Effectiveness of Urea and Tolvaptan in the Treatment of Hypotonic Hyponatremia

<b>Objective:</b> The objective of this study was to compare the effectiveness of urea and tolvaptan in the treatment of plasma sodium levels in patients with hypotonic hyponatremia. <b>Methods:</b> This was an observational, longitudinal, and retrospective study including all adult patients who received treatment with urea or tolvaptan for hypotonic hyponatremia from 1 April 2014 to 31 October 2023 at the Department of Internal Medicine, Virgen del Rocío University Hospital, Seville, Spain. <b>Results:</b> Forty-seven (55.3%) patients received urea and 38 (44.7%) tolvaptan. The drugs were prescribed for the treatment of syndrome of inappropriate antidiuresis (SIAD) in 59 (69.4%) patients. The mean blood sodium level at the start of treatment was 123.5 ± 6.2 mEq/L. Overall, 61.7% and 63.2% of patients treated with urea and tolvaptan, respectively, achieved a normal blood sodium level (<i>p</i> = 0.89), although the time to have their sodium levels corrected differed between both groups: 41.7 ± 76 days with urea and 21 ± 23.9 days with tolvaptan (<i>p</i> = 0.038). The following were significant in the multivariate study: Initial sodium value (<i>p</i> = 0.037), absolute sodium improvement (<i>p</i> = 0.041), and percentage sodium improvement (<i>p</i> = 0.033). Among patients with SIAD, 69.5% achieved a normal sodium level; this figure was 45.5% for patients with heart failure. Three patients reported side adverse events in the urea group and none in the tolvaptan group. <b>Conclusions:</b> Our data, reflecting real-world practice and follow-up of patients with hypotonic hyponatremia, suggest that both urea and tolvaptan are safe, well-tolerated, and have a similar effectiveness in correcting blood sodium levels in patients with hypotonic hyponatremia, overall and secondary to SIAD, though treatment with tolvaptan achieved this goal earlier than urea.