Amelioration of polyuria by amiloride in patients receiving long-term lithium therapy

Vasopressin-resistant diabetes insipidus is a common side effect of the treatment of affective disorders with lithium. We studied the effect of amiloride on lithium-induced polyuria in nine such patients receiving maintenance lithium therapy who had a vasopressin-resistant defect in urinary concentrating ability. After a mean (+/- S.E.) of 24 +/- 6 days of amiloride administration, the urine volume fell (from 4.7 +/- 0.6 to 3.1 +/- 0.3 liters per 24 hours; P less than 0.005), and the urine osmolality increased (from 228 +/- 35 to 331 +/- 34 mOsm per kilogram of H2O; P less than 0.001). The decrease in urine output was sustained during six months of observation in the absence of any significant change in plasma levels of lithium, potassium, or bicarbonate; urinary excretion of sodium or lithium; or creatinine clearance. Amiloride administration was also associated with a significant increase in urine osmolality (from 575 +/- 54 to 699 +/- 48 mOsm per kilogram of H2O; P less than 0.005) measured after fluid deprivation and the injection of exogenous vasopressin. We conclude that amiloride mitigates lithium-induced polyuria, at least partly, by blunting the inhibitory effect of lithium on water transport in the renal collecting tubule. Thus, amiloride may provide a specific therapy for polyuria in lithium-treated patients while obviating the need for potassium supplementation in the treatment of this kind of polyuria.