Roca Oporto F J, Andrades Gómez C, Montilla Cosano G, Aguilera A Luna, Rocha José L
Unidad de Gestión Clínica Nefrología, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
Nefrología, Departamento Medicina, Universidad de Sevilla, Sevilla, Spain.
Kidney Int Rep. 2024 Jan 12;9(4):1031-1039. doi: 10.1016/j.ekir.2024.01.020. eCollection 2024 Apr.
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).
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.
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 m 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).
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.
托伐普坦已被证明可减少常染色体显性遗传性多囊肾病（ADPKD）患者的肾脏体积并延缓疾病进展。然而，目前尚无生物标志物可用于指导剂量调整。我们旨在探讨基于尿渗透压（OsmU）临界值进行托伐普坦个体化剂量调整的可能性。
这项前瞻性队列研究纳入了疾病进展迅速的ADPKD患者。托伐普坦治疗起始剂量为45/15mg，并根据OsmU进行增加，上限设定为200mOsm/kg。在3年随访期间监测主要肾脏事件（治疗期间估计肾小球滤过率[eGFR]下降25%）、患者内eGFR斜率和副作用。
40名患者参与了该研究。在整个研究期间，OsmU均低于200mOsm/kg，大多数患者需要最低托伐普坦剂量（平均剂量，64[±10]mg），停药率较低（5%）。与治疗前相比，托伐普坦治疗期间eGFR的平均年下降率为每1.73m²-3.05（±2.41）ml/min，eGFR下降减少超过50%。20%的患者发生了主要肾脏事件（平均发病时间，31个月；95%置信区间[CI]=28-34）。
对于疾病进展迅速的ADPKD患者，基于OsmU进行托伐普坦个体化剂量调整，与参考研究相比，在降低eGFR下降方面具有益处，且停药率较低，副作用较少。需要进一步研究以确认在ADPKD患者中使用OsmU进行托伐普坦剂量调整的最佳策略。
