Treatment of Chronic Hyponatremia

Two vasopressin receptor antagonists (vaptans) are now available for treatment of euvolemic or hypervolemic hyponatremia in the United States. The Food and Drug Administration approved conivaptan, a combined V1a/V2 receptor antagonist, in December 2005. Although orally active, marketing was limited to a parenteral form intended for short-term hospital use because of concern for the drug's potency as a CYP3A4 inhibitor.1 Tolvaptan, a selective V2 receptor antagonist, was approved in May 2009. Like conivaptan, it has been shown in short-term studies to be effective in raising the serum sodium concentration in patients with diverse causes of hyponatremia.2 Until now, almost all of the published experience with vaptans in hyponatremia has come from studies of short duration, ranging from a single dose to 30 days of therapy.2,3 Longer term experience with conivaptan is convincing but anecdotal1; even a single study that used satavaptan to treat hyponatremia for up to 12 months had only 10 patients.4In this issue of JASN , important data on the long-term use of vaptan therapy in a much larger cohort are presented by Berl et al. 5 Termed Safety and sodium Assessment of Long-term Tolvaptan With hyponatremia: A year-long, open-label Trial to gain Experience under Real-world conditions (SALTWATER), it was an open-label extension of the earlier Study of Ascending Levels of Tolvaptan in Hyponatremia (SALT) in which SALT enrollees who previously received either tolvaptan or placebo for 30 days were given oral tolvaptan for up to 804 days.2 A total of 111 individuals participated in SALTWATER, and, over time, 64 discontinued the drug, 30 because of death or adverse reactions. The median time on …