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

基本信息

批准号：
10611510
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
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-20 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10611510
关键词：
Adult Affect Age Arteriosclerosis Atrophic Blood Blood Flow Velocity Blood Pressure Blood Vessels Brain Brain Ischemia Brain Pathology Calcium Cephalic 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 Hypovolemics Impaired cognition Impairment Inflammation Injury Intervention Ischemia Ischemic Brain Injury Kidney Diseases Knowledge 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 cerebral hypoperfusion cerebral ischemic injury cerebral microvasculature cerebrovascular cognitive capacity cognitive function cohort design high risk improved indexing inorganic phosphate ischemic lesion middle cerebral artery neuroimaging novel older patient patient stratification preservation prevent response risk stratification vascular risk factor

项目摘要

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）人群承受着认知障碍和脑缺血的沉重负担病理学，特别是伴有白质疾病、腔隙和萎缩的小血管缺血性疾病的风险。 HD患者的认知障碍是腹膜透析患者的两倍，提示HD过程其本身可能会导致缺血性脑部病变和相关的认知障碍。与心肌功能障碍和血管内液体转移有关，这可能导致心肌功能显着下降 HD 期间的血压 (BP) 在全身血压下降期间维持脑灌注。下游脑微血管必须舒张血管，这是一种生理反应，作为使用化学刺激（即 pCO2）会发生相同的血管舒张。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共同损害这些脑血流调节机制并导致 HD 诱导期间脑灌注不足和缺血的风险增加通过这个 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 HD 下降的更大风险相关我们关注 HD 期间的脑灌注，因为它可以在老年人中安全、无创地测量。患有血管病变的患者——与诱导低血压来测量 CA 相比——并且可以在在目标 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。对于较低的 CVR，我们将测量屏气引起的高碳酸血症的具体因素，并量化 CVR。在目标 2 中，我们将使用经颅多普勒测量通过脑血管的血流速度的变化。 HD 期间 CVR 与脑灌注变化之间的关联，以确定 CVR 是否可用于确定 HD 中脑缺血性疾病风险最大的患者，这将提供重要的帮助。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，我们。将探讨 CVR 和 CA 之间的关系（控制脑血流低的独特机制）看看小血管脑血管疾病是否可能是这两种机制的共同潜在病理学 HD 患者的这项建议将提高我们对 HD 患者脑血流调节的了解，以及确定 CVR 是否可用于识别 HD 期间有脑缺血损伤风险的患者。告知 R01 的设计，评估透析前肾病患者的 CVR 随时间的变化，以及与传统 HD 和其他透析方式（腹膜透析或夜间 HD）相比避免血压快速变化。这些信息可用于透析决策，以指导我们的高风险。患者接受与保留认知能力相一致的透析治疗。