Effect of Statin Therapy on Disease Progression in Children with ADPKD

他汀类药物治疗对 ADPKD 儿童疾病进展的影响

• 批准号: 8144692
• 负责人: ROBERT W SCHRIER
• 金额: $ 76.5万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-20 至 2012-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8144692
• 关键词: Accounting; Adult; Affect; Albumins; Angiotensin-Converting Enzyme Inhibitors; Autosomal Dominant Polycystic Kidney; Cardiovascular Diseases; Child; Childhood; Coenzyme A; Cystic kidney; Development; Disease; Disease Progression; Early treatment; End stage renal failure; Endothelium; Enzyme Inhibition; Europe; Excretory function; Fetus; Goals; Heart Diseases; Hypertension; Individual; Inherited; Kidney; Kidney Diseases; Left Ventricular Mass; Life; Lisinopril; Magnetic Resonance Imaging; Measures; Medicine; Microalbuminuria; Morbidity - disease rate; Patients; Peptidyl-Dipeptidase A; Placebos; Pravastatin; Randomized; Renal function; Ultrasonography; United States; Vasodilation; design; double-blind placebo controlled trial; indexing; inhibitor/antagonist; mortality; urinary; young adult

DESCRIPTION (provided by applicant): ADPKD is the most common hereditary kidney disease, affecting 1 in 400 to 1000 individuals and accounting for 4% of end-stage renal disease in the United States and 8-10% in Europe. The condition is characterized by progressive development of kidney cysts with kidney enlargement and associated loss of kidney function. High blood pressure and cardiovascular disease are common in patients with ADPKD. Although the condition is often thought to affect primarily adults, it is clear that the disease can be present in the fetus and young children. This study is designed to determine if treatment with the medicines, pravastatin and lisinopril, can slow the progression of kidney and heart disease when initiated early in life in patients with ADPKD. The goal of this randomized double-blind placebo-controlled trial is to determine whether treatment with the 3-hydroxy-3- methylglutaryl coenzyme A (HMG coA) inhibitor pravastatin will delay the progression of renal and cardiovascular disease over a three-year period in children and young adults with autosomal dominant polycystic kidney disease (ADPKD) who are receiving angiotensin converting enzyme inhibitors. The primary endpoint of the study will be achieved in subjects with 20% or greater change over the three-year interval in any or all of the following four endpoints: 1) total renal volume as assessed by MRI; 2) left ventricular mass index as assessed by MRI; 3) urinary albumin excretion; and 4) endothelial-dependent vasodilation as assessed by brachial ultrasonography. This study will involve pediatric subjects because we believe that early intervention is critical if we are to ameliorate the morbidity and mortality associated with this condition. If pravastatin is shown to be effective in ameliorating progression of renal and cardiovascular disease in this study, routine management of affected patients will be drastically altered.

描述（由申请人提供）：ADPKD是最常见的遗传性肾脏疾病，影响了400至1000个人中的1个，占美国终末期肾脏疾病的4％，欧洲占8-10％。该病情的特征是肾脏囊肿逐渐发展，并具有肾脏肿大以及肾功能的相关损失。高血压和心血管疾病在ADPKD患者中很常见。尽管这种病通常被认为主要影响成年人，但很明显，该疾病可以存在于胎儿和幼儿中。这项研究旨在确定药物治疗Pravastatin和Lisinopril是否会在ADPKD患者生命的早期开始时降低肾脏和心脏病的进展。这项随机双盲安慰剂对照试验的目的是确定用3-羟基-3-甲基戊二酰辅酶A（HMG COA）抑制剂pravastatin治疗是否会延迟肾脏和心血管疾病的进展，在三年的周期内延迟患有常染色体显性多囊性肾脏疾病（ADPKD）的儿童和年轻人正在接受血管紧张素转化酶抑制剂。该研究的主要终点将在以下四个终点中的三年间隔内的20％或更高时间的受试者中实现：1）MRI评估的总肾脏量； 2）MRI评估的左心室质量指数； 3）尿白蛋白排泄； 4）通过臂超声检查评估的内皮依赖性血管舒张。这项研究将涉及儿科受试者，因为我们认为，如果我们要改善与这种情况相关的发病率和死亡率，早期干预至关重要。如果在这项研究中证明普伐他汀在改善肾脏和心血管疾病的进展方面有效，那么受影响患者的常规管理将发生巨大改变。