cerebrovascular reactivity in adults on hemodialysis and association with intradialytic cerebral hypoperfusion

成人血液透析的脑血管反应性及其与透析中脑灌注不足的关系

• 批准号: 10431736
• 负责人: Dawn F. Wolfgram
• 金额: $ 11.7万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-20 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10431736
• 关键词: Adult; Affect; Age; Arteriosclerosis; Atrophic; Blood; Blood Flow Velocity; Blood Pressure; Blood Vessels; Brain; Brain Pathology; Cerebral Ischemia; Cerebrovascular Circulation; Cerebrovascular Disorders; Cerebrum; Clinical; Cognition; Cognitive; Complement; Decision Making; Development; Diabetes Mellitus; Dialysis patients; Dialysis procedure; Disease; Drops; Fluid Shifts; Goals; Hemodialysis; Homeostasis; Hypercapnia; Hypertension; Hypotension; Hypovolemia; Impaired cognition; Impairment; Inflammation; Injury; Intervention; Ischemic Brain Injury; Kidney Diseases; Knowledge; Lead; Lesion; Measures; Modality; Myocardial Stunning; Myocardial dysfunction; Outcome; Oxygen saturation measurement; Pathology; Pathway interactions; Patients; Perfusion; Peritoneal Dialysis; Physiological; Population; Process; Quality of life; Recurrence; Regulation; Renal dialysis; Reproducibility; Risk; Risk Estimate; Risk Factors; Stimulus; Structure; Systemic blood pressure; Testing; Time; Uremia; Vascular Diseases; Vascular calcification; Vasodilation; White Matter Disease; Work; arterial stiffness; base; calcium phosphate; cerebral hypoperfusion; cerebral ischemic injury; cerebral microvasculature; cerebrovascular; cognitive capacity; cognitive function; cohort; design; high risk; improved; indexing; ischemic lesion; middle cerebral artery; neuroimaging; novel; older patient; patient stratification; preservation; prevent; response; risk stratification; vascular risk factor

ABSTRACT The hemodialysis (HD) population carries a substantial burden of cognitive impairment and ischemic brain pathology, especially small vessel ischemic disease with white matter disease, lacunae, and atrophy. Risk of cognitive impairment in HD patients is twice that of peritoneal dialysis patients, suggesting the HD process itself may contribute to ischemic brain pathologies and the associated cognitive impairment. Conventional HD is associated with myocardial dysfunction and intravascular fluid shifts, which can lead to significant decline in blood pressure (BP) during the HD session. To maintain cerebral perfusion during decline in systemic BP the downstream cerebral microvasculature must vasodilate, a physiological response that occurs as part of cerebral autoregulation (CA). The same vasodilation occurs in response to chemo stimuli (i.e. pCO2) using cerebrovascular reactivity (CVR) mechanisms. In the HD population, increased arteriosclerosis, diabetes, hypertension, inflammation, and vascular calcification may combine to impair these cerebral blood flow regulatory mechanisms and lead to increased risk of cerebral hypoperfusion and ischemia during HD-induced decline in BP. Through this R03 proposal we will investigate cerebral blood flow regulation during HD by measuring CVR in an HD cohort and determining if impaired CVR is associated with greater risk of decline in cerebral perfusion during HD. We focus on CVR as it can be measured safely and non-invasively in older patients with vasculopathy—compared to inducing hypotension to measure CA—and can be done prior to dialysis initiation. In Aim 1, we measure CVR in an HD cohort and identify risk factors, including renal disease specific factors, for lower CVR. We will measure CVR with breath-hold induced hypercapnia and quantify the change in blood flow velocity through cerebral vessels using transcranial Doppler. In Aim 2, we will measure the association between CVR and change in cerebral perfusion during HD, to determine if CVR can be used to identify patients who are at greatest risk for cerebral ischemic disease on HD. This will provide important clinical knowledge needed to optimize dialysis therapy to avoid cerebral ischemic injury. Finally, in Aim 3 we will explore the relationship between CVR and CA—distinct mechanisms that control cerebral blood low—to see if small vessel cerebral vascular disease may be a common underlying pathology to both mechanisms in HD patients. This proposal will improve our understanding of cerebral blood flow regulation in HD patients, and determine if CVR can be used to identify patients at risk for cerebral ischemic injury during HD. The results will inform the design of an R01 evaluating CVR changes over time in pre-dialysis kidney disease patients and comparing to those on conventional HD and other dialysis modalities (peritoneal dialysis or nocturnal HD) that avoid rapid BP changes. This information could be used in dialysis decision-making to guide our high-risk patients to dialytic therapy that is concordant with preserving cognitive capacity.

抽象的 血液透析（HD）种群具有大量认知障碍和缺血性大脑的燃烧 病理学，尤其是小血管缺血性疾病，患有白质疾病，空白和萎缩。风险 HD患者的认知障碍是腹膜透析患者的两倍，表明HD过程 本身可能有助于缺血性脑病理和相关的认知障碍。常规高清 与心肌功能障碍和血管内液移位有关，这可能导致显着下降 高清疗程中的血压（BP）。在系统性BP下降期间保持脑灌注 下游脑微脉管系统必须血管舒张，这是一种物理反应，是作为一部分的一部分 大脑自动调节（CA）。使用化学刺激（即PCO2）发生相同的血管舒张 脑血管反应性（CVR）机制。在高清人群中，动脉硬化增加，糖尿病， 高血压，感染和血管计算可能会结合以损害这些脑血流 调节机制，导致HD诱导期间脑灌注和缺血的风险增加 BP的下降。通过此R03提案，我们将研究HD期间的脑血流调节 测量HD队列中的CVR，并确定CVR受损是否与更大的下降风险有关 高清期间的脑灌注。我们专注于CVR，因为它可以在较旧的情况下安全地进行测量 血管病的患者（应诱导低血压测量CA），并且可以在 透析计划。在AIM 1中，我们测量HD队列中的CVR并确定危险因素，包括肾脏疾病 针对较低CVR的特定因素。我们将用呼吸诱导的高碳酸盐测量CVR，并量化 使用Trancranial Doppler通过脑视频改变血流速度。在AIM 2中，我们将衡量 HD期间CVR与大脑灌注变化之间的关联，以确定CVR是否可以使用 鉴定出在HD上患有脑缺血性疾病风险最大的患者。这将提供重要的 优化透析治疗所需的临床知识以避免脑缺血性损伤。最后，在目标3中我们 将探索CVR和CA之间的关系 - 控制大脑血液低的机制 看看小血管脑血管疾病是否可能是两种机制的常见病理 高清患者。该建议将提高我们对高清患者脑血流调节的理解，以及 确定在HD期间，CVR是否可以用于识别有脑缺血性损伤风险的患者。结果将 告知R01的设计，该R01评估CVR随着时间的流逝而变化，肾脏前肾脏疾病患者和 与传统的HD和其他透析方式（腹膜透析或夜间高清）相比 避免快速的BP变化。这些信息可以用于透析决策中，以指导我们的高风险 与保留认知能力一致的透明疗法的患者。