Consortium for Radiologic Imaging Studies in Polycystic Kidney Disease (CRISP)

描述（由申请人提供）：常染色体显性遗传性多囊肾病（ADPKD）是发病的主要原因，是世界上ESRD的第四大原因，影响超过50万美国公民。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的研究人员于2000年联合起来创建了多囊肾病放射学研究联盟（CRISP I），并于2006年将匹兹堡大学纳入CRISP II。CRISP I和II的主要目的是：建立准确、可靠和可重现的基于磁共振的肾脏总体积（TKV）、肝囊肿体积（LCV）、肾血流量（RBF）以及囊肿生长和扩张模式的测量值。基于对200名CRISP I/II参与者进行的7.3年纵向随访，我们现在可以1）确定TKV与定性（患者报告的结局）和定量（肾功能不全）终点之间的明确关系;以及2）确定与TKV和LCV相关的潜在可改变风险因素进行干预。TKV最终可用作临床试验中疾病进展的替代标志物。CRISP III的目标扩展了CRISP I/II的意见。CRISP III的总体目标是开发和增强最能预测ADPKD肾功能不全的预测模型。具体而言，目标1;扩展TKV和LCV的系列定量，以开发和测试预测肾功能不全风险的新模型。目标二：确定年龄和性别校正的RBF测量值预测TKV变化率的程度，并确定RBF和TKV是否独立预测发生肾功能不全的风险。目标3：制定方法，量化基线时肾囊肿数量、体积和地形对TKV和GFR后续病程以及肾功能不全风险的影响。目的4：扩大和分析CRISP生物样本，以改善基因型/表型和生物标志物研究。目标5。确定一小群CRISP参与者的强化饮食咨询和干预是否成功地改变了CRISP I中观察到的相对固定的钠摄入模式，并降低了多囊肾的生长速度。 公共卫生相关性：这些研究的结果将影响ADPKD患者的生活。在肾功能不全消失之前，早期开发疾病严重程度的预测标志物将导致治疗/药物开发效率提高，并导致ADPKD患者预期寿命延长和生活质量改善。

DESCRIPTION (provided by applicant): Autosomal dominant polycystic kidney disease (ADPKD) is a major cause of morbidity and is the fourth leading cause of ESRD In the world, affecting more than 500,000 U.S. citizens. Researchers at the University of Alabama, Emory University, University of Kansas, Mayo Clinic and Washington University joined together in 2000 to create the Consortium for Radiologic Studies of Polycystic Kidney Disease (CRISP I) and In 2006 included the University of Pittsburgh in place of Washington University for CRISP II. The primary objectives of CRISP I and II were to: establish accurate, reliable and reproducible magnetic resonance based measurements of total kidney volume (TKV), liver cyst volume (LCV), renal blood flow (RBF), and patterns of cyst growth and expansion. Based on 7.3 years of longitudinal follow-up in 200 CRISP I/I I participants, we can now 1) establish an unequivocal relationship between TKV and qualitative (patient reported outcomes) and quantitative (renal insufficiency) end-points; as well as 2) identify potential modifiable risk factors associating with TKV and LCV to intervene upon. TKV ultimately may be used as a surrogate marker of disease progression in clinical trials. The goals of CRISP III extend the observations of CRISP l/ll. The overarching Aim for CRISP III is to develop and enhance prediction models that best predict renal insufficiency in ADPKD. Specifically, Aim 1; Extend the serial quantification of TKV and LCV to develop and test new models for predicting the risk of developing renal insufficiency. Aim 2: Determine the extent to which age and sex-adjusted measurements of RBF predict the rate of change in TKV and determine if RBF and TKV independently predict the risk of developing renal insufficiency. Aim 3: Develop methods to quantify the influence of renal cyst number, volume, and topography at baseline on the subsequent course of TKV and GFR and the risk of developing renal insufficiency. Aim 4: Expand and analyze CRISP biological samples to improve genotype/phenotype and biomarker studies. Aim 5. Determine whether intensive dietary counseling and intervention in a small group of CRISP participants is successful in modifying the relatively fixed pattern of sodium intake observed in CRISP I and reducing the rate of growth of the polycystic kidneys. PUBLIC HEALTH RELEVANCE: The results of these studies will impact the lives of patients with ADPKD. Developing predictive markers of disease severity early, prior to loss of renal insufficiency will result in increased efficiency of theray/drug development and result in increased life expectancy and improved quality of life in patients with ADPKD.