Efficacy and Tolerance of Urea Compared with Vaptans for Long-Term Treatment of Patients with SIADH

Background and objectives Vaptans (vasopressin V-2-receptor antagonists) are a new approach for the treatment of hyponatremia. However, their indications remain to be determined, and their benefit compared with that of the usual treatments for the syndrome of inappropriate antidiuretic hormone secretion (SIADH) have not been evaluated. This prospective, long-term study compared the efficacy, tolerability, and safety of two oral vaptans with those of oral urea in patients with SIADH. Design, setting, participants, & measurements Patients with chronic SIADH of various origins were treated first with vaptans for 1 year. After an 8-day holiday period, they received oral urea for an additional 1-year follow-up. Serum sodium was measured every 2 months, and drug doses were adjusted accordingly. Results Thirteen participants were initially included in the study (serum sodium, 125 +/- 3 mEq/L); 12 completed the 2-year treatment period. Treatment with vaptans (satavaptan, 5-50 mg/d, n=10; tolvaptan, 30-60 mg/day, n=2) increased natremia (serum sodium, 135 +/- 3 mEq/L) during the 1-year vaptan period without escape. Hyponatremia recurred in the 12 participants when vaptans were stopped (holiday period). Urea improved the natremia with the same efficacy (serum sodium, 135 +/- 2 mEq/L) as vaptans during the 1-year urea treatment period. One participant treated with tolvaptan withdrew from the study early because of excessive thirst. Another patient receiving urea developed hypernatremia without complications. Conclusions Urea has efficacy similar to that of vaptans for treatment of chronic SIADH. Tolerance is generally good for both agents. Clin J Am Soc Nephrol 7: 742-747, 2012. doi: 10.2215/CJN.06990711