A retrospective study of tolvaptan versus urea for the second-line treatment of the syndrome of inappropriate antidiuresis — ASN Events
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A retrospective study of tolvaptan versus urea for the second-line treatment of the syndrome of inappropriate antidiuresis (#304)

Rose Lin 1 2 , Matthew Morton 2 , Mathi Grossmann 1 , Anthony Russell 2 , Annabelle Warren 1 2
  1. Department of Endocrinology, Austin Health, Heidelberg, VIC, Australia
  2. Department of Endocrinology, Bayside Health, the Alfred, Melbourne, VIC, Australia

Background: Initial treatment of hyponatraemia due to the syndrome of inappropriate antidiuresis (SIAD) is fluid restriction and correction of underlying causes (1, 2). Refractory cases may require second-line treatment with urea or tolvaptan (3). The relative efficacy and safety of these treatments in raising plasma sodium concentration (pNa) is unclear.

Objective: Assess the efficacy and safety of tolvaptan versus urea in hospitalised patients with hyponatraemia.

Methods: Single-centre retrospective cohort study was conducted at Alfred Health, a tertiary hospital in Melbourne, Australia. Adults with SIAD treated with tolvaptan or urea from November 2017 to October 2024 were included. Main outcomes included pNa change at 24 and 72 hours, whether pNa normalised, and rates of overcorrection (pNa rise >10mmol/L in 24 hours).

Results: Of 126 eligible patients, 32 received tolvaptan and 94 received urea. Baseline mean pNa was 122.7 mmol/L vs 125.1 mmol/L respectively (p=0.03). At 24 and 72 hours post-treatment initiation, mean pNa rise in the tolvaptan group was 5.7 and 6.7 mmol/L, compared with 1.9 mmol/L and 5.9 mmol/L in the urea group respectively (p<0.001 at 24 hours, p=0.39 at 72 hours). Overcorrection occurred in five patients (15.6%) in the tolvaptan group compared with two (2.1%) in the urea group (p=0.004).

Conclusion: Both tolvaptan and urea can be used safely and effectively as a second-line therapy for SIAD, with appropriate monitoring. Tolvaptan was more efficacious in the first 24 hours but had a higher risk of overcorrection compared with urea. Prospective randomised trials are required to assess their comparative efficacy and safety further.

  1. 1. Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. European Journal of Endocrinology. 2014;170(3):G1-47.
  2. 2. Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH, et al. Diagnosis, evaluation, and treatment of hyponatremia: Expert panel recommendations. The American Journal of Medicine. 2013;126(10 Suppl 1):S1-42.
  3. 3. Warren AM, Grossmann M, Christ-Crain M, Russell N. Syndrome of inappropriate antidiuresis: From pathophysiology to management. Endocrine Reviews. 2023;44(5):819-61.