KANSAS POLYCYSTIC KIDNEY IMAGING PROGRAM

堪萨斯州多囊肾成像计划

• 批准号: 6624906
• 负责人: JARED JAMES GRANTHAM
• 金额: $ 48.43万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6624906
• 关键词: autosomal dominant trait; autosomal recessive trait; bioimaging /biomedical imaging; chronic renal failure; clinical research; computed axial tomography; cooperative study; disease /disorder proneness /risk; human subject; kidney function; pathologic process; polycystic kidney; ultrasound

The majority of patients with autosomal dominant polycystic kidney disease (ADPKD types 1 and 2) and autosomal recessive polycystic kidney disease (ARPKD) develop end-stage renal failure. Preliminary studies indicate an inverse correlation between the volume of cystic kidneys and their function reflected in the GFR. However, there is presently no way to determine early in the course if an individual with PKD is destined to experience renal failure in a normal life expectancy. To meet the objectives of the RFA we will develop a PCC to evaluate the following specific aims: Aim 1. Assemble a cohort of individuals with well-characterized PKD (ADPKD) who are at relatively high risk to experience progression to end-stage-renal disease (ESRD). ADPKD subjects will be selected from the region who have one or more risk factors for progression, including: family history of ESRD, male gender, multiple pregnancies, hypertension, proteinuria and hematuria. ARPKD subjects will be selected primarily from those who have survived without dialysis beyond the first year of life. Aim 2. Compare and evaluate the accuracy and reproducibility of renal images obtained by rapid acquisition MR, ultrasound and CT in representative examples of PKD. These studies will be done in phantom models of cystic kidney in order to determine optimum precision and accuracy of each method in comparison to the other, and in selected patients with renal cystic changes ranging from mild to severe. PKD subjects will then be studied serially as outlined in the next aim. Aim 3. Evaluate sequential changes in renal morphometrics in subjects with PKD in relation to other surrogate markers for progressive disease. Subjects will be imaged at predefined intervals in order to determine: a) The rate of change in total kidney volume, total cyst volume and total parenchymal volume; b) The rate of change of "functional" parenchymal volume; c) The rate of change of individual cyst volume; d) The intra- renal distribution of cysts in relation to progression factors; e) Changes in the expression of surrogate markers of disease progression in relation to renal enlargement and parenchyma volume, and ; f) the relation of cyst growth to hypotheses of intra-cyst fluid accumulation. Successful completion of these studies will identify clinically reliable methods for determining the rate of progression of PKD before there are measurable changes in GFR and irreversible changes in renal ultra- structure.

大多数常染色体显性多囊肾病（ADPKD 1 型和 2 型）和常染色体隐性多囊肾病 (ARPKD) 患者会出现终末期肾功能衰竭。初步研究表明囊性肾的体积与其 GFR 中反映的功能之间存在负相关。然而，目前还没有办法在病程早期确定多囊肾患者在正常预期寿命内是否注定会出现肾衰竭。为了实现 RFA 的目标，我们将开发 PCC 来评估以下具体目标： 目标 1. 聚集一组具有明确特征的 PKD (ADPKD) 的个体，这些个体处于进展为终末期肾病的风险相对较高疾病（终末期肾病）。 ADPKD受试者将从具有一种或多种进展危险因素的地区选择，包括：ESRD家族史、男性、多胎妊娠、高血压、蛋白尿和血尿。 ARPKD 受试者将主要选自那些在生命第一年之后未进行透析而存活的受试者。目标 2. 比较和评估 PKD 代表性病例中通过快速采集 MR、超声和 CT 获得的肾脏图像的准确性和再现性。这些研究将在囊性肾的体模模型中进行，以确定每种方法与其他方法相比的最佳精度和准确度，并在选定的肾囊性变化从轻度到重度的患者中进行。然后，PKD 受试者将按照下一个目标中的概述进行连续研究。目标 3. 评估 PKD 受试者肾脏形态测量的连续变化与进展性疾病的其他替代标志物的关系。将按照预定的时间间隔对受试者进行成像，以确定： a) 肾脏总体积、囊肿总体积和实质总体积的变化率； b)“功能性”实质体积的变化率； c) 单个囊肿体积的变化率； d) 囊肿的肾内分布与进展因素的关系； e) 与肾脏增大和实质体积相关的疾病进展替代标志物的表达变化； f) 囊肿生长与囊肿内积液假设的关系。这些研究的成功完成将确定临床上可靠的方法，用于在 GFR 发生可测量的变化和肾脏超微结构发生不可逆转的变化之前确定 PKD 的进展速度。