title: Urinary thiamine excretion in the rat: effects of furosemide, other diuretics, and volume load.
abstract: Long-term furosemide therapy is associated with increased urinary loss of thiamine. To examine the mechanism of furosemide-induced urinary thiamine loss, we measured urinary excretion of thiamine in rats in response to increasing doses of furosemide, acetazolamide, chlorothiazide, amiloride, mannitol, and extracellular fluid (ECF) volume loading by saline infusion. All animals were in normal thiamine balance as reflected by a thiamine pyrophosphate effect (TPPE) of 2.25% +/- 0.60% (mean +/- SEM), and all had normal renal function. Urinary flow increased in response to diuretic administration in a dose-dependent manner, reaching (mean) peak urinary flow rates of 283 to 402 microL/min. Fractional excretion of sodium (FE(Na)) exhibited the same pattern, reaching peak values of 12.3% to 23.2%. Urinary thiamine excretion increased in proportion to the incremental doses of diuretic agents, reaching (mean) maximal values of 7.44 to 9.34 pmol/min, with no significant difference (P = .11) between the various diuretics tested nor in response to saline loading. None of the diuretics tested differed in the effect on thiamine excretion, which was clearly flow dependent and only partially related to fractional sodium excretion. Urinary flow rate, being the single significant predictor, explained 78% (R2 = 0.78) of the variability in thiamine excretion rates. These findings indicate that urinary thiamine loss is caused by a nonspecific, flow-dependent mechanism common to all of the diuretics tested.
authors.affiliation: Department of Medicine, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Lubetsky
authors.forename: J
authors.initials: J
authors.lastname: Winaver
authors.forename: H
authors.initials: H
authors.lastname: Seligmann
authors.forename: D
authors.initials: D
authors.lastname: Olchovsky
authors.forename: S
authors.initials: S
authors.lastname: Almog
authors.forename: H
authors.initials: H
authors.lastname: Halkin
authors.forename: D
authors.initials: D
authors.lastname: Ezra
mesh_terms: D000818:Animals; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000008:administration & dosage / Q000633:toxicity*; D005665:Furosemide / Q000008:administration & dosage / Q000633:toxicity*; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000008:administration & dosage; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013831:Thiamine / Q000652:urine*; D013832:Thiamine Deficiency / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism
chemical_list: D004232:Diuretics; D008353:Mannitol; D005665:Furosemide; D013831:Thiamine