Komiyama Yasuyuki, Kurosaki Masayuki, Nakanishi Hiroyuki, Takahashi Yuka, Itakura Jun, Yasui Yutaka, Tamaki Nobuharu, Takada Hitomi, Higuchi Mayu, Gotou Tomoyuki, Kubota Youhei, Takaura Kenta, Hayashi Tsuguru, Oh Wann, Okada Mao, Enomoto Nobuyuki, Izumi Namiki
Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
PLoS One. 2017 Mar 31;12(3):e0174649. doi: 10.1371/journal.pone.0174649. eCollection 2017.
Tolvaptan is vasopressin type 2 receptor antagonist that inhibits water reabsorption. It is used in combination with standard diuretics to treat ascites unresponsive to standard diuretic therapy or hyponatremia because of liver cirrhosis. This study evaluated the effectiveness and safety of tolvaptan in clinical practice and aimed to determine the factors related to its effectiveness.
Tolvaptan was administered to 88 consecutive cirrhotic patients with ascites unresponsive to standard diuretic therapy. An effective treatment response was a ≥2% reduction in body weight on day 7. The association of patient pretreatment characteristics with therapeutic effects was analyzed.
Mean weight reduction on day 7 of tolvaptan therapy was -2.9% ± 3.2%, and treatment was effective in 52% of patients. Multivariate analysis revealed that spot urine Na/K ratio ≥2.5 at baseline was the only factor independently related to therapeutic effect, with an odds ratio of 7.85 (95% confidence interval 2.64-23.40, p = 0.0002). Weight reduction percentage on day 7 was -4.0% ± 2.8% in patients with spot urine Na/K ≥2.5, which was significantly greater than the 0.7% ± 2.7% loss in those with urine Na/K < 2.5 (p < 0.05). A spot urine Na/K ratio ≥2.5 had a sensitivity of 85% and specificity of 60% for predicting effective treatment. No adverse events of treatment led to treatment discontinuation.
Baseline spot urine Na/K was predictive of an effective response to tolvaptan therapy. It is simple to perform and readily available and might serve as an indicator of optimal timing of tolvaptan administration in patients with inadequate response to conventional Na diuretic therapy.
托伐普坦是一种血管加压素2型受体拮抗剂,可抑制水的重吸收。它与标准利尿剂联合使用,用于治疗对标准利尿治疗无反应的腹水或肝硬化引起的低钠血症。本研究评估了托伐普坦在临床实践中的有效性和安全性,并旨在确定与其有效性相关的因素。
对88例对标准利尿治疗无反应的肝硬化腹水患者连续给予托伐普坦治疗。有效的治疗反应是在第7天时体重减轻≥2%。分析患者治疗前特征与治疗效果之间的关联。
托伐普坦治疗第7天时平均体重减轻为-2.9%±3.2%,52%的患者治疗有效。多因素分析显示,基线时点尿钠/钾比值≥2.5是唯一与治疗效果独立相关的因素,比值比为7.85(95%置信区间2.64-23.40,p = 0.0002)。基线时点尿钠/钾≥2.5的患者第7天时体重减轻百分比为-4.0%±2.8%,显著高于尿钠/钾<2.5的患者的0.7%±2.7%的体重减轻幅度(p < 0.05)。基线时点尿钠/钾比值≥2.5预测有效治疗的敏感性为85%,特异性为60%。治疗的不良事件均未导致治疗中断。
基线时点尿钠/钾可预测托伐普坦治疗的有效反应。其操作简单且容易获得,可能作为传统钠利尿剂治疗反应不佳患者托伐普坦给药最佳时机的一个指标。