Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Department of Nephrology and Hypertension, Yokohama City University Medical Center, 45-7, Urafune-cho, Minami-ku, Yokohama, 232-0024, Japan.
Clin Exp Nephrol. 2022 Sep;26(9):851-858. doi: 10.1007/s10157-022-02224-x. Epub 2022 Apr 26.
Tolvaptan (TLV) is reported to improve diuretic effects in patients with chronic kidney disease (CKD) when furosemide (FUR) is not sufficiently effective. However, it is not clear whether TLV addition is effective for advanced CKD patients with heart failure.
An open-label, parallel-group randomized trial was performed. The subjects were 33 patients with CKD stage G3-G5 who had fluid overload despite taking 20-100 mg/day FUR. They were divided into two groups: a group administered 15 mg/day TLV plus their original FUR dose for 7 days (TLV group), and a group administered 120-200 mg/day FUR (i.e., 100 mg/day over their previous dose) for 7 days (FUR group).
The mean change in urine volume was significantly higher in the TLV group compared to the FUR group (637 ml vs 119 ml; p < 0.05). The difference was greater when the urine osmolality before treatment was high. Serum creatinine was increased only in the FUR group. The incidence of worsening renal function (WRF) was significantly lower in the TLV group (18.8% vs 58.8%; p < 0.05). Serum sodium decreased significantly in the FUR group, but did not change in the TLV group.
In patients with advanced CKD with fluid overload, the addition of TLV achieved a significantly higher urine volume with less adverse effects on renal function compared with increasing the dose of FUR. The efficacy and safety of TLV were higher in patients who had higher urine osmolality and lower serum sodium before treatment.
UMIN000014763.
托伐普坦（TLV）据报道可增强呋塞米（FUR）对慢性肾脏病（CKD）患者的利尿作用，但对于心力衰竭的晚期 CKD 患者，TLV 加用是否有效尚不清楚。
进行了一项开放标签、平行组随机试验。受试者为 33 例 CKD G3-G5 期患者，尽管服用 20-100mg/d FUR 仍存在液体超负荷。将他们分为两组：TLV 组加用 15mg/d TLV 联合原 FUR 剂量，共 7 天；FUR 组加用 120-200mg/d FUR（即较前剂量增加 100mg/d），共 7 天。
与 FUR 组相比，TLV 组的尿量平均变化显著更高（637ml 比 119ml；p<0.05）。治疗前尿渗透压高时差异更大。仅 FUR 组的血清肌酐增加。TLV 组肾功能恶化（WRF）的发生率显著更低（18.8%比 58.8%；p<0.05）。FUR 组血清钠显著降低，但 TLV 组无变化。
在晚期 CKD 合并液体超负荷的患者中，与增加 FUR 剂量相比，加用 TLV 可显著增加尿量，对肾功能的不良影响更小。治疗前尿渗透压较高和血清钠较低的患者，TLV 的疗效和安全性更高。
UMIN000014763。
