Mechanisms of Increased Ambulatory Blood Pressure in Intradialytic Hypertension

描述(由申请者提供)：这份由NIH指导的以患者为导向的研究职业发展奖提案描述了一个为期5年的培训计划，长期目标是候选人发展成为一名独立的学术研究人员，专注于慢性和终末期肾脏疾病患者的高血压研究。候选人将在研究透析中高血压患者的动态血压和内皮细胞功能障碍的综合研究奖学金期间开发的临床研究的背景。职业发展目标是获得设计和实施前瞻性临床研究研究的技能，学习分析血液透析患者动态血压的统计模型，获得利用生物阻抗分析测量和解释心血管生理参数(包括细胞外水和血管阻力)的经验，并参与学术活动，促进TE过渡为独立研究人员。这些将被立即应用于研究细胞外体积和血管阻力介质如何影响传统透析高血压和血液透析对照组患者的动态血压。目的1采用病例对照设计，比较透析高血压患者和血液透析对照组患者细胞外水的差异。目的2将确定细胞外容量、血管阻力的血管收缩介质和血管阻力本身如何改变这两组的动态血压和动态血压斜率。在目标3中，候选人将获得设计和实施随机试验的经验，方法是比较卡维地洛和哌唑嗪对透析中高血压患者的动态血压、血管阻力和血管阻力介质的影响。候选人将在一名主要导师、三名共同导师(包括一名转化研究心脏病专家和一名生物统计学家)和一个在多个研究学科拥有广泛经验的研究咨询委员会的支持下发展这些技能。候选人和他的顾问位于德克萨斯大学西南医学中心，这是一个领先的学术医学中心，拥有年轻研究人员职业发展和尖端研究表现所需的大量体力和智力资源。作为临床科学系的临床研究学者，应聘者将利用众多课程和研究活动促进其职业生涯的全面发展。与候选人的长期职业目标一致，这项研究的发现可以扩大到一般血液透析患者的高血压研究。了解细胞外体积、血管阻力和动态血压之间的关系将为研究药物治疗如何影响血液透析患者的每个组成部分以及如何改善心血管结局提供机会。

DESCRIPTION (provided by applicant): This NIH Mentored Patient-Oriented Research Career Development Award proposal describes a 5 year training program with the long-term goal of the candidate developing into an independent academic investigator with a research focus in hypertension in patients with chronic and end-stage kidney disease. The candidate will build on a background in clinical research developed during a comprehensive research fellowship spent studying ambulatory blood pressure and endothelial cell dysfunction in patients with intradialytic hypertension. The career development objectives are to obtain skills in designing and conducting prospective clinical research studies, learn statistical models to analyze ambulatory blood pressure in hemodialysis patients, gain experience in measuring and interpreting cardiovascular physiologic parameters including extracellular water and vascular resistance utilizing bioimpedance analysis, and participate in scholarly activities to facilitate te transition into an independent investigator. These will be applied immediately to investigating how extracellular volume and mediators of vascular resistance affect ambulatory blood pressure in patients with intradialytic hypertension and hemodialysis controls. Aim 1 will use a case control design to compare differences in extracellular water in patients with intradialytic hypertension and hemodialysis controls. Aim 2 will determine how extracellular volume, vasoconstrictor mediators of vascular resistance, and vascular resistance itself modify ambulatory blood pressure and the ambulatory blood pressure slope in these two groups. In aim 3, the candidate will gain experience in designing and conducting a randomized trial by comparing the effects of carvedilol vs. prazosin on ambulatory blood pressure, vascular resistance, and mediators of vascular resistance in patients with intradialytic hypertension. The candidate will develop these skills with the support a primary mentor, 3 co-mentors (including one translational research cardiologist and one biostatistician), and a research advisory committee with extensive experience in multiple research disciplines. The candidate and his advisors are located at the University of Texas Southwestern Medical Center, a leading academic medical center with substantial physical and intellectual resources necessary for the career development of young investigators and the performance of cutting-edge research. The candidate will take advantage of numerous courses and research activities as a Clinical Research Scholar in the Department of Clinical Sciences that will promote the overall development of his career. Consistent with the candidate's long term career goals, the findings from this study can be broadened to studying hypertension in hemodialysis patients in general. Understanding the relationship between extracellular volume, vascular resistance, and ambulatory blood pressure will provide the opportunity to investigate how pharmacologic therapies affect each component and how this can improve cardiovascular outcomes in hemodialysis patients.