Effect of an acute oral lithium intake on urinary Aquaporin-2 in healthy humans with and without simultaneous stimulation with hypertonic saline infusion

Abstract

Objective: Animal experiments have shown that lithium interferes with the formation of Aquaporin‐2 in the distal renal tubuli. The effect of lithium on formation of renal water channels has not been studied in healthy humans. The aim of this study was to test the hypotheses that a single oral dose of lithium will reduce the formation of water channels both with and without stimulation with hypertonic saline infusion, and that this effect can be detected by measurement of urinary excretion of Aquaporin‐2 (u‐AQP2). Methods: In healthy subjects, Study 1 (n=11) and Study 2 (n=12), urine was collected in 6 and 7 periods between 08.00 and 14.00, respectively, and blood samples were drawn at 30‐ to 60‐min intervals. The study medication was given at 09.00; u‐AQP2 was determined by radioimmunoassay. Results: In Study 1 neither u‐AQP2 nor urinary output were significantly changed by lithium. In Study 2, u‐AQP2 was increased by hypertonic saline infusion in parallel with an increase in arginine vasopressin. At the end of the study, u‐AQP2 was increased by 30% with placebo but only by 13% with the 600 mg lithium dose, and urinary output was significantly higher after 600 mg lithium than after placebo and 300 mg lithium. Conclusions: U‐AQP2 was not significantly changed after a single oral dose of lithium. The antidiuretic response to hypertonic saline infusion was reduced when lithium was given. It is suggested that lithium increases urinary output by inhibiting trafficking of renal water channels in healthy humans.