Cardiac Complications of Hemodynamic Instability during Hemodialysis

 描述(由申请人提供)：这份有指导的职业发展奖重新提交申请将为芬尼安·麦克考斯兰博士(MB，MMSc)提供必要的资源、额外的培训和受保护的时间，以实现他成为一名独立的、以患者为导向的研究人员的长期目标。麦克考斯兰博士是哈佛医学院的医学讲师和布里格姆妇女医院的副内科医生。他概述了一项详细的培训计划，其中包括在哈佛公共卫生学院的授课课程、研究会议、领导力课程、负责任地开展研究的培训，以及在获奖期间在国际会议上发表演讲。这些将补充他强大的指导计划，世界级的咨询委员会，并建立在他之前获得医学硕士学位的人类调查培训的基础上。美国约有40万名终末期肾病(ESRD)患者接受维持性血液透析(HD)治疗。这些患者每年的死亡率高达20%，其中多达三分之一的患者在常规血液透析治疗期间出现严重低血压。这份K23指导职业发展奖重新提交建议书(PA-14-049)题为“血液透析期间血液动力学不稳定的心脏并发症”，旨在进行详细的检查，以严格调查透析中血压下降与不良心脏结果的作用。我们研究的最终目标是确定降低慢性血液透析(HD)患者心血管发病率和死亡率的方法。在目标1中，我们与透析监测(MID)研究的合作将促进通过植入式循环记录器的新使用来调查慢性HD患者SBP下降与心律失常负担之间的相关性的子研究。目标2将涉及创建一项针对门诊慢性血液透析患者的前瞻性队列研究。W将通过心脏MRI测量透析中SBP下降与心肌损伤生物标志物随时间的变化以及左心室射血分数变化之间的关系。在目标3中，我们将把我们先前观察报告中的发现转化为一项针对住院慢性血液透析患者的随机对照试验。我们将对140例慢性血液透析患者进行住院期间高透析液(142mmoL/L)与标准透析液(138mmolL)的单盲平行随机对照试验，检查透析中SBP下降的幅度作为主要结果。在此授权期结束时，Mc Causland博士将获得成功获得R01和/或R03资助的技能和专业知识，从而使他能够继续其至关重要的研究并培训未来的临床研究人员。

 DESCRIPTION (provided by applicant): This mentored career development award resubmission application will provide Dr. Finnian Mc Causland, MB, MMSc with the resources, additional training and protected time necessary to achieve his long-term goal of becoming an independent patient-oriented researcher. Dr. Mc Causland is an Instructor in Medicine at Harvard Medical School and an Associate Physician at Brigham and Women's Hospital. He has outlined a detailed training plan that includes didactic courses at Harvard School of Public Health, research conferences, leadership courses, training in the responsible conduct of research and presentations at international meetings during the award period. These will complement his strong mentoring plan, world-class advisory committee and build upon his prior training in human investigation for which he received a Masters in Medical Science degree. Approximately 400,000 patients in the United States are treated with life-sustaining hemodialysis (HD) for end stage renal disease (ESRD). These patients experience mortality rates of up to 20% per year, with up to one third experiencing significant hypotension during their regular hemodialysis treatments. This K23 Mentored Career Development Award resubmission proposal (PA- 14-049), entitled "Cardiac Complications of Hemodynamic Instability during Hemodialysis", aims to perform detailed examinations to critically investigate the role of intra-dialytic blood pressure decline with adverse cardiac outcomes. The ultimate goal of our research is to identify ways by which to reduce cardiovascular morbidity and mortality in chronic hemodialysis (HD) patients. In Aim 1, our collaborations with the Monitoring in Dialysis (MiD) study will facilitate sub-studies investigating associations of SBP decline with arrhythmia burden in chronic HD patients, via the novel use of implantable loop recorders. Aim 2 will involve creation of a prospective cohort study of patients initiating outpatient chronic HD. W will measure associations of greater intra-dialytic SBP decline with changes over time in biomarkers of myocardial injury and changes in left ventricular ejection fraction by cardiac MRI. In Aim 3 we will translate findings from our prior observational reports into a randomized controlled trial in hospitalized chronic HD patients. We will perform a single-blind, parallel grou randomized controlled trial of higher (142 mmol/L) vs. standard (138 mmol/L) dialysate sodium during hospitalization of 140 chronic HD patients, examining the magnitude of intra-dialytic SBP decline as the primary outcome. At the conclusion of this award period Dr. Mc Causland will have acquired the skills and expertise to successfully obtain R01 and/or R03 funding, thereby allowing him to continue his critically important research and to train future clinical investigatos.