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: 10283606
• 负责人: Christine Bakhoum
• 金额: --
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 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 2021-09-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10283606
• 关键词: 14 year old; Adopted; Adult; Albuminuria; Ambulatory Blood Pressure Monitoring; Antihypertensive Agents; Biostatistical Methods; Blood Pressure; Cardiovascular Diseases; Child; Childhood; Chronic Kidney Failure; Clinic; Clinical; Clinical Practice Guideline; Clinical Trials; Clinical Trials Design; Cross-Over Studies; Data; Development; Diagnosis; Dialysis procedure; Diastolic blood pressure; Disease Progression; Diuretics; Doctor of Philosophy; Dose; Educational workshop; End stage renal failure; Excretory function; Foundations; Functional disorder; Future; Hemorrhage; Hour; Hypertension; Impairment; Intake; Kidney; Kidney Diseases; Life; Literature; Measurement; Mentors; Mentorship; North America; Outcome; Pattern; Pediatrics; Pharmaceutical Preparations; Physiological; Play; Population; Proteinuria; Randomized; Renal function; Research; Research Personnel; Risk; Risk Factors; Role; Scientist; Severities; Sodium; Testing; Training; Work; adverse outcome; blood pressure medication; blood pressure regulation; cardiovascular disorder risk; cardiovascular health; circadian; cohort; disorder risk; early onset; high risk; improved; insight; modifiable risk; mortality; multidisciplinary; randomized trial; recruit; restoration; skills

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.

项目概要 这是 Christine Bakhoum 博士在 Dr. Christine Bakhoum 的指导下首次提交的 K23 申请。 加州大学圣地亚哥分校的约阿希姆九世 (Joachim Ix)。通过这项提议，Bakhoum 博士打算将自己打造为一名 研究儿童慢性肾病 (CKD) 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）精通研究应用 儿科动态血压监测 (ABPM) 数据，2) 培养高级生物统计技能 方法，3) 获得儿科临床试验设计和实施方面的专业知识，4) 提高她的能力 专业发展。 Bakhoum 博士将通过指导、课程作业和 参加研讨会和指导委员会。她组建了一支多学科的科学家团队 其中包括她的主要导师 Joachim Ix 博士（CKD 临床试验专家）、Dena Rifkin 博士（CKD 临床试验领域的领导者） 高血压和 ABPM 的应用，儿科临床试验师 Adriana Tremoulet 博士和 Ronit 博士 卡茨是一位博士级生物统计学家，与她的指导团队密切合作。 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）的可改变的危险因素 很关键。在成人中，动态血压监测 (ABPM) 数据表明，与白天相比，夜间血压生理下降消失 白天或血压不下降与肾功能下降和心血管疾病有关。虽然非浸渍是 CKD 儿童中普遍存在，儿科对“浸入”的定义是任意的，并且采用了成人的定义 文学。 Bakhoum 博士的初步研究表明，夜间沐浴迟钝可能会对身体产生不利影响。 后果（即蛋白尿），这些后果的阈值对于收缩压和收缩压可能不同。 舒张压，肾脏钠处理不当可能在病理生理学中发挥作用。她假设 夜间血压变化部分是由白天钠排泄受损引起的，并且是可改变的风险 CKD 儿童进展为 ESKD 的因素。在目标 1 中，Bakhoum 博士将评估以下关联： 儿童慢性肾脏病 (CKiD) 研究中夜间血压模式与 ESKD 风险的关系。在《目标 2》中，她 将招募 85 名 CKD 儿童组成的队列，并评估白天与夜间的比例之间的关联 钠排泄呈浸渍模式。在这个队列中，她将招募 26 名患有高血压和非糖尿病的儿童。 下降谁将继续目标 3。在目标 3 中，她将进行一项随机交叉研究，以测试是否 夜间服用血压药物可以恢复 CKD 儿童的夜间血压下降。结果 该提案将为解释 CKD 儿童夜间血压提供一个新框架， 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有效 药物可以改善该人群的临床结果。