PDF(Pubmed)
Abstract：
UNASSIGNED: Tolvaptan has been shown to reduce renal volume and delay disease progression in autosomal-dominant polycystic kidney disease (ADPKD). However, no biomarkers are currently available to guide dose adjustment. We aimed to explore the possibility of individualized tolvaptan dose adjustments based on cut-off values for urinary osmolality (OsmU).
UNASSIGNED: This prospective cohort study included patients with ADPKD, with rapid disease progression. Tolvaptan treatment was initiated at a dose of 45/15 mg and increased based on OsmU, with a limit set at 200 mOsm/kg. Primary renal events (25% decrease in estimated glomerular filtration rate [eGFR] during treatment), within-patient eGFR slope, and side effects were monitored during the 3-year follow-up.
UNASSIGNED: Forty patients participated in the study. OsmU remained below 200 mOsm/kg throughout the study period, and most patients required the minimum tolvaptan dose (mean dose, 64 [±10] mg), with a low discontinuation rate (5%). The mean annual decline in eGFR was -3.05 (±2.41) ml/min per 1.73 m2 during tolvaptan treatment, compared to the period preceding treatment, corresponding to a reduction in eGFR decline of more than 50%. Primary renal events occurred in 20% of patients (mean time to onset, 31 months; 95% confidence interval [CI] = 28-34).
UNASSIGNED: Individualized tolvaptan dose adjustment based on OsmU in patients with ADPKD and rapid disease progression provided benefits in terms of reducing eGFR decline, compared with reference studies, and displayed lower dropout rates and fewer side effects. Further studies are required to confirm optimal strategies for the use of OsmU for tolvaptan dose adjustment in patients with ADPKD.
UNASSIGNED: This prospective cohort study included patients with ADPKD, with rapid disease progression. Tolvaptan treatment was initiated at a dose of 45/15 mg and increased based on OsmU, with a limit set at 200 mOsm/kg. Primary renal events (25% decrease in estimated glomerular filtration rate [eGFR] during treatment), within-patient eGFR slope, and side effects were monitored during the 3-year follow-up.
UNASSIGNED: Forty patients participated in the study. OsmU remained below 200 mOsm/kg throughout the study period, and most patients required the minimum tolvaptan dose (mean dose, 64 [±10] mg), with a low discontinuation rate (5%). The mean annual decline in eGFR was -3.05 (±2.41) ml/min per 1.73 m2 during tolvaptan treatment, compared to the period preceding treatment, corresponding to a reduction in eGFR decline of more than 50%. Primary renal events occurred in 20% of patients (mean time to onset, 31 months; 95% confidence interval [CI] = 28-34).
UNASSIGNED: Individualized tolvaptan dose adjustment based on OsmU in patients with ADPKD and rapid disease progression provided benefits in terms of reducing eGFR decline, compared with reference studies, and displayed lower dropout rates and fewer side effects. Further studies are required to confirm optimal strategies for the use of OsmU for tolvaptan dose adjustment in patients with ADPKD.
摘要：
■托伐普坦已被证明可以减少常染色体显性多囊肾病（ADPKD）的肾脏体积并延迟疾病进展。然而,目前尚无生物标志物可用于指导剂量调整.我们旨在探索基于尿渗透压（OsmU）的截止值对托伐普坦剂量进行个性化调整的可能性。
■这项前瞻性队列研究包括ADPKD患者，疾病进展迅速。托伐普坦治疗以45/15mg的剂量开始，并基于OsmU增加，限值设定为200mOsm/kg。原发性肾脏事件（治疗期间估计肾小球滤过率[eGFR]下降25%），患者内部eGFR斜率，并在3年随访期间监测副作用.
■40名患者参与了这项研究。OsmU在整个研究期间保持在200mOsm/kg以下，大多数患者需要托伐普坦的最小剂量(平均剂量，64[±10]mg)，低停药率（5%）。托伐普坦治疗期间，eGFR的年平均下降为每1.73m2-3.05（±2.41）ml/min，与治疗前相比，对应于eGFR下降50%以上。20%的患者发生原发性肾脏事件(平均发病时间，31个月；95%置信区间[CI]=28-34)。
■在ADPKD和快速疾病进展患者中基于OsmU的个体化托伐普坦剂量调整在减少eGFR下降方面提供了益处，与参考研究相比，并显示出较低的辍学率和较少的副作用。需要进一步的研究来确认OsmU用于ADPKD患者托伐普坦剂量调整的最佳策略。
■这项前瞻性队列研究包括ADPKD患者，疾病进展迅速。托伐普坦治疗以45/15mg的剂量开始，并基于OsmU增加，限值设定为200mOsm/kg。原发性肾脏事件（治疗期间估计肾小球滤过率[eGFR]下降25%），患者内部eGFR斜率，并在3年随访期间监测副作用.
■40名患者参与了这项研究。OsmU在整个研究期间保持在200mOsm/kg以下，大多数患者需要托伐普坦的最小剂量(平均剂量，64[±10]mg)，低停药率（5%）。托伐普坦治疗期间，eGFR的年平均下降为每1.73m2-3.05（±2.41）ml/min，与治疗前相比，对应于eGFR下降50%以上。20%的患者发生原发性肾脏事件(平均发病时间，31个月；95%置信区间[CI]=28-34)。
■在ADPKD和快速疾病进展患者中基于OsmU的个体化托伐普坦剂量调整在减少eGFR下降方面提供了益处，与参考研究相比，并显示出较低的辍学率和较少的副作用。需要进一步的研究来确认OsmU用于ADPKD患者托伐普坦剂量调整的最佳策略。
