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.

摘要 血液透析（HD）人群存在认知障碍和脑缺血的严重负担 病理学，特别是小血管缺血性疾病伴白色物质疾病、腔隙和萎缩。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 其本身可能导致缺血性脑病理和相关的认知障碍。常规HD 与心肌功能障碍和血管内液体转移有关，这可能导致 HD期间的血压（BP）。为了在全身血压下降期间维持脑灌注， 下游脑微血管系统必须血管舒张，这是一种生理反应， 脑自动调节（CA）。同样的血管舒张反应发生在化疗刺激（即pCO 2），使用 脑血管反应性（CVR）机制。在HD人群中，动脉硬化，糖尿病， 高血压、炎症和血管钙化可能联合收割机损害这些脑血流 调节机制，并导致HD诱导的脑灌注不足和缺血的风险增加 BP下降。通过本R 03提案，我们将通过以下方法研究HD期间的脑血流调节： 测量HD队列中的CVR，并确定受损的CVR是否与更大的 HD期间的脑灌注。我们专注于CVR，因为它可以在老年人中安全，无创地测量。 与诱导低血压测量CA相比， 透析开始。在目标1中，我们测量了HD队列的CVR，并确定了包括肾脏疾病在内的风险因素 具体因素，降低CVR。我们将通过屏气诱导的高碳酸血症来测量CVR并量化 经颅多普勒检测脑血管血流速度的变化。在目标2中，我们将测量 CVR与HD期间脑灌注变化之间的相关性，以确定CVR是否可用于 确定接受HD治疗的脑缺血性疾病风险最高的患者。这将提供重要的 优化透析治疗以避免脑缺血性损伤所需的临床知识。最后，在目标3中， 将探讨CVR和CA之间的关系-控制脑血低至 看看小血管脑血管疾病是否可能是两种机制的共同基础病理， HD患者。这一建议将提高我们对血液透析患者脑血流调节的理解， 确定CVR是否可用于识别HD期间存在脑缺血性损伤风险的患者。结果将 告知R 01的设计，评价透析前肾病患者CVR随时间的变化， 与接受传统HD和其他透析方式（腹膜透析或夜间HD）的患者相比， 避免BP快速变化。这些信息可用于透析决策，以指导我们的高风险患者 患者接受与保留认知能力一致的透析治疗。