ANTIHYPERTENSIVE THERAPY IN CHILDREN WITH ADPKD

ADPKD 儿童的抗高血压治疗

• 批准号: 7605052
• 负责人: MELISSA A CADNAPAPHORNCHAI
• 金额: $ 7.38万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605052
• 关键词: Age; Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Autosomal Dominant Polycystic Kidney; Blood Pressure; Child; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Cystic kidney; Enalapril; End stage renal failure; Family; Funding; Gender; Grant; Growth; Height; Hydrochlorothiazide; Hypotension; Inflammatory; Institution; Kidney; Left Ventricular Mass; Magnetic Resonance Imaging; Measurement; Measures; Metoprolol; Microalbuminuria; Morbidity - disease rate; Numbers; Outcome; Pharmaceutical Preparations; Randomized; Recommendation; Research; Research Personnel; Resources; Screening procedure; Source; Standards of Weights and Measures; Testing; Ultrasonography; United States National Institutes of Health; blood pressure regulation; cytokine; indexing; mortality; normotensive; size; young adult

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term objective of this research is to reduce the morbidity and mortality of autosomal dominant polycystic kidney disease (ADPKD). This study is a 5-year clinical trial to test the hypothesis that intensive blood pressure control with angiotensin converting enzyme inhibitors (ACEI) as first-line drugs will slow the progression of ADPKD in children. Progression in children will be measured by increase in renal volume, which reflects an increased number and size of renal cysts, as determined by ultrasonography. Secondary aims are: 1) to evaluate the effect of intensive blood pressure control on left ventricular mass index, on microalbuminuria, and on the activation level of several growth-related and inflammatory cytokines; and 2) to compare measurement of renal volume by ultrasonography and magnetic resonance imaging (MRI). Three groups of children and young adults, age 4 to 21 years, will be randomized to different treatments: 1. Hypertensive subjects with blood pressures above the 95th percentile for age-, gender- and height-matched children will be randomized to intensive or standard blood pressure control, with intensive control defined as lowering blood pressure to below 50th percentile and standard control as lowering blood pressure to 90th percentile. 2. Borderline hypertensive subjects with blood pressures between the 75th and 95th percentile will be randomized to treatment to lower the blood pressure to below 50th percentile or to no treatment. 3. Normotensive subjects (blood pressure between the 25th and 75th percentile) with severe ADPKD (SADPKD, defined as > 10 renal cysts) will be randomized to treatment with ACEI or to no treatment. The first-line drug for all groups is enalapril. Second-line drugs for groups 1 and 2 are amlodipine, metoprolol, and hydrochlorothiazide. The primary outcome variable is the increase in renal volume per year, compared between the different blood pressure levels or between ACEI treatment and no treatment. If intensive blood pressure control or treatment with ACEI can be shown to reduce progressive renal enlargement, it would change screening and treatment recommendations for children from ADPKD families and would have a major impact on the morbidity associated with enlarged kidneys and with end-stage renal disease in ADPKD.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 这项研究的长期目标是降低常染色体显性多囊肾病（ADPKD）的发病率和死亡率。这项研究是一项为期 5 年的临床试验，旨在检验以下假设：使用血管紧张素转换酶抑制剂 (ACEI) 作为一线药物强化血压控制将减缓儿童 ADPKD 的进展。儿童的进展将通过肾脏体积的增加来衡量，这反映了超声检查确定的肾囊肿数量和大小的增加。 次要目标是：1）评估强化血压控制对左心室质量指数、微量白蛋白尿以及几种生长相关细胞因子和炎症细胞因子激活水平的影响； 2) 比较超声检查和磁共振成像 (MRI) 对肾脏体积的测量结果。三组 4 至 21 岁的儿童和年轻人将被随机分配接受不同的治疗： 1. 年龄、性别和身高匹配的儿童血压高于 95% 的高血压受试者将被随机分配至强化治疗或标准治疗血压控制，强化控制定义为将血压降低到第 50 个百分位以下，标准控制定义为将血压降低到第 90 个百分位。 2. 血压在 75% 和 95% 之间的临界高血压受试者将被随机接受将血压降至 50% 以下的治疗或不接受治疗。 3.患有严重ADPKD（SADPKD，定义为> 10个肾囊肿）的血压正常受试者（血压在25%和75%之间）将被随机分配接受ACEI治疗或不接受治疗。所有人群的一线药物是依那普利。第 1 组和第 2 组的二线药物是氨氯地平、美托洛尔和氢氯噻嗪。主要结果变量是不同血压水平之间或 ACEI 治疗与不治疗之间每年肾体积的增加。如果强化血压控制或 ACEI 治疗可以减少进行性肾肿大，这将改变对 ADPKD 家族儿童的筛查和治疗建议，并对肾脏肿大和终末期肾病相关的发病率产生重大影响在 ADPKD 中。