non-diabetic men with glomerular hyperfiltration. Furosemide, administered at equipotent dose, did not affect GFR, suggesting that acetazolamide reduced glomerular hyperfiltration by activating tubuloglomerular feedback.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01146288.
authors.affiliation: Department of Nephrology & Hypertension, Rabin Medical Center, Petah Tikva, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Boris
authors.initials: B
authors.lastname: Zingerman
authors.affiliation: Department of Nephrology & Hypertension, Rabin Medical Center, Petah Tikva, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Michal
authors.initials: M
authors.lastname: Herman-Edelstein
authors.affiliation: Department of Nephrology & Hypertension, Rabin Medical Center, Petah Tikva, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Arie
authors.initials: A
authors.lastname: Erman
authors.affiliation: Department of Nephrology & Hypertension, Rabin Medical Center, Petah Tikva, Israel.
authors.forename: Sarit
authors.initials: S
authors.lastname: Bar Sheshet Itach
authors.affiliation: Department of Nephrology & Hypertension, Rabin Medical Center, Petah Tikva, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yaacov
authors.initials: Y
authors.lastname: Ori
authors.affiliation: Department of Nephrology & Hypertension, Rabin Medical Center, Petah Tikva, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Benaya
authors.initials: B
authors.lastname: Rozen-Zvi
authors.affiliation: Department of Nephrology & Hypertension, Rabin Medical Center, Petah Tikva, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Uzi
authors.initials: U
authors.lastname: Gafter
authors.affiliation: Department of Nephrology & Hypertension, Rabin Medical Center, Petah Tikva, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Avry
authors.initials: A
authors.lastname: Chagnac
mesh_terms: D000086:Acetazolamide / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004232:Diuretics / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D004232:Diuretics; D005665:Furosemide; D000086:Acetazolamide