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

• 批准号: 10615858
• 负责人: Hao Wang
• 金额: $ 18.97万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 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/10615858
• 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

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1300万人患上急性肾损伤(AKI)。Aki增加了慢性事件的风险 肾病、终末期肾病和死亡。液体去除(超滤)是一个重要的组成部分 管理需要透析的AKI(AKI-D)，但安全地实现最佳容量状态涉及微妙的 在防止液体超载和避免循环损害之间取得平衡。疾病的敏锐性和共病 病情使AKI患者即使是轻微的血流动力学变化也非常容易发生，而且 血压监测可能不足以发现微妙但有临床意义的血流灌注变化。 在血液透析期间。连续监测全身或局部组织灌注是可行的，使用各种 近红外光学技术，但这些设备在血液透析中的应用有限 特别是在AKI的背景下。这项建议的首要前提是优化流体管理 在已经脆弱的AKI人群中，需要(1)捕捉个性化血流动力学的标志物 在整个血液透析治疗中对液体去除的反应，以及(2)更敏感的检测技术 低灌注率。在F32奖项的资助下，王博士之前利用连续的红细胞压积监测 在维持性血液透析治疗期间计算半瞬时血浆充盈率 (PRR)，指的是超滤过程中血管间隙从间质空间充盈的速率。 通过这项K23计划，王博士将把她对PRR的调查扩展到AKI环境，并将评估 评估血液透析期间血流灌注的新方法。具体来说，王博士将进行调解 使用大量维持性血液透析患者的数据进行分析，以确定PRR 调节治疗相关因素对传统透析中低血压的影响(目标1)； AKI-D患者队列，她将结合连续的红细胞压积监测和两个非侵入性 同时测量的技术--漫射相关光谱和漫射光学光谱 全身血流灌注的变化(目标2)和脑灌注和氧合(目标3)作为一种新的方法 阐明血液透析显性和微妙血流动力学效应的生理基础。另外， 她将使用床边测试将组织生理学的时空变化与认知的变化联系起来 功能。为了进行这项工作，王博士将利用正式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方面，她在年通过理科硕士获得 临床流行病学课程。通过她的K23职业发展计划，她将获得(1)设计技能 在透析中实施前瞻性研究，(2)在急性护理中体验研究结果，以及(3) 具有分析多维数据的高级方法方面的专业知识。在完成这项工作后，王博士 将处于有利地位，能够获得R01资金，继续朝着她开发小说的长期目标努力 将提高肾脏替代疗法的精确度并改善患者预后的方法。