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Macrovascular and Microvascular Response to Fluid Removal during Hemodialysis for Acute Kidney Injury

急性肾损伤血液透析期间液体去除的大血管和微血管反应

基本信息

批准号：
10869090
负责人：
Hao Wang
金额：
$ 7.49万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10869090
关键词：
Achievement Acute Renal Failure with Renal Papillary Necrosis Advanced Development Adverse effects Affect Age Attention Award Bedside Testings Blood Pressure Monitors Blood Vessels Cardiac Output Cerebrovascular Circulation Cerebrum Cessation of life Chronic Kidney Failure Clinical Cohort Studies Complex Complication Critical Illness Data Data Set Degree program Development Development Plans Devices Dialysis procedure Diffuse End stage renal failure Epidemiologic Methods Epidemiology Equilibrium Excision Fluid overload Functional disorder Funding Goals Hematocrit procedure Hemodialysis Homeostasis Hospitalization Hybrids Hypotension Impairment Inpatients Institution Intensive Care Units Intervention Studies Investigation Ischemia Kidney Kidney Diseases Life Linear Regressions Link Liquid substance Maintenance Master of Science Measurement Measures Mediating Mediation Mediator Mentors Methodology Methods Modality Modeling Monitor Myocardial Stunning Observational Study Operative Surgical Procedures Optics Organ Outcome Outcome Study Outpatients Oxygen Participant Patient-Focused Outcomes Patients Perfusion Persons Physiology Plasma Population Positioning Attribute Postoperative Period Predisposition Prospective Studies Prospective cohort Prospective, cohort study Reaction Time Recovery Renal Replacement Therapy Renal dialysis Research Design Research Personnel Risk Spectrum Analysis Statistical Models System Techniques Technology Testing Tissues Trail Making Test Training Treatment Factor Ultrafiltration Venous Work acute care adverse outcome career development cerebral oxygenation clinical epidemiology cognitive function cognitive testing cohort comorbidity design experience heart function hemodynamics hypoperfusion improved interstitial longitudinal analysis multidimensional data multidisciplinary multiple chronic conditions novel strategies personalized approach pressure prevent programs prospective response skills spatiotemporal treatment effect vigilance

项目摘要

Project Summary Over 13 million people develop acute kidney injury (AKI) each year. AKI increases the risk of incident chronic kidney disease, end-stage kidney disease, and death. Fluid removal (ultrafiltration) is an important component of managing dialysis-requiring AKI (AKI-D), but safe achievement of optimal volume status involves a delicate balance between preventing fluid overload and avoiding circulatory compromise. Acuity of illness and comorbid conditions render patients with AKI highly susceptible to even modest hemodynamic changes, and routine blood pressure monitoring may be inadequate to detect subtle, yet clinically meaningful, perfusion changes during hemodialysis. Continuous monitoring of systemic or local tissue perfusion is feasible using a variety of near-infrared optical technologies, but there has been limited application of these devices during hemodialysis particularly in the setting of AKI. The overarching premise of this proposal is that optimizing fluid management in an already vulnerable AKI population requires (1) a marker that captures an individualized hemodynamic response to fluid removal throughout hemodialysis treatments, and (2) more sensitive techniques to detect hypoperfusion. Funded by an F32 award, Dr. Wang previously leveraged continuous hematocrit monitoring (CHM) during maintenance hemodialysis treatments to calculate a semi-instantaneous plasma refill rate (PRR), which refers to the rate of refilling of the vascular space from the interstitial space during ultrafiltration. Through this K23 proposal, Dr. Wang will extend her investigations of PRR to the AKI setting and will evaluate novel approaches to assessing perfusion during hemodialysis. Specifically, Dr. Wang will perform mediation analysis using data from a large cohort of patients on maintenance hemodialysis to determine whether PRR mediates the effects of treatment-related factors on intradialytic hypotension (Aim 1); and, in a prospective cohort of patients with AKI-D, she will combine continuous hematocrit monitoring with two noninvasive techniques – diffuse correlation spectroscopy and diffuse optic spectroscopy ‒ to simultaneously measure changes in systemic perfusion (Aim 2) and cerebral perfusion and oxygenation (Aim 3) as a novel approach to elucidate the physiology underlying both overt and subtle hemodynamic effects of hemodialysis. Additionally, she will use bedside testing to link spatiotemporal changes in tissue physiology with changes in cognitive function. To conduct this work, Dr. Wang will utilize the formal methodologic training and practical experience in epidemiology, study design, and longitudinal analysis that she acquired through the Master of Science in Clinical Epidemiology Program. Through her K23 career development plan, she will gain (1) skills in designing and implementing prospective studies in dialysis, (2) experience studying outcomes in acute care, and (3) expertise in advanced methods for analyzing multidimensional data. Upon completion of this work, Dr. Wang will be well-positioned to obtain R01 funding to continue working toward her long-term goal of developing novel approaches that will increase the precision of renal replacement therapy and improve patient outcomes.

项目摘要每年有超过1300万人发生急性肾损伤（阿基）。阿基增加了慢性事件的风险肾病、终末期肾病和死亡。液体清除（超滤）是一个重要组成部分管理需要透析的阿基（AKI-D），但安全达到最佳容量状态涉及一个微妙的在防止液体过载和避免循环损害之间取得平衡。病情严重和共病这种情况使阿基患者非常容易受到即使是轻微的血流动力学变化的影响，并且常规血压监测可能不足以检测到细微但有临床意义的灌注变化在血液透析期间。使用各种方法连续监测全身或局部组织灌注是可行的。近红外光学技术，但这些设备在血液透析过程中的应用有限尤其是在阿基的情况下。该提案的首要前提是，在已经脆弱的阿基人群中，需要（1）捕获个体化血流动力学的标记物，对血液透析治疗中液体清除的反应，以及（2）更敏感的检测技术低灌注在F32奖的资助下，王博士以前利用连续红细胞压积监测 (CHM)以计算半瞬时血浆再灌注率 (PRR)指的是在超滤过程中从组织间隙再填充血管间隙的速率。通过这项K23提案，王博士将其PRR研究扩展到阿基环境，并将评估评估血液透析期间灌注的新方法。具体由王医生进行调解使用维持性血液透析患者的大型队列数据进行分析，以确定PRR是否介导治疗相关因素对透析中低血压的影响（目的1）;在一项前瞻性研究中，在AKI-D患者队列中，她将联合收割机连续红细胞压积监测与两种无创性技术-扩散相关光谱和扩散光学光谱同时测量全身灌注（目标2）和脑灌注和氧合（目标3）的变化作为一种新的方法，阐明血液透析的显性和隐性血液动力学效应的生理学基础。此外，本发明还她将使用床边测试将组织生理学的时空变化与认知功能的变化联系起来，功能为了进行这项工作，王博士将利用正规的方法学培训和实践经验在流行病学，研究设计，和纵向分析，她通过科学硕士学位，临床流行病学计划。通过她的K23职业发展计划，她将获得（1）设计技能并在透析中实施前瞻性研究，（2）研究急性护理结局的经验，以及（3）在分析多维数据的先进方法的专业知识。完成这项工作后，王博士将有能力获得R 01资金，继续朝着她开发小说的长期目标努力这些方法将提高肾脏替代治疗的精确度并改善患者的预后。