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

项目总结 这是克里斯汀·巴克霍姆博士在克里斯汀·巴克霍姆博士的指导下提交的K23申请的初步申请。 加州大学圣地亚哥分校的约阿希姆九世。通过这项提议，Bakhoum博士打算将自己确立为 研究儿童慢性肾脏疾病(CKD)血压(BP)模式的独立研究员。 应聘者：Bakhoum博士的培训目标包括：1)精通 儿科动态血压监测(ABPM)数据，2)发展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方面的专业知识，4)推进HER 职业发展。Bakhoum博士将通过指导、课程学习和 参加研讨会和指导委员会。她组建了一个由多学科科学家组成的团队 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，儿科临床试验阿德里亚纳·特雷姆莱医生和罗尼特医生 Katz是一名博士级别的生物统计学家，她与她的指导团队密切合作。 研究：儿童时期被诊断为慢性肾脏病预示着心血管疾病(CVD)和死亡率的高风险 在成年初期。因此，确定进展为终末期肾病(ESKD)的可改变的危险因素 是至关重要的。在成年人中，ABPM数据表明，与夜间相比，夜间血压的生理性下降的消失 白天，或血压不下降，与肾功能下降和心血管疾病有关。而非浸泡是 在CKD的儿童中流行，儿科对浸泡的定义是随意的，从成人开始采用。 文学。Bakhoum博士的初步工作表明，钝化的夜间游泳可能会对 结果(即蛋白尿)，这些结果的阈值可能是不同的收缩压与 舒张压升高，肾脏钠处理不当可能在其病理生理机制中起一定作用。她假设 夜间血压变化在一定程度上是由白天钠排泄受损引起的，这是一种可以改变的风险。 慢性肾脏病儿童进展为ESKD的因素。在目标1中，Bakhoum博士将评估 儿童慢性肾脏病(CKiD)研究中夜间血压模式与ESKD风险的关系在《目标2》中，她 将招募85名患有慢性肾脏病的儿童，并评估白天和夜间比率的相关性 钠的排泄与浸泡的模式。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 在目标3中，她将进行一项随机交叉研究，以测试 CKD患儿夜间服用血压药物可恢复夜间血压下降。结果是 这一建议的提出将为解释慢性肾脏病儿童夜间血压提供一个新的框架。 将作为未来临床试验的基础，以调查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。

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.