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: 10447162
• 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/10447162
• 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; Equilibrium; Excision; Fluid overload; Functional disorder; Funding; Goals; Hematocrit procedure; Hemodialysis; Homeostasis; Hybrids; Hypotension; Impairment; Inpatients; Institution; Intensive Care Units; Intervention Studies; Investigation; Ischemia; Kidney; Life; Linear Regressions; Link; Liquid substance; Maintenance; Master of Science; Measurement; Measures; Mediating; Mediation; Mediator of activation protein; 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; 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; epidemiology study; experience; heart function; hemodynamics; hypoperfusion; improved; interstitial; longitudinal analysis; multidimensional data; multidisciplinary; multiple chronic conditions; novel strategies; personalized approach; pressure; prevent; programs; prospective; rate of change; 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.

项目概要 每年有超过 1300 万人患上急性肾损伤 (AKI)，AKI 会增加发生慢性疾病的风险。 肾脏疾病、终末期肾脏疾病和死亡是一个重要组成部分。 管理需要透析的 AKI (AKI-D)，但安全实现最佳容量状态涉及一个微妙的过程 防止液体超负荷和避免循环系统受损之间的平衡。 条件使得 AKI 患者极易受到哪怕是轻微的血流动力学变化，并且常规 血压监测可能不足以检测微妙但具有临床意义的灌注变化 在血液透析期间连续监测全身或局部组织灌注是可行的。 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 的情况下 该提案的首要前提是优化液体管理。 在已经很脆弱的 AKI 人群中，需要 (1) 一个能够捕获个体化血流动力学的标记物 在整个血液透析治疗过程中对液体去除的反应，以及（2）更灵敏的检测技术 在 F32 奖项的资助下，王博士之前利用了连续血细胞比容监测。 (CHM) 在维持性血液透析治疗期间计算半瞬时血浆再填充率 (PRR)，是指超滤过程中从组织间隙重新充盈血管空间的速率。 通过这项 K23 提案，王博士将把 PRR 的研究扩展到 AKI 环境，并评估 具体来说，王博士将进行调解以评估血液透析期间的灌注。 使用大量维持性血液透析患者的数据进行分析，以确定是否存在 PRR 介导治疗相关因素对透析中低血压的影响（目标 1）； 在 AKI-D 患者队列中，她将连续血细胞比容监测与两种无创治疗相结合 技术 – 扩散相关光谱和扩散光学光谱 – 同时测量 改变全身灌注（目标 2）和脑灌注和氧合（目标 3）作为一种新方法 阐明血液透析明显和微妙的血流动力学效应背后的生理学。 她将使用床边测试将组织生理学的时空变化与认知变化联系起来 为了开展这项工作，王博士将利用正规的方法培训和实践经验。 她通过理学硕士学位获得了流行病学、研究设计和纵向分析方面的专业知识 通过她的 K23 职业发展计划，她将获得 (1) 设计技能。 并实施透析方面的前瞻性研究，(2) 研究急性护理结果的经验，以及 (3) 王博士在分析多维数据的先进方法方面拥有专业知识。 将有能力获得 R01 资金，继续努力实现开发小说的长期目标 这些方法将提高肾脏替代治疗的精确度并改善患者的治疗结果。