Close correlation between urinary sodium excretion and response to tolvaptan in liver cirrhosis patients with ascites

Abstract

Aim: To assess the correlation between response to tolvaptan and treatment-related factors in liver cirrhosis patients.Methods: This single-center retrospective study was carried out at Shonan Kamakura General Hospital in Kanagawa, Japan, between October 2013 and September 2015. Forty-three liver cirrhosis patients (mean age, 65.7 years) with insufficient responses to conventional diuretics for at least 7 days were enrolled. All patients received oral tolvaptan (7.5 mg/day for 7 days) and guideline-directed medical therapy including sodium intake restrictions. A responder to tolvaptan was defined as a patient having a ≥2-kg decrease in body weight 1 week after commencing drug treatment, and a non-responder was defined as a patient not losing ≥2 kg in body weight 1 week after commencing treatment. We investigated the correlation of change in body weight for 1 week after drug administration compared to baseline clinical characteristics. Results:The mean body weight change from the baseline on the final dosing day was À2.47 ± 3.34 kg (P < 0.0001). There were 20 (46.5%) responders to tolvaptan. Urinary sodium and volume excretion was higher in responders than in non-responders (108.2 ± 70.5 vs 42.6 ± 36.7, P = 0.0003; 1462.8 ± 625.7 vs 960.9 ± 600.6, P = 0.0073). Logistic regression analyses for responders to tolvaptan were carried out, and independent correlation of the responders was urinary sodium excretion (P = 0.0114; hazard ratio, 0.9418; 95% confidence interval, 0.8768À0.9896) in the multivariate analyses. Conclusion:In decompensated liver cirrhosis patients, urinary excretion sodium showed good correlation with tolvaptan response.

Survival Benefit of Tolvaptan for Refractory Ascites in Patients with Advanced Cirrhosis

“…Urinary Na/K ratio has been reported to be an indicator of daily sodium excretion [29, 30] and an indirect indicator of mineral corticoid activity [31, 32]. In agreement with a previous study [18], the present study showed that spot urinary sodium may be predictive of response to tolvaptan. Urinary sodium can be evaluated easily and reproducibly.…”

“…Serum creatinine levels at 4, 8, and 12 weeks (±1 week at each point) after tolvaptan administration were obtained. Patients showing a ≥–2 kg reduction in body weight within 1 week of tolvaptan administration were defined as responders, with other patients were defined as non-responders [18]. The median observation period was 124 days (range 4–1,058 days).…”

“…In contrast, less is known about factors predictive of the long-term effectiveness of tolvaptan [13-18]. Renal function was thought to predict tolvaptan effectiveness in a real world clinical setting [19].…”

“…Renal function was thought to predict tolvaptan effectiveness in a real world clinical setting [19]. Recently urinary sodium excretion, which correlates daily sodium and free water excretion, was reported to be a simple predictive indicator of tolvaptan effectiveness [17, 18]. This was regarded as theoretically reasonable, because tolvaptan inhibits water reabsorption and promotes free water excretion [20].…”

Predictors of the Response to Tolvaptan Therapy and Its Effect on Prognosis in Cirrhotic Patients with Ascites

“…Free water clearance [14], aquaporin-2/AVP [15], and urinary Na excretion [16] were reported to be predictors of a tolvaptan response in patients with cirrhosis. The combination of BUN/Cr and urine Na/K ratios was the first reported predictor of a tolvaptan response.…”