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1300万人出现急性肾脏损伤（AKI）。 AKI增加了发生慢性事件的风险 肾脏疾病，末期肾脏疾病和死亡。液体去除（超滤）是重要组成部分 管理透析的AKI（AKI-D），但安全的最佳体积状态实现涉及一个微妙的 在防止流体超负荷和避免电路妥协之间取得平衡。疾病的敏锐度和合并症 条件使AKI患者高度容易受到适度的血液动力学变化和常规的影响 血压监测可能不足以检测微妙但临床上有意义的灌注变化 在血液透析期间。使用多种 近红外光学技术，但是在血液透析期间这些设备的应用有限 特别是在AKI的环境中。该提案的总体前提是优化的流体管理 在已经脆弱的AKI人群中，需要（1）捕获个性化血液动力学的标记 在整个血液透析治疗中对流体去除的反应，以及（2）更灵敏的技术检测 灌注不良。 Wang博士由F32奖资助，以前利用了继续进行血细胞比容的监测 （CHM）在维持血液透析治疗期间，以计算半触及等离子体重新填充速率 （PRR），它是指超滤期间从间质空间中重新填充血管空间的速率。 通过此K23提案，Wang博士将将PRR的调查扩展到AKI环境，并将评估 在血液透析过程中评估灌注的新方法。特别是王博士将进行调解 使用来自大量患者维持血液透析的数据的数据，以确定PRR是否是否 介导与治疗相关的因素对酯内性低血压的影响（AIM 1）；并且，在一个潜在的 她将与AKI-D患者队列，将连续的血细胞比容监测与两个无创 技术 - 弥漫性相关光谱和分散视光谱 - 同时测量 系统性灌注（AIM 2）和脑灌注和氧合（AIM 3）的变化作为一种​​新颖的方法 阐明了血液动力学的明显和微妙的血液动力学作用的生理。此外， 她将使用床头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，Wang博士将利用正式的方法论培训和实践经验 在流行病学，研究设计和纵向分析中，她通过科学硕士获得了 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）研究急性护理结果的经验；（3） 用于分析多维数据的高级方法的专业知识。完成这项工作后，王博士 将有很好的位置，以获得R01的资金，以继续朝着她发展新颖的长期目标努力 可以提高肾脏替代疗法的精度并改善患者预后的方法。