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

项目总结/摘要 本指导的以患者为导向的研究职业发展奖（K23）应用程序的目的是 支持我的短期职业目标，定量描述儿童的大脑结构和功能 使用磁共振成像（MRI）检测轻度至中度慢性肾病（CKD）患者。超过50%的 儿童CKD的病例是由于先天性（结构）异常，因此，诊断预示着生命- 需要常规护理的长期诊断。儿童CKD中肾功能下降的特征包括代谢性酸中毒， 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影响 对大脑发育的影响这是一个自然的延伸，患有晚期CKD的儿童有神经认知障碍的风险， 下降具体而言，尽管智力（IQ）总体上完好无损，但CKD儿童在以下方面表现出缺陷： 执行功能和学术成就。神经影像学研究利用了异质性样本 （包括终末期肾病），依赖计算机断层扫描。未发表儿科研究 已经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 在轻度至中度非肾小球CKD儿童患者中使用MRI进行的脑实质差异 与健康对照组相比，这将是第一项利用功能性MRI序列来表征大脑的研究。 pH值作为CKD相关代谢疾病的代表。这项研究将使用神经认知和实验室评估 结合儿童CKD人群中脑结构和功能的神经影像学相关性。我们 基于初步数据的假设，预测将观察到体积和白色物质差异， CKD参与者的小脑。这些差异将涉及完整的皮质-丘脑-小脑白色 与执行功能相关的物质束。我们将研究疾病负担对 小脑体积和白色物质的发展，通过评估一个横断面队列的儿童轻度至 与健康对照相比，中度CKD。了解儿童CKD的影响 对发育中的大脑的进展和严重程度将使人们对疾病的作用有更高的认识 进展，特别是代谢疾病，对儿童期神经发育结局的影响， 在CKD的整个生命周期中，为治疗和患者教育提供新的方法。我的临床工作 儿科肾脏病学和神经影像学的入门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。 建议的综合研究，导师，和教学培训计划，结合优秀的 研究环境在爱荷华州和场外导师从教师在儿童医院， 费城，将培养我的长期职业目标是成为一名独立的研究大脑的调查员 结构和功能的研究进展。

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.