Urea vs. tolvaptan for hospitalized patients with SIADH

RATIONALE: Hyponatremia is the most common electrolyte disorder found in hospitalized patients and is associated with an increased mortality. Urea has been proposed as an alternative to vasopressin receptor antagonists (VRA) in the treatment of SIAD though comparative data are scarce. The aim was to evaluate the effectiveness and safety of urea compared with tolvaptan for treating SIAD in hospitalized patients. METHODS: Retrospective cohort study of adult inpatients with SIAD (serum sodium <130 mmol/L) treated with either urea or tolvaptan at a single institution between January 2015 and December 2023. Inverse probability of treatment weighting adjusted for confounders. Primary outcome was the proportion of patients achieving a serum sodium of >130 mmol/L. Secondary outcomes included time to treatment goal, serum sodium changes at 24, 48, and 72 hours, proportion of overcorrection (>10 mmol/L per 24 hours) and resource utilization. RESULTS: Of 537 patients, 463 received urea (median age 78 years; 57% female; baseline serum sodium 124.2 mmol/L, mean starting dose: 26 ± 6.1 g daily) and 74 received tolvaptan (68 years; 56% female; 123.6 mmol/L, mean starting dose 12.9 ± 6.5 mg daily). Similar proportions reached a serum sodium >130 mmol/L (79.7% vs 78.0%, P = 0.986). Time to target showed a trend favoring tolvaptan (2 (IQR 1-4) vs 3 (IQR 2-5) days, P = 0.077). Tolvaptan produced faster sodium increases at 48 hours (8.3 (IQR 4.4-12.0) vs. 5.6 (IQR 2.9-9.0) mmol/L), P = 0.001) but also more overcorrections (>10 mmol/L per 24 hours: 10.8% vs 3.2%, P = 0.011). Treatment duration was longer with tolvaptan (7 (IQR 4-11) vs 5 (IQR 3-8) days, P = 0.001), with substantially higher costs (€468 vs €12, P < 0.001). CONCLUSIONS: Urea may have a comparable effectiveness to tolvaptan with similar success rates but fewer overcorrections and substantially lower costs. These findings support urea as a safe and cost-effective first-line treatment option for appropriate patients with SIAD.