Using Intradialytic Blood Pressure Slopes to Guide Ultrafiltration in Hemodialysis Patients

与美国退伍军人相比，美国退伍军人患终末期肾病(ESRD)的风险更高 普通民众。患有终末期肾病的退伍军人维持性血液透析(HD)的发病率高得惊人 死亡率和住院率主要与心血管疾病有关。细胞外体积(ECV) 过量是导致心血管疾病和HD死亡率升高的主要因素 病人。在临床实践中，细胞外体积过剩仍然很难识别，标准是 临床环境中液体管理的方法包括任意的尝试和错误的尝试以去除液体 而不会引起血液动力学不稳定，如透析中的低血压。生物阻抗谱(BIS) 是评估ECV的一个有用的研究工具；然而，它在常规实践中并不可行，而且数据很少 关于它的使用如何影响中期和艰难的临床结果。有一种未得到满足的需求，需要一种方法来解决 指导临床实践中的超滤，以降低ECV和其他死亡率结果为目标 以及最大限度地减少透析中的低血压。这项研究的长期目标是开发一种更精确的、 针对患者的液体管理方法将在旨在降低死亡率的大型临床试验中进行测试 高清老兵。这个项目的总体目标是利用我们新颖的、针对患者的超滤 在一项以死亡危险因素为主要结果的临床试验中，算法作为干预。中环 假设是根据个别患者透析中的血液前瞻性地开出超滤处方 最近治疗的压力斜率(IBPS)在减少动态血液方面优于标准护理 在不增加透析中低血压风险的情况下，增加压力和体外循环。目标一号将使用非盲目的、可控的 一项随机临床试验，以证明基于IBPS的超滤方与 标准的临床实践。每个月，IBPS组的最新超滤处方将是 根据最新的治疗数据确定。主要结果将是平均收缩压的变化 4个月后进行44小时动态血压监测。其他结果将包括1)HD后的变化 用多频生物阻抗谱测定ECV/体重，2)HD后全外周的变化 使用无创性心输出量监测仪的阻力指数，以及3)组间比较 透析中低血压和透析中症状的发生率。目标2将涉及横截面分析 除了连续参加额外的高血压HD外，目标1受试者的基线数据 病人。除了AIM 1的测量外，受试者还将在非胸部超声心动图检查 HD日测量左心室射血分数作为收缩功能、二尖瓣流入的度量 二尖瓣环运动速度作为舒张期功能的量度，以及左心室重量指数。混合线性 模型将用于确定这些指标如何独立地影响 ECV/体重和IBPS。IBPS和ECV/体重之间的关联强度将为 确定每三分位数内收缩和舒张期功能障碍的分布。最后，将会有一个 评价基于超声心动图的指标如何影响透析中低血压的可能性 在控制ECV/体重的同时进行前瞻性随访。如果成功，这项研究将为肾病学家提供 通过一种易于实施的个性化方法为HD退伍军人提供安全的液体管理 减少ECV过剩和相关的死亡风险因素。因为目前还不存在任何方法，所以这可能 立即改变处理患有终末期肾病的退伍军人的临床实践。长期影响将是 有机会利用生成的数据设计一项大型多中心试验，直接对此进行评估 干预对退伍军人终末期肾病HD病死率的影响观察到的血压下降可以 可用于确定预期死亡率，而超声心动图数据可用于确定表型 可能需要考虑纳入/排除标准的患者的比例。

United States Veterans have disproportionately higher risk for end stage renal disease (ESRD) compared to the general population. Veterans with ESRD on maintenance hemodialysis (HD) suffer from alarmingly high mortality rates and hospitalizations mainly related to cardiovascular disease. Extracellular volume (ECV) excess is a primary contributing factor to cardiovascular disease and the heightened mortality rate in HD patients. Extracellular volume excess remains difficult to identify in clinical practice, and the standard approach to fluid management in the clinical setting involves arbitrary trial and error attempts to remove fluid without invoking hemodynamic instability such as intradialytic hypotension. Bioimpedance spectroscopy (BIS) is a useful research tool for assessing ECV; however, it is not feasible in routine practice, and there is little data on how its use affects intermediate and hard clinical outcomes. There is an unmet need for an approach to guide ultrafiltration in clinical practice that addresses both reduction of ECV and other mortality outcomes as well as minimization of intradialytic hypotension. The long-term goal of this study is to develop a more precise, patient-specific fluid management approach to be tested in a large clinical trial aimed at reducing mortality in Veterans on HD. The overall objective of this project is to utilize our novel, patient-specific ultrafiltration algorithm as an intervention in a clinical trial using mortality risk factors as the primary outcomes. The central hypothesis is that prescribing ultrafiltration prospectively based on an individual patient’s intradialytic blood pressure slopes (IBPS) from recent treatments is superior to standard care at reducing ambulatory blood pressure and ECV without increasing risk for intradialytic hypotension. Aim 1 will use an un-blinded, controlled randomized clinical trial to demonstrate the effects of an IBPS-based ultrafiltration prescription compared to standard clinical practice. Each month, updated ultrafiltration prescriptions for the IBPS group will be determined based on the most recent treatment data. The primary outcome will be change in mean systolic 44-hour ambulatory blood pressure after 4 months. Other outcomes will include 1) change in post-HD ECV/body weight using multifrequency bioimpedance spectroscopy, 2) change in post-HD total peripheral resistance index using a non-invasive cardiac output monitor, and 3) between-group comparison of the frequency of intradialytic hypotension and intradialytic symptoms. Aim 2 will involve a cross sectional analysis of baseline data of subjects from Aim 1 in addition to consecutive enrollment of additional hypertensive HD patients. In addition to Aim 1 measurements, subjects will undergo transthoracic echocardiograms on a non- HD day to obtain measurements of left ventricular ejection fraction as a metric of systolic function, mitral inflow and mitral annulus velocities as a metric of diastolic function, and left ventricular mass index. Mixed linear models will be used to determine how these metrics independently influence the association between ECV/body weight and IBPS. The strength of the association between IBPS and ECV/body weight will then be determined within each tertile of the distributions of systolic and diastolic dysfunction. Finally, there will be an assessment of how the echocardiogram based metrics influence the likelihood of intradialytic hypotension with prospective follow up while controlling for ECV/body weight. If successful, this study will provide nephrologists with an easily-implemented, individualized approach to fluid management in Veterans on HD that safely reduces ECV excess and related mortality risk factors. Because no approach currently exits, this could immediately change clinical practice of managing Veterans with ESRD. The long term impact will be the opportunity to utilize the data generated to design a large, multi-center trial directly evaluating this intervention’s effect on mortality in Veterans with ESRD on HD. The observed reduction in blood pressure can be used to determine expected mortality, while the echocardiogram data can be used to determine phenotypes of patients that may need to be considered for inclusion/exclusion criteria.