Investigating strategies to reduce fluid-related complications among hemodialysis patients

项目摘要/摘要 这个K23导师职业发展奖提案的目的是为詹妮弗·E·弗莱斯提供， 医学博士，公共卫生硕士，有保护的时间和资源，使她能够继续进行所需的额外培训，以达到 她的长期目标是成为一名独立的、以病人为导向的调查员。Flythe博士是一名获得董事会认证的 北卡罗来纳大学(UNC)教堂山分校的肾病学家。她的研究重点是流体 维持性血液透析患者的管理。透析患者体验极高 导致健康相关生活质量差和高生活质量的心血管并发症发生率 医疗保健成本。流体相关因素是造成这些不利结果的关键因素。更大的流体增益 在两次治疗之间，可以在透析过程中更快地去除液体(超滤，UF)。快速UF费率是 与透析中的低血压、反应性液体栓致的慢性容量扩张和未能 达到目标体重，以及其他不良的临床结果。创新和患者可接受的方法 为了改善结果，需要减少与UF相关的伤害。 K23奖项的支持将使Flythe博士实现以下目标：1)调查 开始透析的患者停止利尿剂(与继续利尿剂)的心血管风险比较；2) 研究超滤与传统透析在减少心血管疾病方面的效果。 相关的HD并发症；3)获得新的流行病学和临床试验研究技能；以及4)获得专业知识 对心血管结果的影响。为了实现这些目标，Flythe博士将研究 透析开始后利尿剂停止(与继续)在有透析前病史的偶发透析患者队列中的对比研究 使用透析利尿剂(目标1)。第二，她将对30名维持性HD患者进行交叉研究 超滤率升高的病史，以调查超滤谱与传统HD相比是否能降低低血压和 心肌缺血(目标2)。此外，她还将完成高级流行病学和 并参加有针对性的研讨会和系列研讨会，以扩大她的可比性 有效性研究技能。她将利用合并后的大型透析组织的独特透析队列 和Medicare管理索赔数据以及UNC拥有的门诊透析设施来完成 这些目标。拟议的工作很有可能产生重大的临床影响，因为 AIMS项目不仅将促进当前对减少UF相关危害的战略的理解，而且还将 提供在未来更大规模试验中针对目标的策略的初步数据。重要的是，提议的工作是现实的。 在获奖期内是可行的，并将使Flythe博士能够培养研究技能，产生初步数据， 建立协作关系，争夺R01资金。 Flythe博士将由她的联合小学导师M.Alan Brookhart博士、 北卡罗来纳大学吉林斯全球公共卫生学院的流行病学和罗纳德·J·福尔克，医学博士，教授 北卡罗来纳大学医学院的医学专业。布鲁哈特医生和福尔克医生在 流行病学和生物统计学(Brookhart)和国家肾脏病领导地位(Falk)将由Dr。 Flythe的科学咨询委员会：1)Alan Hinderliter，医学博士，北卡罗来纳大学医学副教授， 心脏病专家、超声心动图和心血管结果专家；2)史蒂文·M·布鲁内利，医学博士，MSCE， 达维塔临床医疗经济和结果研究副总裁兼医疗总监 透析结果研究和HD血流动力学方面的研究和专家；以及3)Laura Dember，医学博士， 宾夕法尼亚大学佩雷尔曼医学院医学教授和透析临床试验 专家。Flythe博士还将利用北卡罗来纳大学研究环境中可用的丰富资源 包括北卡罗来纳州医学院和公共卫生学院、北卡罗来纳州肾脏中心、北卡罗来纳州TraCS(北卡罗来纳州 临床和翻译科学奖)、塞西尔·G·谢普斯卫生服务研究中心和北卡罗来纳大学- 拥有卡罗莱纳州的透析室。Flythe博士提出的K23研究目标、导师团队、职业发展 计划和协作研究环境将催化她的科学生产力，并为她提供 在流行病学和临床试验方面的必要技能和经验，以成为独立的调查员和 未来透析研究的领导者。

PROJECT SUMMARY/ ABSTRACT The purpose of this K23 Mentored Career Development Award proposal is to provide Jennifer E. Flythe, MD, MPH with the protected time and resources to allow her to pursue the additional training needed to reach her long-term goal of becoming an independent patient-oriented investigator. Dr. Flythe is a board-certified nephrologist at the University of North Carolina (UNC) at Chapel Hill. Her research focuses on fluid management among maintenance hemodialysis (HD) patients. Dialysis patients experience exceedingly high rates of cardiovascular complications that contribute to both poor health-related quality of life and high healthcare costs. Fluid-related factors are critical contributors to these adverse outcomes. Greater fluid gain between treatments obligates faster fluid removal (ultrafiltration, UF) during dialysis. Rapid UF rates are associated with intradialytic hypotension, chronic volume expansion due to reactive fluid boluses and failure to achieve target weight, and other adverse clinical outcomes. Innovative and patient-acceptable approaches to reducing UF-related harm are needed to improve outcomes. The support of the K23 Award will allow Dr Flythe to achieve the following objectives: 1) investigate the comparative cardiovascular risks of diuretic cessation (versus continuation) among patients initiating HD; 2) investigate the comparative effectiveness of UF profiling vs. conventional dialysis in reducing cardiovascular- related HD complications; 3) gain new epidemiology and clinical trials research skills; and 4) acquire expertise in cardiovascular outcomes. To accomplish these objectives, Dr. Flythe will investigate the comparative risks of diuretic cessation (vs. continuation) after HD initiation in a cohort of incident HD patients with histories of pre- dialysis diuretic use (Aim 1). Second, she will perform a crossover study of 30 maintenance HD patients with histories of elevated UF rates to investigate whether UF profiling vs. conventional HD reduces hypotension and cardiac ischemia (Aim 2). Additionally, she will complete formal coursework in advanced epidemiology and clinical trials and participate in targeted workshops and seminar series to broaden her comparative effectiveness research skillset. She will leverage a unique dialysis cohort of merged large dialysis organization and Medicare administrative claims data as well as UNC-owned outpatient dialysis facilities to accomplish these aims. The proposed work has high potential to make a significant clinical impact, as completion of the project aims will not only advance the current understanding of strategies to reduce UF-related harm but also provide preliminary data on strategies to target in future, larger trials. Importantly, the proposed work is realistic and feasible within the award period and will allow Dr. Flythe to build research skills, generate preliminary data, create collaborative relationships, and compete for R01 funding. Dr. Flythe will be closely guided by her co-primary mentors, M. Alan Brookhart, PhD, Professor of Epidemiology at the UNC Gillings School of Global Public Health, and Ronald J. Falk, MD, Professor of Medicine at the UNC School of Medicine. Doctors Brookhart and Falk’s complementary strengths in epidemiology and biostatistics (Brookhart) and national nephrology leadership (Falk) will be augmented by Dr. Flythe’s scientific advisory committee: 1) Alan Hinderliter, MD, Associate Professor of Medicine at UNC, cardiologist and echocardiography and cardiovascular outcomes expert; 2) Steven M. Brunelli, MD, MSCE, Vice President and Medical Director of Health Economics and Outcomes Research at DaVita Clinical Research and expert in dialysis outcomes research and HD hemodynamics; and 3) Laura Dember, MD, Professor of Medicine at the University of Pennsylvania Perelman School of Medicine and dialysis clinical trial expert. Dr. Flythe will also draw upon the wealth of resources available in UNC’s research environment that include the UNC Schools of Medicine and Public Health, UNC Kidney Center, NC TraCS (home to UNC’s Clinical and Translational Science Award), Cecil G. Sheps Center for Health Services Research, and the UNC- owned Carolina dialysis units. Dr. Flythe’s proposed K23 research aims, mentorship team, career development plan, and collaborative research environment will catalyze her scientific productivity and provide her with the necessary skills and experience in epidemiology and clinical trials to become an independent investigator and future leader in dialysis research.