title: Acetazolamide and Hydrochlorothiazide Followed by Furosemide Versus Furosemide and Hydrochlorothiazide Followed by Furosemide for the Treatment of Adults With Nephrotic Edema: A Randomized Trial.
abstract: BACKGROUND
  Nephrotic edema is considered refractory if it does not respond to maximum or near-maximum doses of loop diuretics. This condition can be treated with loop diuretics and thiazides. However, animal studies show that the simultaneous downregulation of pendrin with acetazolamide and inhibition of the sodium-chloride cotransporter with hydrochlorothiazide generates significant diuresis, and furosemide administration following a pendrin inhibitor potentiates furosemide's diuretic effect. Therefore, we performed this study to compare the efficacy of acetazolamide and hydrochlorothiazide followed by furosemide versus furosemide and hydrochlorothiazide followed by furosemide for treatment of refractory nephrotic edema.
  
  
  METHODS
  Randomized, double-blind, 2-arm, parallel trial.
  
  
  METHODS
  20 patients with refractory nephrotic edema despite treatment with 80mg of furosemide daily and creatinine clearance > 60mL/min.
  
  
  METHODS
  Patients were randomly assigned to 2 groups: group 1 (n=10) received 250mg of acetazolamide and 50mg of hydrochlorothiazide daily and group 2 (n=10) received 40mg of furosemide and 50mg of hydrochlorothiazide daily for 1 week in phase 1. In phase 2, both groups received 40mg of furosemide daily for 2 weeks.
  
  
  RESULTS
  The primary outcome was absolute change in weight before and at the end of each phase.
  
  
  METHODS
  Weight and 24-hour urine volume at baseline and the end of each phase.
  
  
  RESULTS
  The mean weight decrease was of significantly larger magnitude in group 1 compared with group 2 at the end of phase 1 (-1.4±0.52 [SD] vs -0.65±0.41kg; P=0.001) and phase 2 (-1.6±0.84 vs -0.5±0.47kg; P=0.005). The increase in 24-hour urine volume was also significantly higher in group 1 at the end of phase 2.
  
  
  CONCLUSIONS
  Small sample size, short follow-up duration, and lack of serum bicarbonate and chloride measurement.
  
  
  CONCLUSIONS
  Acetazolamide and hydrochlorothiazide followed by furosemide is more effective than furosemide and hydrochlorothiazide followed by furosemide for the treatment of refractory nephrotic edema.
authors.affiliation: AJA University of Medical Sciences, Tehran, Iran; Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Mohammad Amin
authors.initials: MA
authors.lastname: Fallahzadeh
authors.affiliation: AJA University of Medical Sciences, Tehran, Iran. Electronic address: dr.dormanesh@yahoo.com.
authors.forename: Banafshe
authors.initials: B
authors.lastname: Dormanesh
authors.affiliation: Department of Internal Medicine, Baylor University Medical Center, Dallas, TX.
authors.forename: Mohammad Kazem
authors.initials: MK
authors.lastname: Fallahzadeh
authors.affiliation: Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Jamshid
authors.initials: J
authors.lastname: Roozbeh
authors.affiliation: Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Fallahzadeh
authors.affiliation: Shiraz Nephro-Urology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
authors.forename: Mohammad Mahdi
authors.initials: MM
authors.lastname: Sagheb
mesh_terms: D000086:Acetazolamide / Q000008:administration & dosage*; D000328:Adult; D004232:Diuretics / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004487:Edema / Q000188:drug therapy*; D005260:Female; D005665:Furosemide / Q000008:administration & dosage*; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage*; D007674:Kidney Diseases / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
chemical_list: D004232:Diuretics; D006852:Hydrochlorothiazide; D005665:Furosemide; D000086:Acetazolamide
keywords: Nephrotic syndrome; acetazolamide; diuretic; furosemide; hydrochlorothiazide; loop diuretics; nephrology; nephrotic edema; pendrin; randomized clinical trial; refractory edema; salt retention; sodium/chloride cotransporter (NCC); thiazides; urine volume; water retention; weight