Cognitive Profiles and Neuroimaging Correlates in Mild to Moderate Pediatric Chronic Kidney Disease

项目摘要/摘要 这项以患者为导向的研究事业发展奖(K23)的目的是 支持我的短期职业目标，即定量描述儿童的大脑结构和功能 使用磁共振成像(MRI)检查轻至中度慢性肾脏病(CKD)。超过50%的人 儿童慢性肾脏病的病例是由于先天性(结构)异常，因此，诊断预示着生命- 长期诊断需要常规护理。儿童慢性肾脏病肾功能减退的特点包括代谢性酸中毒， 心血管疾病、生长不良和贫血--所有这些都可能产生有害的、多因素的影响 在发育中的大脑上。患有晚期CKD的儿童有神经认知的风险，这是一个自然的延伸 拒绝。具体地说，尽管智力(IQ)基本完好，但CKD儿童在 执行职能和学业成就。神经成像研究利用了不同种类的样本 (包括终末期肾病)，依靠计算机断层扫描。没有已发表的儿科研究 应用了定量结构或功能神经成像技术。我们将量化结构和白色 轻、中度非肾小球CKD儿童CKD的MRI脑实质差异 与健康对照组相比，这将是第一次利用功能磁共振序列来表征大脑的研究 PH可作为CKD相关代谢性疾病的代用品。这项研究将使用神经认知和实验室评估 结合神经成像研究儿童慢性肾脏病患者的大脑结构和功能。我们的 基于初步数据的假设，预测体积和白质的差异将在 CKD患者的小脑。这些差异将涉及完整的皮质-丘脑-小脑白质。 与执行功能相关的物质轨迹。我们将调查疾病负担的“剂量”效应 通过评估轻度到中度以下儿童的横断面队列，评估小脑体积和白质发育 与健康对照组相比，慢性肾脏病中度。对儿童慢性肾脏病影响的认识 发育中的大脑的进展和严重程度将使人们更好地认识到疾病的作用 进展，特别是代谢疾病对儿童和儿童神经发育结果的影响 在CKD的整个生命周期中提供治疗和患者教育的新方法。我在中国的临床工作 儿科肾病学和神经成像的介绍性工作为实现这些目标奠定了坚实的基础。 目标。在复杂的神经成像方法、神经发育和统计学方面的进一步培训是必要的。 拟议的综合研究、指导和教学培训计划，与杰出的 爱荷华大学的研究环境和爱荷华州儿童医院教职员工的非现场指导 费城，将培养我长期的职业目标，成为一名研究大脑的独立研究员 儿童慢性肾脏病的结构和功能。

Project Summary/Abstract The purpose of this Mentored Patient-Oriented Research Career Development Award (K23) application is to support my short-term career objective of quantitatively characterizing brain structure and function in children with mild to moderate chronic kidney disease (CKD) using magnetic resonance imaging (MRI). Over 50% of all cases of pediatric CKD are due to congenital (structural) anomalies, and as such, the diagnosis portends a life- long diagnosis requiring routine care. Features of renal decline in pediatric CKD include metabolic acidosis, cardiovascular disease, poor growth, and anemia—all of which may have a deleterious, multifactorial impact on the developing brain. It is a natural extension that children with advanced CKD are at risk for neurocognitive decline. Specifically, despite generally intact intelligence (IQ), children with CKD demonstrate deficits in executive function and academic achievement. Neuroimaging research has utilized heterogenous samples (including end-stage renal disease) with reliance on computerized tomography. No published pediatric studies have applied quantitative structural or functional neuroimaging techniques. We will quantify structural and white matter brain differences using MRI in pediatric CKD patients with mild to moderate, non-glomerular CKD compared to healthy controls; it will be the first study to utilize functional MRI sequences to characterize brain pH as a proxy of CKD-related metabolic disease. The study will use neurocognitive and laboratory assessment in conjunction with neuroimaging correlates of brain structure and function in the pediatric CKD population. Our hypotheses, based on preliminary data, predict volumetric and white matter differences will be observed in the cerebellums of CKD participants. These differences will involve integral cortico-thalamic-cerebellar white matter tracts associated with executive function. We will investigate a “dosage” effect of disease burden on cerebellar volume and white matter development by evaluating a cross-sectional cohort of children with mild to moderate CKD in comparison to healthy controls. Understanding the influence of pediatric CKD progression and severity on the developing brain will allow enhanced awareness of the role of disease progression, specifically metabolic disease, on neurodevelopmental outcomes in childhood and inform new approaches to treatment and patient education across the CKD lifespan. My clinical work in pediatric nephrology and introductory work with neuroimaging have laid a solid foundation for achieving these goals. Further training is necessary in sophisticated neuroimaging methods, neurodevelopment, and statistics. The proposed integrated research, mentorship, and didactic training programs, combined with the outstanding research environment at the University of Iowa and off-site mentorship from faculty at Children's Hospital of Philadelphia, will foster my long-term career objective to be an independent investigator studying brain structure and function in pediatric CKD.