Tominaga Naoto, Kida Keisuke, Inomata Takayuki, Sato Naoki, Izumi Tohru, Akashi Yoshihiro J, Shibagaki Yugo
Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan.
Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan.
Clin Exp Nephrol. 2018 Dec;22(6):1395-1403. doi: 10.1007/s10157-018-1603-1. Epub 2018 Jun 22.
Tolvaptan (TLV) is known to increase electrolyte-free water clearance. However, TLV actions on renal electrolytes including urine sodium (uNa) excretion and its consequences are less well understood. This subanalysis investigated the effect of add-on TLV compared to increased furosemide (FUR) on both electrolyte-free water and electrolyte clearance in patients with congestive heart failure (CHF) complicated by advanced chronic kidney disease (CKD).
The Kanagawa Aquaresis Investigators Trial of TLV on HF Patients with Renal Impairment (K-STAR) was a multicenter, open-labeled, randomized, and controlled prospective clinical study. Eighty-one Japanese patients with CHF and residual signs of congestion despite oral FUR treatment (≥ 40 mg/day) were recruited and randomly assigned to a 7-day add-on treatment with either ≤ 40 mg/day FUR or ≤ 15 mg/day TLV. Electrolyte-free water clearance, electrolyte osmolar clearance and electrolyte excretion were compared between the two groups before and after therapy.
The change (Δ) in electrolyte-free water clearance was significantly higher in the add-on TLV group than in the add-on FUR group. However, Δelectrolyte osmolar clearance was also higher in the add-on TLV group than in the increased FUR group. This was primarily because ΔuNa excretion was significantly higher in the add-on TLV group than in the increased FUR group, since Δurine potassium excretion was significantly lower in the add-on TLV group than in the increased FUR group.
Add-on TLV may increase both renal water and Na excretion in CHF patients with advanced CKD to a greater degree than increased FUR.
已知托伐普坦（TLV）可增加无电解质水清除率。然而，TLV对包括尿钠（uNa）排泄在内的肾脏电解质的作用及其后果尚不太清楚。本亚组分析研究了在合并晚期慢性肾脏病（CKD）的充血性心力衰竭（CHF）患者中，与增加呋塞米（FUR）剂量相比，加用TLV对无电解质水和电解质清除率的影响。
神奈川托伐普坦对心力衰竭合并肾功能损害患者的水清除作用研究（K-STAR）是一项多中心、开放标签、随机对照的前瞻性临床研究。招募了81例尽管接受口服FUR治疗（≥40mg/天）仍有充血残留体征的日本CHF患者，并将其随机分配至接受≤40mg/天FUR或≤15mg/天TLV的7天附加治疗组。比较两组治疗前后的无电解质水清除率、电解质渗透清除率和电解质排泄情况。
加用TLV组的无电解质水清除率变化（Δ）显著高于加用FUR组。然而，加用TLV组的Δ电解质渗透清除率也高于增加FUR剂量组。这主要是因为加用TLV组的ΔuNa排泄显著高于增加FUR剂量组，而加用TLV组的Δ尿钾排泄显著低于增加FUR剂量组。
在合并晚期CKD的CHF患者中，加用TLV可能比增加FUR剂量更大程度地增加肾脏水和钠的排泄。
