Acute effects of lithium on the renal concentrating mechanism in a primate

Although chronic lithium therapy has been associated with a defect in the urinary concentrating mechanism, short-term renal effects of lithium have received little attention in the intact animal. Solute-free water reabsorption (T-cH2O) and free water clearance (CH2O) were measured in primates of the genus Galago under control conditions and while animals were receiving either 0.5 mmol/kg-h or 1.0 mmol/kg-h lithium chloride (135 mM) intravenously. CH2O was unchanged by lithium infusion (P greater than 0.10), whereas T-cH2O was significantly depressed at all levels of osmolal clearance (P smaller than 0.01). Spontaneous recovery of near-normal T-cH2O was documented in two animals within 1 wk following acute lithium infusion. In addition it was observed that lithium-induced depression of T-cH2O could be partially prevented by pretreatment with intravenous amiloride. These results suggest that alterations in the renal concentrating mechanism can occur rapidly following the onset of lithium administration. They also imply that impairment of the renal concentrating mechanism by lithium is due at least in part to antagonism of the action of vasopressin on the collecting duct.