Urinary thiamine excretion in the rat: Effects of furosemide, other diuretics, and volume load

Long-term furosemide therapy is associated with increased urinary loss of t hiamine. To examine the mechanism of furosemide-induced urinary thiamine lo ss, we measured urinary excretion of thiamine in rats in response to increa sing doses of furosemide, acetazolamide, chlorothiazide, amiloride, mannito l, and extracellular fluid (ECF) volume loading by saline infusion. All ani mals were in normal thiamine balance as reflected by a thiamine pyrophospha te effect (TPPE) of 2.25% +/- 0.60% (mean +/- SEM), and all had normal rena l function. Urinary flow increased in response to diuretic administration i n a dose-dependent manner, reaching (mean) peak urinary flow rates of 283 t o 402 mu L/min. Fractional excretion of sodium (FEN,) exhibited the same pa ttern, reaching peak values of 12.3% to 23.2%. Urinary thiamine excretion i ncreased in proportion to the incremental doses of diuretic agents, reachin g (mean) maximal values of 7.44 to 9.34 pmol/min, with no significant diffe rence (P = .11) between the various diuretics tested nor in response to sal ine loading. None of the diuretics tested differed in the effect on thiamin e excretion, which was clearly flow dependent and only partially related to fractional sodium excretion. Urinary flow rate, being the single significa nt predictor, explained 78% (R-2 = 0.78) of the variability in thiamine exc retion rates. These findings indicate that urinary thiamine loss is caused by a nonspecific, flow-dependent mechanism common to all of the diuretics t ested.