PKD, INNOVATIVE IMAGING TO ASSESS PROGRESSION (PCC)

本应用程序的总体目标是在肾功能不全发展之前建立囊肿进展的自然史，并确定可作为多囊肾病疾病活动和进展的替代标记物的影像学和生化参数。具体目的包括：1)确定肾囊肿、实质体积和肾血流的变动率，它们对年龄、性别、种族背景和PKD基因型的依赖性，以及它们与本研究诊断为ADPKD的青春期前、青春期和年轻成人患者（7-20岁）和未患病兄弟姐妹中疾病活动或进展的其他可能的生化标志物的相关性。2)确定绝对和相对肾囊肿和实质体积、肾血流量及其随时间变化的预测价值，以及疾病活动性生化标志物对研究开始时ADPKD患者血清囊肿胱抑素C水平和非放射性标记碘酸盐清除率测定的肾功能下降率的预测价值，血清肌酐正常。3)测定ADPKD患者肾囊肿及实质体积变化率、肾血流量、与妊娠相关的疾病活动性生化指标。4)研究ADPKD患者肾囊肿及实质体积、肾血流量、与妊娠相关的疾病活动性生化指标。4)研究有症状的早发性ADPKD或ARPKD及不同程度肾功能不全患儿肾囊肿及实质体积、肾血流量、肝脏影像学参数及疾病活动性或进展的生化指标。5)应用磁共振弹性成像技术研究ADPKD和ARPKD肾和肝实质的力学特性。我们建议使用基于最先进的磁共振技术和3d超声的创新成像研究。我们期望本研究的结果将进一步深入了解多囊肾病的发病机制，并有助于设计未来的干预试验，缩短确定疗效所需的观察期。

The overall goals of this application are to establish the natural history of cyst progression prior to the development of renal insufficiency and to identify imaging and biochemical parameters which can be used as surrogate markers of disease activity of progression in polycystic kidney disease. Specific aims include: 1) Determine the rate of change of renal cysts and parenchyma volumes and of renal blood flow, their dependency on age, gender, ethnic background, and PKD genotype, and their correlation with other possible biochemical markers of disease activity or progression in prepubertal, pubertal and young adult patients with ADPKD (7-20 years) diagnosed for the purpose of the study and in non- affected sibling. 2) Determine the predictive value of absolute and relative renal cyst and parenchyma volumes, of renal blood flow, and of their changes over time, and of biochemical markers of disease activity for the rate of decline of renal function measured by serum cyst cystatin C levels and non-radiolabeled iothalamate clearance in patients with ADPKD and normal serum creatinine at the onset of the study. 3) Determine the rate of change of renal cyst and parenchyma volumes, renal blood flow, and biochemical markers of disease activity associated with pregnancy in ADPKD. 4) Study the renal cyst and parenchyma volumes, renal blood flow, and biochemical markers of disease activity associated with pregnancy in ADPKD. 4) Study the renal cyst and parenchyma v and parenchyma volumes, renal blood flow, liver imaging parameters, and biochemical markers of disease activity or progression in children with symptomatic early onset ADPKD or ARPKD and variable degrees of renal dysfunction. 5) Study the mechanical properties of the renal and hepatic parenchyma in ADPKD and ARPKD, using MR elastography. We propose to use innovative imaging studies based on state-of-the-art MR technology and 3d ultrasound. We anticipate that the results of this study will provide further insight into the pathogenesis of polycystic kidney disease and will facilitate the design of future intervention trials, shortening the observation period necessary to determine efficacy.