1. A study has been undertaken in six healthy male subjects to clarify whether post-proximal segments of the nephron contribute to the renal handling of lithium under conditions of maximal forced osmotic load diuresis and arginine vasopressin-induced antidiuresis. Increments in the fractional clearance of free water, as a measure of effect at the proximal tubule, were positively correlated with incremental changes in flow rate, factored for glomerular filtration rate (mean r = 0.80 ± 0.12, P < 0.001), and fractional excretion of lithium (mean r = 0.84 ± 0.06, P < 0.001). Changes in flow rate and fractional excretion of lithium were also closely correlated with one another (mean r = 0.81 ± 0.06, P < 0.001), and the mean slope of these regression lines was not significantly different from unity (1.18; 95% confidence interval 0.76–1.59). These results show that, under conditions of maximal hydration, mannitol-induced changes in proximal tubular function were closely correlated with induced changes in the fractional excretion of lithium.
2. Infusion of arginine vasopressin alone (0.5 m-units/min) caused a marked reduction in both fractional clearance of free water (10.7% ± 1.2% to −1.2% ± 0.2%, P < 0.001) and flow rate factored for glomerular filtration rate (14.0 ± 1.5 to 0.8 ± 0.2%; P < 0.001) while the fractional excretion of lithium showed only a small non-significant decrease (25.3% ± 2.0% to 23.3% ± 2.2%). A similar dissociation was noted between fluid and lithium excretion when arginine vasopressin was superimposed on mannitol infusion with reductions in the fractional clearance of free water (12.7% ± 1.0% to −0.9% ± 0.7%, P < 0.001) and flow rate (18.6% ± 1.5% to 5.7% ± 1.0%; P < 0.001), while the fractional excretion of lithium showed a significant increase (28.4% ± 1.7% to 33.1% ± 2.4%; P < 0.05). The lack of correlation between fluid and lithium excretion, in the presence of arginine vasopressin with or without mannitol, indicates that the late distal tubule and collecting duct have little or no significant capacity to reabsorb lithium.
3. These findings, taken as a whole, strengthen the view that renal tubular handling of lithium is primarily a proximal event.