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.
Keywords: CHF; CKD; Renal solute excretion; Renal water excretion; Vasopressin V2 receptor antagonist.