title: Intratubular albumin blunts the response to furosemide-A mechanism for diuretic resistance in the nephrotic syndrome.
abstract: An attenuated response to loop diuretics is a frequent observation in the nephrotic syndrome. To determine if the presence of albumin in renal tubular fluid attenuates diuretic response in normal rats, in vivo loop segment microperfusion was performed in normal rats at 20 nl/min with perfusates containing 6.0 microM furosemide in the presence and absence of 3.8 microM albumin. Compared to loop segments perfused without diuretic (control), furosemide reduced (P less than .001) fractional chloride uptake from 56 +/- 2 to 34 +/- 2%. After addition of albumin to furosemide perfusate, fractional loop chloride reabsorption was 45 +/- 1%; a value greater (P less than .01) than that observed in furosemide perfused loop segments, but less (P less than .05) than that observed in control loop segments. Albumin added to perfusate in the absence of furosemide had no effect on fractional loop segment chloride uptake. Addition of 1.7 microM immunoglobulin G to furosemide perfusate failed to attenuate furosemide response. Absolute loop segment chloride reabsorption demonstrated a similar pattern. Tubule fluid perfusion rates determined in vivo and loop segment fluid reabsorption were equivalent in all groups. Thus, albumin in renal tubule fluid attenuates the effect of furosemide on loop segment chloride reabsorption in the rat. This blunted response presumably occurs because of a reduction in the amount of pharmacologically active drug due to albumin-furosemide binding. Consequently, albumin-furosemide binding in the renal tubule may contribute to the diuretic resistance in nephrotic syndrome.
authors.affiliation: Department of Medicine, University of Mississippi Medical Center, Jackson.
authors.forename: K A
authors.initials: KA
authors.lastname: Kirchner
authors.forename: J R
authors.initials: JR
authors.lastname: Voelker
authors.forename: D C
authors.initials: DC
authors.lastname: Brater
mesh_terms: D000042:Absorption; D000418:Albumins / Q000494:pharmacology*; D000818:Animals; D002712:Chlorides / Q000493:pharmacokinetics*; D005665:Furosemide / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000494:pharmacology; D007684:Kidney Tubules / Q000187:drug effects*; D008138:Loop of Henle / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000418:Albumins; D002712:Chlorides; D007074:Immunoglobulin G; D005665:Furosemide