Comparative Safety and Effectiveness of Urea and Tolvaptan for the Management of Hyponatremia

Abstract

Background: The optimal management of euvolemic and hypervolemic hyponatremia remains controversial. The effectiveness of the vasopressin receptor antagonist tolvaptan on serum sodium normalization has been well described in the literature, although the associated risk of serum sodium overcorrection limits its use. Urea has been proposed as an alternative treatment option due to its milder serum sodium raising effects and adverse event profile. Objective: This study aimed to compare urea and tolvaptan for their serum sodium raising effects and potential for overcorrection. Methods: In a multicenter retrospective review, 46 hospitalized patients who received either urea or tolvaptan for the management of hyponatremia were evaluated for the rate of serum sodium normalization and overcorrection. Results: Mean serum sodium concentrations at baseline were 125.91 mEq/L and 123.83 mEq/L for patients treated with urea and tolvaptan, respectively. After 12 hours, tolvaptan was associated with a significantly higher rate of serum sodium increase compared with urea (5.05 mEq/L vs 1.10 mEq/L; P = .001). However, no statistically significant differences were observed in the mean change in serum sodium concentrations at 24 hours, 48 hours, or with the proportion of patients who reached a serum sodium concentration of 135 mEq/L. Overcorrection rates were significantly higher with tolvaptan compared with urea at 43% and 9%, respectively. Conclusion: The results of this study suggest that urea has a comparable effectiveness profile to tolvaptan for the management of hyponatremia with a significantly reduced risk of overcorrection.