Serum and urine responses to the aquaretic agent tolvaptan in hospitalized hyponatremic patients

Abstract

Tolvaptan, an oral, selective arginine vasopressin (AVP) V2 receptor antagonist has been approved for the treatment of euvolemic and hypervolemic hyponatremia in the United States. This report summarizes our center's experience with thirteen patients treated for hyponatremia with one 15-mg dose of tolvaptan. The patients had euvolemic or hypervolemic hyponatremia with decreased serum osmolality and serum sodium (SNa) levels less than 129 mEq/L. Eight patients had a diagnosis of the syndrome of inappropriate antidiuretic hormone (SIADH), and five patients had a diagnosis of congestive heart failure (CHF). Results revealed an increase in SNa in all patients from 122.5 ± 4.2 to 128.9 ± 4.1 mEq/L (P < 0.05). The mean increase in SNa of 6.4 mEq/L (range 2-10 mEq/L) 24 h post-tolvaptan was not different in the two groups of patients, but SIADH patients had higher pre and post-tolvaptan SNa levels than CHF patients. Urine osmolalities (UOsm) decreased in all patients, and the patients with SIADH had significantly higher baseline UOsm and a larger decrease in UOsm 12 h post-tolvaptan administration when compared with the CHF patients. AVP levels did not change post-tolvaptan administration. However, the magnitude of increase in SNa levels was inversely related to pretolvaptan AVP levels in the SIADH subgroup (r = -0.7, P = 0.01). Three SIADH patients received small amounts of D5W to attenuate changes in SNa. No significant changes in mean arterial pressure, serum potassium, serum glucose, and blood urea nitrogen or serum creatinine were observed. The data show that tolvaptan is effective for the treatment of hyponatremia and may produce differing responses in disparate patient groups.