Abstract：
OBJECTIVE: Evidence on the long-term use of tolvaptan in autosomal dominant polycystic kidney disease (ADPKD) is limited. The aim was to evaluate the tolvaptan effectiveness and safety in real clinical setting.
METHODS: A single-center observational study (2016-2022) involving ADPKD patients treated with tolvaptan was conducted. Annual change in serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) before and after treatment initiation were evaluated. Change in total kidney volume (TKV), blood pressure (BP) and urinary albuminuria at 12, 24 and 36 months after initiation were also determined. Adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 were analyzed.
RESULTS: A total of 22 patients were included. No significant differences pre- vs post tolvaptan treatment in annual rate of change in eGFR (-3.52ml/min/1.73m2 [-4.98%] vs -3.98ml/min/1.73m2 [-8.48%], p=0.121) and sCr (+0.06mg/dL [4.22%] vs +0.15mg/dL [7.77%], p=0.429) were observed. Tolvaptan improved urinary osmolality at 12 (p=0.019) and 24 months (p=0.008), but not at 36 months (p=0.11). There were no changes in TKV, BP control and urinary albuminuria at 12, 24 or 36 months. A worse response was shown in patients with rapid kidney function decline (p=0.042). A 36.4% of the patients developed grade III/IV AEs. A 22.7% discontinued treatment due to unacceptable toxicity.
CONCLUSIONS: This study shows a modest benefit of tolvaptan in ADPKD patients, as well as safety concerns.
METHODS: A single-center observational study (2016-2022) involving ADPKD patients treated with tolvaptan was conducted. Annual change in serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) before and after treatment initiation were evaluated. Change in total kidney volume (TKV), blood pressure (BP) and urinary albuminuria at 12, 24 and 36 months after initiation were also determined. Adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 were analyzed.
RESULTS: A total of 22 patients were included. No significant differences pre- vs post tolvaptan treatment in annual rate of change in eGFR (-3.52ml/min/1.73m2 [-4.98%] vs -3.98ml/min/1.73m2 [-8.48%], p=0.121) and sCr (+0.06mg/dL [4.22%] vs +0.15mg/dL [7.77%], p=0.429) were observed. Tolvaptan improved urinary osmolality at 12 (p=0.019) and 24 months (p=0.008), but not at 36 months (p=0.11). There were no changes in TKV, BP control and urinary albuminuria at 12, 24 or 36 months. A worse response was shown in patients with rapid kidney function decline (p=0.042). A 36.4% of the patients developed grade III/IV AEs. A 22.7% discontinued treatment due to unacceptable toxicity.
CONCLUSIONS: This study shows a modest benefit of tolvaptan in ADPKD patients, as well as safety concerns.
摘要：
目的：长期使用托伐普坦治疗常染色体显性遗传性多囊肾病（ADPKD）的证据有限。目的是评估托伐普坦在实际临床环境中的有效性和安全性。
方法：进行了一项单中心观察性研究（2016-2022年），涉及使用托伐普坦治疗的ADPKD患者。评估治疗开始前后血清肌酐（sCr）和估计肾小球滤过率（eGFR）的年度变化。总肾脏体积（TKV）的变化，还测定了开始后12,24和36个月的血压（BP）和尿白蛋白。根据不良事件通用术语标准(CTCAE)v5.0分析不良事件(AE)。
结果：共纳入22例患者。托伐普坦治疗前后eGFR年变化率无显著差异(-3.52ml/min/1.73m2[-4.98%]vs-3.98ml/min/1.73m2[-8.48%],p=0.121)和sCr(+0.06mg/dL[4.22%]vs+0.15mg/dL[7.77%],观察到p=0.429）。托伐普坦在12个月（p=0.019）和24个月（p=0.008）时改善了尿渗透压，但不是在36个月（p=0.11）。TKV没有变化,12、24或36个月时血压控制和尿白蛋白。在肾功能快速下降的患者中显示出更差的反应（p=0.042）。36.4%的患者出现III/IV级AE。22.7%由于不可接受的毒性而停止治疗。
结论：本研究显示托伐普坦对ADPKD患者有适度的益处，以及安全问题。
方法：进行了一项单中心观察性研究（2016-2022年），涉及使用托伐普坦治疗的ADPKD患者。评估治疗开始前后血清肌酐（sCr）和估计肾小球滤过率（eGFR）的年度变化。总肾脏体积（TKV）的变化，还测定了开始后12,24和36个月的血压（BP）和尿白蛋白。根据不良事件通用术语标准(CTCAE)v5.0分析不良事件(AE)。
结果：共纳入22例患者。托伐普坦治疗前后eGFR年变化率无显著差异(-3.52ml/min/1.73m2[-4.98%]vs-3.98ml/min/1.73m2[-8.48%],p=0.121)和sCr(+0.06mg/dL[4.22%]vs+0.15mg/dL[7.77%],观察到p=0.429）。托伐普坦在12个月（p=0.019）和24个月（p=0.008）时改善了尿渗透压，但不是在36个月（p=0.11）。TKV没有变化,12、24或36个月时血压控制和尿白蛋白。在肾功能快速下降的患者中显示出更差的反应（p=0.042）。36.4%的患者出现III/IV级AE。22.7%由于不可接受的毒性而停止治疗。
结论：本研究显示托伐普坦对ADPKD患者有适度的益处，以及安全问题。
