Data Coordinating and Image Analysis for CRISP-II

描述(申请人提供)：常染色体显性遗传性多囊肾病(ADPKD)是致残性疾病的主要原因，也是世界上导致终末期肾功能衰竭的第四大原因，影响着50多万美国公民和全球数百万人。阿拉巴马大学、埃默里大学、堪萨斯大学、梅奥诊所和华盛顿大学圣路易斯分校的研究人员于2000年联合成立了多囊肾病放射研究联盟(CRISP-I)。这项研究的主要目的是：(1)开发和测试监测肾囊肿大小和实质受累的影像技术的准确性和重复性。(2)建立和维护统一准确收集信息的数据库。(3)维护和提供这些数据，以便在不久的将来规划和实施临床上适当的干预措施。CRISP-I的目标是扩大CRISPI的观察范围，以便：1)明确地指出肾脏/囊肿率与定性和定量终点之间的联系。2)提供足够灵敏和准确的疾病进展标志(肾脏体积)，以在旨在预防疾病进展的临床试验中用作主要结果标志。3)开发和测试其他疾病进展的生物标志物。其具体目的是：目的1：扩展CRISP-I的初步观察，以确定定量(肾体积和肝肾囊肿体积)或定性(囊性分布和性质)结构参数预测肾功能不全的程度。目的：扩展CRISP-I的初步观察，以确定在多大程度上，年龄和性别调整的MR技术测量的肾血流可以预测肾脏的生长速度；肾血流和肾体积可以预测ADPKD患者的肾功能减退的速度。目的3：详尽分析CRISP-I和CRISP-II扩展的活数据库和存储的生物样本，以开发和测试新的指标来量化和监测疾病进展，并从已知患有ADPKD的CRISP家族成员收集DMA样本和临床信息，以用于未来的研究，以检查基因-表型相关性和确定遗传修饰因素。

DESCRIPTION (provided by applicant): Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of disabling morbidity and is the fourth leading cause of end-stage renal failure in the world, affecting more than 500,000 U.S. citizens and millions more worldwide. Researchers at the University of Alabama, Emory University, University of Kansas, Mayo Clinic and Washington University St. Louis joined together in 2000 to create the Consortium for Radiologic Studies of Polycystic Kidney Disease (CRISP-I). The primary objectives of this investigation were to: (1) Develop and test the accuracy and reproducibility of imaging techniques to monitor changes in renal cyst size and parenchymal involvement. (2) Establish and maintain a database of uniformly and accurately collected information. (3) Maintain and make available such data to facilitate the planning and implementation of clinically appropriate interventions in the near future. The goals of CRISP-I I are to extend the observations of CRISPI in order to: 1) Draw unequivocal linkage between the rate of kidney/cyst enlargement and qualitative and quantitative end-points. 2) Provide a marker of disease progression (kidney volume) sensitive and accurate enough to be used as a primary outcome marker in clinical trials aiming to forestall disease progression. 3) Develop and test other bio-markers of disease progression. The specific aims are: Aim 1: Extend the preliminary observations of CRISP-I to ascertain the extent to which quantitative (kidney volume and hepatic and kidney cyst volume) or qualitative (cyst distribution and character) structural parameters predict renal insufficiency. Aim 2: Extend the preliminary observations of CRISP-I to ascertain the extent to which age and sex-adjusted measurements of renal blood flow by MR technology predict the rate of renal growth; and, renal blood flow and kidney volume predict the rate of renal function decline in ADPKD. Aim 3: Exhaustively analyze the living database and stored biologic samples derived from CRISP-I and the CRISP-II extension to develop and test new metrics to quantify and monitor disease progression, and collect DMA samples and clinical information from CRISP family members known to have ADPKD for use in future studies to examine genotype-phenotype correlations and to identify genetic modifiers.