Low-Dose Rapamycin ( Sirolimus) Effects in Autosomal Dominant Polycystic Kidney Disease: An Open-Label Randomized Controlled Pilot Study
Low-Dose Rapamycin ( Sirolimus) Effects in Autosomal Dominant Polycystic Kidney Disease: An Open-Label Randomized Controlled Pilot Study
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DOI：
10.2215/cjn.02650313
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发表时间：
2014-05-07
影响因子：
9.8
通讯作者：
Herts, Brian R.
中科院分区：
文献类型：
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作者：
Braun, William E.;Schold, Jesse D.;Herts, Brian R.
背景和目的关于雷帕霉素抑制剂治疗常染色体显性多囊肾病（ADPKD）的两项最大的哺乳动物靶点研究表明，在总肾容量（TKV）或eGFR的主要终点上没有明显的益处。本研究评估了两种水平的雷帕霉素对12个月i -125-碘甲酸酯GFR （iGFR）变化的影响，以iGFR为主要终点，TKV为次要终点。设计、环境、参与者和测量在一项为期12个月的开放标签试点研究中，30名ADPKD成年患者被随机分配到低剂量（LD）雷帕霉素（雷帕霉素通过血液水平，2-5 ng/ml） （LD组，n=10）、标准剂量（STD）雷帕霉素通过水平（bb0 5-8 ng/ml） （STD组，n=10）或标准治疗（SC组，n=10）。他们用iGFR和非对比计算机断层扫描进行评估。结果LD组12个月时iGFR变化显著增高（7.712.5 ml/min / 1.73 m）；n=9)比SC组（-11.2 +/- 9.1 ml/min / 1.73 m） (2)；n=9) (LD vs SC: P
Background and objectivesThe two largest studies of mammalian target of rapamycin inhibitor treatment of autosomal dominant polycystic kidney disease (ADPKD) demonstrated no clear benefit on the primary endpoint of total kidney volume (TKV) or on eGFR. The present study evaluated two levels of rapamycin on the 12-month change in I-125-iothalamate GFR (iGFR) as the primary endpoint and TKV secondarily.Design, setting, participants, & measurementsIn a 12-month open-label pilot study, 30 adult patients with ADPKD were randomly assigned to low-dose (LD) rapamycin (rapamycin trough blood level, 2-5 ng/ml) (LD group, n=10), standard-dose (STD) rapamycin trough level (>5-8 ng/ml) (STD group, n=10), or standard care (SC group, n=10). They were evaluated with iGFR and noncontrast computed tomography.ResultsChange in iGFR at 12 months was significantly higher in the LD group (7.712.5 ml/min per 1.73 m(2); n=9) than in the SC group (-11.2 +/- 9.1 ml/min per 1.73 m(2); n=9) (LD versus SC: P