Lithium clearance in man: Effects of dietary salt intake, acute changes in extracellular fluid volume, amiloride and frusemide

Abstract

1. The effects of amiloride and frusemide on lithium clearance were studied during changes in dietary sodium chloride intake and during infusion of 0.9% NaCl in normal human volunteers. 2. Lithium and fractional lithium clearances were less on the low than on the high salt diet. Values for the medium salt diet were intermediate. Acute extracellular fluid volume expansion with 0.9% NaCl infusion and extracellular fluid volume contraction 3-4 h after intravenous frusemide caused lithium and fractional lithium clearances to increase and decrease respectively. 3. Amiloride caused small changes in lithium and fractional lithium clearances on a low salt diet, but was without effect when salt intake was medium or high. 4. Increases in lithium clearance occurred immediately after frusemide irrespective of dietary salt intake and in subjects infused with 0.9% NaCl. Only in salt-depleted subjects did frusemide cause a substantial increase in fractional lithium clearance. Changes induced under other circumstances were small. 5. It is concluded that the lithium clearance method for assessment of proximal tubule salt and water reabsorption can be used with some degree of confidence in certain circumstances (medium and high salt intake as well as in acute volume expansion) but may not be reliable when dietary salt intake is low.

Abnormal renal responses to calcium entry blockade in normotensive offspring of hypertensive parents.

“…15 However, Weder 15 measured lithium excretion in subjects with a mean basal fractional sodium excretion of around 0.6%. Since some lithium reabsorption has been demonstrated to occur beyond the proximal tubule in sodium-restricted animals 17 -18 and in humans, 19 lithium excretion may be of limited importance in estimating proximal tubular reabsorption under such experimental conditions. The high sodium intake used in the present study, which ensured a basal fractional sodium excretion of 1.2%, should prevent this confounding factor in estimating proximal tubular reabsorption.…”

Effects of acute beta‐adrenoceptor blockade with metoprolol on the renal response to dopamine in normal humans.

“…The use of lithium clearance as an index of proximal tubular outflow to the thin descending limp of Henle relies on the assumptions that lithium is reabsorbed in parallel with sodium and water in the proximal tubules, but not reabsorbed or secreted in the distal tubules [9]. Based on direct measurements by in vivo micropuncture techniques in rats [10,17] and indirect evidence obtained by diuretic drug effect studies in man [9,18,19], it is now generally agreed that the lithium clearance method provides a reasonable, whole kidney' measure of end-proximal volume delivery in man under normal physiological conditions [20]. Recently, the lithium test doses used in clearance studies similar to the present one were shown to increase baseline sodium excretion on the study day, but the subsequent response to dopamine remained unchanged [21].…”

Interactions Between Furosemide and the Renal Sympathetic Nerves

“…Later studies have consistently shown that loop diuretics increase CL, and FEL, and the lack of effect of loop diuretics on CLI in the study by Thomsen & Schou (1968) has been ascribed to the long urine collection period (7 hours). Thus, furosemide produces substantial increases in CLI and FEL, in both rats (Steele et al 1976;Thomsen & Leyssac 1986a;Christensen et al 1986Christensen et al , 1987Kirchner 1987;Shirley et al 1992;Fransen et al 1993; IV, VI) and humans (Steele et al 1975;Atherton et al 1987Atherton et al & 1988Rombola et al 1987;Sjostrom 1988;Andreasen et al 1989;Shalmi et a1 1990a;Beutler et al 1990). Similar increases in CLI and FEL, have been reported with bumetanide Staalsen & Steiness 1990;Unwin et al 1994), ethacrynic acid , and the stereoisomer 1-ozolinone (Shalmi et al 1990b).…”

“…Fransen et al (1992) have confirmed these findings and by free-flow micropuncture technique they demonstrated that amiloride inhibits Li reabsorption at a site beyond the early distal tubule in Na depleted rats. There are no evidence for amiloride-sensitive Li reabsorption during Na restriction in humans (Atherton et al 1987;Boer et al 1988;Bruun et al 1989).…”