AJP - Renal Physiology, Vol 258, Issue 4 1100-F1104, Copyright © 1990 by American Physiological Society
Does lithium clearance reflect distal delivery in humans? Analysis with furosemide infusion
E. J. Dorhout Mees, J. J. Beutler, W. H. Boer and H. A. Koomans
Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
Fractional excretion of lithium (FELi+) has been proposed as an index of
fluid delivery to the distal nephron. The increase in FELi+ after the "loop
diuretic" furosemide indicates that this postulate may not be valid unless
furosemide acts in the proximal tubules. We studied the effect of
furosemide (40 mg iv as bolus, followed by 20 mg/h infusion for 90 min) in
eight healthy male subjects during maximal water diuresis. Special care was
taken to exactly replace urinary losses. Furosemide greatly increased
fractional excretion of sodium, from 1.3 +/- 0.4 to 27.8 +/- 3.9%, and
water, from 14.2 +/- 1.7 to 38.2 +/- 3.7% (P less than 0.01). There was a
disproportionately large increase in FELi+ from 30.3 +/- 3.0 to 53.7 +/-
2.9% (P less than 0.01), whereas fractional excretion of some other alleged
proximal markers increased to a lesser extent. Lysine vasopressin, infused
at the end of the experiment (n = 7), caused only a small increase in urine
osmolality from 225 +/- 17 to 241 +/- 17 mosmol/kg (P less than 0.01),
indicating that medullary hyperosmolality had been largely abolished. The
most likely explanation of these results is that furosemide has a moderate
action in the proximal tubules, and at the same time inhibits preexistent
lithium absorption in Henle's loop. In addition, the large difference
between FELi+ and maximal urine flow remaining after furosemide suggests
that, despite the decreased medullary osmotic gradient, water backdiffusion
is unaltered by furosemide or that lithium concentration in the proximal
tubule is changed by furosemide.
