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

摘要 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，尤指伴有脑白质病变、腔隙和萎缩的小血管缺血性疾病。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 其本身可能导致脑缺血病理和相关的认知功能障碍。传统高清 与心肌功能障碍和血管内液体移位有关，这可能导致 HD期间的血压(BP)。在体循环血压下降期间维持脑血流灌注 下游的大脑微血管必须扩张血管，这是一种生理反应，发生在 脑自动调节(CA)。同样的血管扩张发生在对化疗刺激(即二氧化碳分压)的反应 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诱导期间脑低灌注率和脑缺血风险增加 英国石油公司股价下跌。通过R03提案，我们将通过以下方式研究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 HD过程中的脑血流灌注。我们将重点放在CVR上，因为它可以在老年人中安全和非侵入性地测量 有血管病变的患者--与诱导低血压相比--测量CA--可以在 开始透析。在目标1中，我们在HD队列中测量CVR，并确定风险因素，包括肾脏疾病 特定因素，以获得较低的CVR。我们将测量屏气性高碳酸血症的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 血液透析期间CVR与脑血流灌注变化的关系，以确定CVR是否可用于 通过HD确定最有可能罹患脑缺血疾病的患者。这将提供重要的 优化透析治疗以避免脑缺血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--控制脑血流量低的不同机制 看看小血管脑血管疾病是否可能是这两种机制的共同基础病理 HD患者。这一建议将提高我们对HD患者脑血流调节的理解，并 确定是否可以使用CVR来确定HD期间有脑缺血损伤风险的患者。结果将会是 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 与传统透析和其他透析方式(腹膜透析或夜间透析)相比， 避免BP的快速变化。这一信息可以用于透析决策，以指导我们的高危人群 患者接受与保持认知能力相一致的透析治疗。

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.