Research Project Core 2

项目2摘要 《慢性肾脏病进展的影像生物标记物的推导和验证》 需要生物标记物来识别患有先天性肾脏和尿路异常的儿童 生命早期的慢性肾脏病(CAKUT)是未来CKD进展的高风险因素。早期识别儿童谁是谁 CKD进展的最高风险将有助于指导那些最有可能从早期获益的人的治疗试验 治疗并避免那些进展风险较低的潜在治疗相关伤害的患者。两种潜力 出生后即可获得的CKD进展的生物标志物是肾实质面积(RPA)和 肾脏回声。RPA是肾脏最大纵长的总面积减去肾脏的面积 采集系统。RPA纠正了扩张的收集系统，这存在于许多CAKUT儿童中， 因此，比目前使用的肾脏长度测量更好地估计肾脏的功能面积。 RPA可以测量肾脏的功能储备，较小的区域与较低的肾单位质量相关 CKD进展的概率也更大。超声很容易评估肾脏的回声，并且可以 独立于RPA预测CKD进展。如果RPA估计了肾实质的数量， 回声测量残留肾单位肿块的质量。然而，因为肾脏回声是 目前主观评估和测量肾脏回声的方法还没有开发出来，其现状是 作为慢性肾脏病进展的临床生物标志物的实用性是有限的。这项拟议的研究将开发一种方法来 客观测量肾脏回声，然后利用儿童慢性肾脏病(CKiD)研究， 是否将RPA和肾脏回声作为儿童CKD进展的两个新的解剖学生物标志物 和卡库特一起。这些生物标志物的优点是，它们可以在CKD进展之前预测CKD进展 出现较晚的血清或尿液生物标志物，如最低值肌酐或蛋白尿，并可测量 出生后即刻无创伤性常规临床影像检查。我们将评估RPA作为预测指标的使用情况 肾功能下降的风险，并将开发一种自动方法来可靠和准确地测量肾脏 对100名CHOP上没有CKD和有CKD的儿童进行回声检测，然后使用ROC分析 验证这些影像生物标记物在CKiD登记的CAKUT儿童中的CKD进展。

PROJECT 2 ABSTRACT “DERIVATION AND VALIDATION OF IMAGING BIOMARKERS FOR CKD PROGRESSION” There is a need for biomarkers that can identify children with Congenital Anomalies of the Kidneys and Urinary Tract (CAKUT) early in life at high risk of future CKD progression. Early identification of children who are at highest risk of CKD progression would help guide trials of therapies for those most likely to benefit from early treatment and spare those patients at low risk of progression potential treatment-associated harms. Two potential biomarkers of CKD progression that are available immediately after birth are renal parenchymal area (RPA) and kidney echogenicity. RPA is the gross area of the kidney in maximal longitudinal length minus the area of the collecting system. RPA “corrects” for a dilated collecting system, which is present in many children with CAKUT, and thus better estimates the functional area of the kidney than the currently used measurement of kidney length. RPA may measure the functional reserve of the kidneys, with smaller areas associated with lower nephron mass and greater probability of CKD progression. Kidney echogenicity is easily assessed on ultrasound and may predict CKD progression independent of RPA. If RPA estimates the quantity of the kidney parenchyma, echogenicity measures the quality of the remaining nephron mass. However, because kidney echogenicity is currently subjectively assessed and ways to measure kidney echogenicity have not been developed, its present utility as a clinical biomarker of CKD progression is limited. This proposed research will develop a method to objectively measure kidney echogenicity and then, using the Chronic Kidney Disease in Children (CKiD) study, will validate RPA and kidney echogenicity as two novel anatomic biomarkers of CKD progression among children with CAKUT. The advantages of these biomarkers are that they may predict CKD progression prior to the appearance of later serum or urine biomarkers, such as nadir creatinine or proteinuria, and can be measured non-invasively immediately after birth on routine clinical imaging. We will evaluate the use of RPA as a predictor of kidney function decline, and will develop an automated method to reliably and accurately measure kidney echogenicity among a cohort of 100 children without and with CKD at CHOP, and then will use ROC analysis to validate these imaging biomarkers of CKD progression among children with CAKUT enrolled in CKiD.