Kansas Polycystic Kidney Imaging Program (CRISPII)

描述（由申请人提供）：常染色体显性遗传性多囊肾病（ADPKD）是致残性发病的主要原因，也是世界上第四大终末期肾衰竭原因，影响超过50万美国公民和全球数百万人。2000年，亚拉巴马大学、埃默里大学、堪萨斯大学、马约诊所和华盛顿大学圣路易斯分校的研究人员联合起来创建了多囊肾病放射学研究联盟（CRISP-I）。本研究的主要目的是：（1）开发和测试成像技术的准确性和可重复性，以监测肾囊肿大小和实质的变化！参与。(2)建立和维护统一、准确收集的信息数据库。(3)维护和提供这些数据，以促进在不久的将来规划和实施临床上适当的干预措施。CRISP-II的目标是扩展CRISPI的观察结果，以便：1）在肾脏/囊肿增大的速率与定性和定量终点之间建立明确的联系。2)提供足够灵敏和准确的疾病进展标志物（肾脏体积），用作旨在预防疾病进展的临床试验的主要结局标志物。3)开发和测试疾病进展的其他生物标志物。具体目标是：目标1：扩展CRISP-I的初步观察结果，以确定定量（肾脏体积和肝脏和肾脏囊肿体积）或定性（囊肿分布和特征）结构参数预测肾功能不全的程度。目标二：扩展CRISP-I的初步观察结果，以确定通过MR技术进行的年龄和性别调整的肾血流量测量在多大程度上预测肾脏生长速率;以及，肾血流量和肾脏体积预测ADPKD的肾功能下降速率。目标3：彻底分析来自CRISP-I和CRISP-II扩展的活体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，并收集已知患有ADPKD的CRISP家族成员的DMA样本和临床信息，用于未来的研究，以检查基因型-表型相关性并识别遗传修饰因子。

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 parenchyma! 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.