Using Intradialytic Blood Pressure Slopes to Guide Ultrafiltration in Hemodialysis Patients

美国退伍军人患终末期肾病（ESRD）的风险不成比例地高于 普通民众。接受维持性血液透析（HD）的ESRD退伍军人患有惊人的高 死亡率和住院率主要与心血管疾病有关。细胞外容积（ECV） 过量是导致心血管疾病和HD死亡率升高的主要因素 患者在临床实践中，细胞外体积过量仍然难以识别， 在临床环境中，液体管理的方法涉及任意试验和错误尝试以移除液体 而不会引起血液动力学不稳定性，例如透析中低血压。生物阻抗谱（BIS） 是评价ECV的有用的研究工具;然而，它在常规实践中不可行，并且数据很少 它的使用如何影响中间和硬临床结果。有一个未得到满足的需要， 在临床实践中指导超滤，解决ECV降低和其他死亡率结局， 以及透析中低血压的最小化。这项研究的长期目标是开发一种更精确， 患者特定的液体管理方法将在一项旨在降低死亡率的大型临床试验中进行测试， HD上的退伍军人本项目的总体目标是利用我们的新型患者特异性超滤 算法作为临床试验中的干预措施，使用死亡风险因素作为主要结局。中央 假设是基于个体患者的透析中血液前瞻性地规定超滤 最近治疗的压力斜率（IBPS）上级减少动态血液 血压和ECV，而不会增加透析中低血压的风险。目标1将使用非盲、对照 一项随机临床试验，旨在证明基于IBPS的超滤处方与 标准临床实践。每月将更新IBPS组的超滤处方 根据最近的治疗数据确定。主要结局将是平均收缩压的变化 44-4个月后的小时动态血压。其他结局将包括1）HD后的变化 使用多频生物阻抗谱的ECV/体重，2）HD后总外周血 使用无创心输出量监测仪测量阻力指数，以及3） 透析中低血压和透析中症状的频率。目标2将涉及一个横截面分析 除了连续入组额外高血压HD外，目标1受试者的基线数据 患者除目标1测量外，受试者还将在非超声心动图上接受经胸超声心动图检查。 HD日，以获得左心室射血分数的测量值作为收缩功能、二尖瓣流入量的指标 和二尖瓣环速度作为舒张功能的量度，以及左心室质量指数。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为 在收缩和舒张功能障碍的分布的每个三分位数内确定。最后，将有一个 评估基于超声心动图的指标如何影响透析中低血压的可能性， 前瞻性随访，同时控制ECV/体重。如果成功，这项研究将为肾脏病学家提供 采用易于实施的个性化方法对接受HD治疗的退伍军人进行液体管理， 降低ECV过量和相关死亡风险因素。由于目前没有任何方法， 立即改变管理ESRD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个大型的多中心试验，直接评估这一点 干预对接受血液透析的终末期肾病退伍军人死亡率的影响。观察到的血压降低可以 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。

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.