Abstract
Tolvaptan is an effective treatment for hyponatremia, but concerns about hepatotoxicity, mainly from high-dose, long-term use in autosomal dominant polycystic kidney disease, have limited its widespread application. This study aimed to assess the efficacy and hepatic safety of short-term, low-dose tolvaptan in hospitalized patients with severe hyponatremia, in comparison with 3% hypertonic saline. We retrospectively evaluated 236 hospitalized adults with severe hyponatremia (serum sodium < 125 mEq/L). A total of 118 patients received oral tolvaptan (15 mg/day for ≥ 4 days), while 118 received only 3% hypertonic saline. Changes in serum sodium, potassium, blood urea nitrogen, creatinine, and liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], bilirubin) were analyzed over time. Liver enzymes were evaluated separately in subgroups with normal and elevated baseline values. Both treatment groups exhibited significant increases in serum sodium over time (P < .001). At the 24th and 72nd hours, sodium levels were higher in the tolvaptan group (P = .042). Among patients with normal liver enzymes at baseline, transient fluctuations in AST and ALT were observed, without clinically significant elevations. In those with elevated baseline values, AST and bilirubin levels showed improvement, while ALT remained stable. No cases of clinically apparent hepatotoxicity were reported. Short-term, low-dose tolvaptan is effective in correcting severe hyponatremia and does not appear to adversely affect liver function, even in patients with preexisting liver enzyme elevations. These findings support its use as a safe and practical therapeutic alternative in select hospitalized patients. Further prospective studies are warranted to confirm these observations.