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: 10462812
• 负责人: Christine Bakhoum
• 金额: $ 19.31万
• 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/10462812
• 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 control; blood pressure elevation; blood pressure medication; 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.

项目摘要 这是克里斯汀·巴库姆（Christine Bakhoum）博士在Dr. Joachim IX在圣地亚哥分校。通过这项建议，巴库姆博士打算将自己确立为 研究血压（BP）模式的独立研究者在小儿慢性肾脏疾病（CKD）中的模式。 候选人：巴库姆博士的培训目标包括； 1）精通 小儿卧床血压监测（ABPM）数据，2）发展高级生物统计学的技能 方法，3）获得儿科临床试验设计和实施方面的专业知识，以及4）提高她 专业发展。 Bakhoum博士将通过指导，课程工作和 参加研讨会和指导委员会。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，领导者Dena Rifkin博士 高血压和ABPM的应用，儿科临床试管员Adriana Tremoulet博士和Ronit博士 卡兹（Katz）是一位博士学位生物统计学家，她与她的心理团队紧密合作。 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 在成年早期生活。这是确定可修改的风险因素，以进展为终阶段肾脏疾病（ESKD） 很关键。在成人中，ABPM数据表明，与 白天或非浸泡与肾功能下降和CVD有关。而非浸水是 在患有CKD儿童的儿童中，儿科浸入的定义是任意的，并从成年人中采用 文学。 Bakhoum博士的初步工作表明，卑鄙的夜间浸入可能有对手 后果（即蛋白尿），这些后果的阈值对于收缩期VS可能有所不同。 舒张bp和肾脏钠不良可能在病理生理学中发挥作用。她假设 夜间BP的变化部分是由白天钠排泄受损引起的，是一种可修改的风险 CKD儿童进展为ESKD的因素。在AIM 1中，Bakhoum博士将评估 夜间BP模式在儿童慢性肾脏疾病（CKID）研究中具有ESKD风险。在AIM 2中，她 将招募一组CKD的85名儿童，并评估白天与夜间的比例 钠排泄带有浸入模式。在这个队列中，她将招募26名患有高血压和非 - 浸入将继续目标3的人。在AIM 3中，她将进行一项随机跨界研究，以测试是否是否 BP药物的夜间管理可以恢复CKD儿童的夜间BP浸入。结果 该提案将为CKD儿童的夜间BP解释提供一个新的框架 将作为将来临床试验的基础 药物可以改善该人群的临床结果。