KANSAS POLYCYSTIC KIDNEY IMAGING PROGRAM

大多数常染色体显性遗传性多囊肾病(ADPKD)和常染色体隐性遗传性多囊肾病(ARPKD)患者发展为终末期肾功能衰竭。初步研究表明，囊性肾脏的体积与其在GFR中反映的功能呈负相关。然而，目前还没有办法在病程早期确定患有PKD的人在正常预期寿命内是否注定会经历肾功能衰竭。为了达到RFA的目标，我们将开发一个PCC来评估以下具体目标：目的1.收集具有良好特征的PKD(ADPKD)的个体队列，他们有相对较高的进展到终末期肾脏疾病(ESRD)的风险。ADPKD受试者将从具有一个或多个进展危险因素的地区选择，包括：终末期肾病家族史、男性、多胎、高血压、蛋白尿和血尿。ARPKD受试者将主要从那些超过一岁而没有透析存活的人中挑选。目的：比较和评价MR、B超和CT快速采集的肾脏图像在PKD典型病例中的准确性和可重复性。这些研究将在囊性肾的体模模型中进行，以确定每种方法的最佳精密度和准确度，并在选定的肾囊性变从轻微到严重的患者中进行比较。然后，将按照下一个目标的概述，对PKD主题进行连续研究。目的3.评估PKD受试者肾脏形态计量学的序贯变化与进展性疾病的其他替代标记物的关系。受试者将以预定的时间间隔进行成像，以确定：a)总肾体积、总囊体积和总实质体积的变化率；b)“功能性”实质体积的变化率；c)单个囊体积的变化率；d)囊肿在肾内的分布与进展因素的关系；e)与肾脏增大和实质体积有关的疾病进展替代标记物的表达变化；以及f)囊肿生长与囊内液体积聚假说的关系。这些研究的成功完成将确定临床上可靠的方法，在肾小球滤过率发生可测量的变化和肾脏超微结构出现不可逆转的变化之前确定PKD的进展速度。

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.