Naoto Tominaga1, Keisuke Kida2, Takayuki Inomata3, Naoki Sato4, Tohru Izumi3, Yoshihiro J Akashi2, Yugo Shibagaki5. 1. 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. tominaga1213@kbd.biglobe.ne.jp. 2. Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan. 3. Department of Cardiovascular Medicine, Kitasato University School of Medicine, 1-15-1, Kitasato, Minami-Ku, Sagamihara, Kanagawa, 252-0374, Japan. 4. Division of Cardiology, Department of Internal Medicine, Nippon Medical School Musashi-Kosugi Hospital, 1-396, Kosugi-cho, Nakahara-ku, Kawasaki, Kanagawa, 211-8533, Japan. 5. 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.
Abstract
BACKGROUND: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). METHODS: 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. RESULTS: 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. CONCLUSIONS: Add-on TLV may increase both renal water and Na excretion in CHF patients with advanced CKD to a greater degree than increased FUR.
RCT Entities:
BACKGROUND: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). METHODS: 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. RESULTS: 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. CONCLUSIONS: Add-on TLV may increase both renal water and Na excretion in CHFpatients with advanced CKD to a greater degree than increased FUR.
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