title: Urinary protein binding does not affect response to furosemide in patients with nephrotic syndrome.
abstract: Response to loop diuretics in patients with nephrotic syndrome (NS) is subnormal. Studies in animal models of NS have suggested that binding of diuretic to urinary albumin is one of the mechanisms that may be operative in this diuretic resistance. To explore this hypothesis, 12 patients with NS were studied to determine whether displacement from urinary protein binding with sulfisoxazole would restore response to 120 mg of furosemide. The study was stopped after treating seven patients because it was clear that sulfizoxazole had no effect. Sodium excretion (mean +/- SD) from furosemide alone was 239 +/- 90 versus 240 +/- 115 mEq/8 h with sulfisoxazole. Sulfisoxazole had modest effects on serum pharmacokinetics of furosemide but had no effect on either the time course of furosemide urinary excretion or overall amount excreted: 49 +/- 15 mg versus 54 +/- 12 mg for furosemide alone and furosemide plus sulfisoxazole, respectively. It is concluded that urinary protein binding of loop diuretics is not a major mechanism for the diuretic resistance of NS. In turn, strategies aimed at displacing such binding are unlikely to be clinically helpful.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Agarwal
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Gorski
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Sundblad
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: D Craig
authors.initials: DC
authors.lastname: Brater
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use* / Q000652:urine*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004232:Diuretics / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000652:urine; D005260:Female; D005665:Furosemide / Q000493:pharmacokinetics / Q000627:therapeutic use* / Q000652:urine; D006801:Humans; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000652:urine*; D011485:Protein Binding; D012964:Sodium / Q000652:urine; D013444:Sulfisoxazole / Q000627:therapeutic use* / Q000652:urine*; D014556:Urine / Q000737:chemistry
chemical_list: D000890:Anti-Infective Agents; D004232:Diuretics; D013444:Sulfisoxazole; D005665:Furosemide; D012964:Sodium