Research Project Core 2

研究项目核心2

• 批准号: 9768444
• 负责人: Gregory Edward Tasian
• 金额: $ 3.61万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9768444
• 关键词: 1 year old; 16 year old; 18 year old; Anatomy; Appearance; Area; Biological Markers; Birth; Cessation of life; Child; Child Care; Childhood; Chronic Kidney Failure; Clinical; Cohort Studies; Comorbidity; Congenital Abnormality; Creatinine; Derivation procedure; Disease Progression; Dysplasia; Early identification; Early treatment; End stage renal failure; Enrollment; Event; Future; Glomerular Filtration Rate; Growth; Hospitals; Infant; Intervention; Kidney; Length; Life; Measurement; Measures; Metabolic Bone Diseases; Methods; Nephrology; Nephrons; North America; Participant; Patients; Pediatric Hospitals; Philadelphia; Probability; Proteinuria; Receiver Operating Characteristics; Renal Replacement Therapy; Renal function; Research; Research Project Grants; Risk; Risk Factors; Serum; System; Therapy trial; Ultrasonography; Uncertainty; Urethra; Urinary tract; Urine; Validation; age group; base; boys; cardiovascular disorder risk; clinical biomarkers; clinical imaging; cohort; congenital anomaly; disorder risk; high risk; imaging biomarker; kidney cortex; longitudinal analysis; novel; outcome forecast; potential biomarker; prevent; symposium

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.

项目 2 摘要 “CKD 进展的成像生物标志物的推导和验证” 需要能够识别患有先天性肾脏和泌尿系统异常的儿童的生物标志物 早期识别未来 CKD 进展的高风险儿童。 CKD 进展的最高风险将有助于指导那些最有可能从早期治疗中受益的人的治疗试验 治疗并避免那些进展风险低的患者潜在的治疗相关危害有两种。 出生后立即可用的 CKD 进展的生物标志物是肾实质面积 (RPA) 和 肾脏回声强度是肾脏最大纵向长度的总面积减去肾脏的面积。 RPA“纠正”了许多患有 CAKUT 的儿童中存在的扩张的集合系统， 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，较小的面积与较低的肾单位质量相关 肾脏回声增强的可能性更大，可以通过超声轻松评估，并且可能会增加。 独立于 RPA 预测 CKD 进展 如果 RPA 估计肾实质的数量， 回声性衡量剩余肾单位质量的质量，但是，因为肾脏回声性是。 目前尚未开发出主观评估和测量肾脏回声性的方法，其目前 作为 CKD 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。 客观地测量肾脏回声性，然后利用儿童慢性肾脏病 (CKiD) 研究， 将验证 RPA 和肾脏回声性作为儿童 CKD 进展的两个新型解剖生物标志物 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。 随后出现血清或尿液生物标志物，例如最低肌酐或蛋白尿，并且可以进行测量 我们将在出生后立即通过常规临床影像进行非侵入性评估，以评估 RPA 作为预测指标的用途。 肾功能衰退，并将开发一种自动化方法来可靠、准确地测量肾功能 在 CHOP 中对 100 名未患 CKD 的儿童和患有 CKD 的儿童进行回声检查，然后使用 ROC 分析来确定 在参加 CKiD 的 CAKUT 儿童中验证这些 CKD 进展的影像生物标志物。