Investigating the Significance of Nocturnal Blood Pressure Patterns in Children with Chronic Kidney Disease

调查慢性肾病儿童夜间血压模式的意义

• 批准号: 10523743
• 负责人: Christine Bakhoum
• 金额: $ 19.17万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10523743
• 关键词: Investigating; Significance; Nocturnal; Blood; Pressure

PROJECT SUMMARY This is an initial submission of a K23 application by Dr. Christine Bakhoum, under the mentorship of Dr. Joachim Ix at the UC San Diego. Through this proposal, Dr. Bakhoum intends to establish herself as an independent investigator studying blood pressure (BP) patterns in pediatric chronic kidney disease (CKD). Candidate: Dr. Bakhoum’s training objectives include; 1) become proficient in the research applications of pediatric ambulatory blood pressure monitoring (ABPM) data, 2) develop skills in advanced biostatistical methods, 3) acquire expertise in pediatric clinical trial design and implementation, and 4) advance her professional development. Dr. Bakhoum will accomplish these objectives through mentorship, coursework, and participation in workshops and steering committees. She has assembled a multidisciplinary team of scientists including her primary mentor Dr. Joachim Ix, an expert in clinical trials in CKD, Dr. Dena Rifkin, a leader in hypertension and the application of ABPM, Dr. Adriana Tremoulet, a pediatric clinical trialist, and Dr. Ronit Katz, a PhD level biostatistician who works closely with her mentoring team. Research: A diagnosis of CKD in childhood portends high risk for cardiovascular disease (CVD) and mortality in early adult life. Thus, identifying modifiable risk factors for progression to end-stage kidney disease (ESKD) is critical. In adults, ABPM data demonstrates that loss of the physiologic decrease in BP at night compared to daytime, or BP non-dipping, is associated with kidney function decline and CVD. While non-dipping is prevalent in children with CKD, the definition of dipping in pediatrics is arbitrary and adopted from the adult literature. Dr. Bakhoum’s preliminary work demonstrated that blunted nocturnal dipping may have adverse consequences (i.e. proteinuria), that the thresholds for these consequences may be different for systolic vs. diastolic BP, and that kidney sodium mishandling may play a role in the pathophysiology. She hypothesizes that nocturnal BP change is, in part, caused by impaired daytime sodium excretion, and is a modifiable risk factor for progression to ESKD in children with CKD. In Aim 1, Dr. Bakhoum will evaluate the association of nocturnal BP patterns with risk of ESKD in the Chronic Kidney Disease in Children (CKiD) study. In Aim 2, she will recruit a cohort of 85 children with CKD and evaluate the association of the ratio of daytime to nighttime sodium excretion with dipping patterns. Of this cohort, she will recruit 26 children with hypertension and non- dipping who will continue to Aim 3. In Aim 3, she will conduct a randomized crossover study to test whether nighttime administration of BP medications can restore nocturnal BP dipping in children with CKD. The results of this proposal will provide a new framework for the interpretation of nocturnal BP in children with CKD and will serve as a foundation for future clinical trials to investigate whether nighttime dosing of anti-hypertensive medications can improve clinical outcomes in this population.

项目摘要 这是克莉丝汀·巴克胡姆博士首次提交的K23申请，在博士的指导下。 加州大学圣地亚哥分校的Joachim IX。通过这一提议，Bakhoum博士打算将自己确立为一个 研究儿童慢性肾病（CKD）患者血压（BP）模式的独立研究者。 候选人：Bakhoum博士的培训目标包括：1）精通以下研究应用： 儿科动态血压监测（ABPM）数据，2）培养高级生物统计学技能 方法，3）获得儿科临床试验设计和实施的专业知识，4）推进她 专业发展。Bakhoum博士将通过导师制、课程和 参加讲习班和指导委员会。她组建了一个多学科的科学家团队 包括她的主要导师Joachim IX博士，CKD临床试验专家，Dena Rifkin博士， 高血压和ABPM的应用，儿科临床试验医师Adriana Tremoulet博士和Ronit博士 Katz博士是一名生物统计学家，与她的导师团队密切合作。 研究：儿童期CKD的诊断预示着心血管疾病（CVD）和死亡率的高风险 在成年早期。因此，确定进展为终末期肾病（ESKD）的可改变的风险因素 至关重要。在成人中，ABPM数据表明，与夜间血压下降相比， 白天血压下降或血压不下降与肾功能下降和CVD有关。虽然非浸渍是 在CKD儿童中普遍存在，儿科中对dipping的定义是任意的，并从成人中采用 文学Bakhoum博士的初步研究表明，迟钝的夜间浸渍可能会对 结果（即蛋白尿），这些结果的阈值对于收缩压vs. 舒张压和肾钠处理不当可能在病理生理学中起作用。她假设 夜间血压变化部分是由白天钠排泄受损引起的，是一种可改变的风险， CKD儿童进展为ESKD的因素。在目标1中，Bakhoum博士将评估 儿童慢性肾脏病（CKiD）研究中夜间BP模式与ESKD风险。在目标2中，她 将招募85名CKD儿童，并评估白天与夜间的比率与CKD的关系。 钠排泄呈下降模式。在这个队列中，她将招募26名患有高血压和非高血压的儿童。 谁将继续瞄准目标3。在目标3中，她将进行一项随机交叉研究，以测试 夜间服用降压药物可以恢复CKD儿童夜间血压下降。结果 该提案的一部分将为解释CKD儿童的夜间血压提供一个新的框架， 将作为未来临床试验的基础，以研究夜间服用抗高血压药物是否 药物治疗可以改善这一人群的临床结果。