Using Intradialytic Blood Pressure Slopes to Guide Ultrafiltration in Hemodialysis Patients

使用透析中血压斜率指导血液透析患者超滤

• 批准号: 10409650
• 负责人: Peter Noel Van Buren
• 金额: --
• 依托单位: VA NORTH TEXAS HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10409650
• 关键词: Achievement; Acute; Address; Adverse event; Affect; Algorithms; Blinded; Blood Pressure; Blood Vessels; Body Fluids; Body Weight; Cardiac; Cardiac Output; Cardiovascular Diseases; Cardiovascular system; Caring; Chronic; Clinical; Clinical Trials; Cross-Sectional Studies; Dangerousness; Data; Death Rate; Dialysis procedure; Echocardiography; End stage renal failure; Enrollment; Equilibrium; Excision; Exclusion Criteria; Expenditure; Fluid overload; Frequencies; Functional disorder; Future; General Population; Goals; Guidelines; Hemodialysis; Hospitalization; Hour; Hypotension; Impairment; Intervention; Kidney Diseases; Kidney Failure; Left Ventricular Ejection Fraction; Left Ventricular Mass; Linear Models; Liquid substance; Maintenance; Measurement; Measures; Methods; Monitor; Morbidity - disease rate; Multicenter Trials; Myocardial dysfunction; Outcome; Patients; Pattern; Peripheral Resistance; Phenotype; Physiology; Population; Practice Management; Prevalence; Randomized Controlled Clinical Trials; Research; Residual state; Risk; Risk Factors; Safety; Spectrum Analysis; Structure; Symptoms; Testing; Time; Ultrafiltration; United States; Update; Veterans; base; blood pressure reduction; body volume; clinical care; clinical practice; comparison group; cost; design; extracellular; follow-up; heart function; hemodynamics; high risk; hypertensive; indexing; individual patient; innovation; intervention effect; mortality; mortality risk; novel; patient population; personalized approach; primary outcome; prospective; randomized trial; recruit; routine practice; standard care; tool

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.

与普通人相比，美国退伍军人患终末期肾病 (ESRD) 的风险要高得多 接受维持性血液透析 (HD) 的终末期肾病 (ESRD) 退伍军人的患病率高得惊人。 死亡率和住院率主要与心血管疾病有关。 过量是导致心血管疾病和 HD 死亡率的主要因素 细胞外容量过多在临床实践中仍然很难识别，并且标准也很困难。 临床环境中的液体管理方法涉及任意尝试和错误尝试以去除液体 不会引起血流动力学不稳定，例如透析中低血压（BIS）。 是评估 ECV 的有用研究工具；但在常规实践中并不可行，且数据很少； 关于其使用如何影响中期和硬临床结果的问题尚未得到满足。 指导临床实践中的超滤，以解决 ECV 降低和其他死亡率结果的问题 以及最大限度地减少透析中低血压。这项研究的长期目标是开发更精确的、 患者特定的液体管理方法将在一项大型临床试验中进行测试，旨在降低死亡率 退伍军人 HD 该项目的总体目标是利用我们新颖的、针对患者的超滤。 算法作为临床试验的干预措施，使用死亡风险因素作为主要结果。 假设是根据个别患者的透析中血液前瞻性地开出超滤处方 最近治疗的压力斜率（IBPS）在减少动态血方面优于标准治疗 目标 1 将使用非盲法、受控方法。 随机临床试验证明基于 IBPS 的超滤处方与 每个月都会更新 IBPS 组的超滤处方。 根据最新的治疗数据确定主要结果是平均收缩压的变化。 4 个月后的 44 小时动态血压包括 1) HD 后的变化。 使用多频生物阻抗谱测量 ECV/体重，2) HD 后总外周血的变化 使用无创心输出量监测仪测量阻力指数，以及 3) 组间比较 透析期间低血压和透析期间症状的发生率将涉及横断面分析。 除了连续登记额外的高血压 HD 之外，目标 1 受试者的基线数据 除了目标 1 测量外，受试者还将接受非经胸超声心动图检查。 HD 日获取左心室射血分数测量值，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度量，以及左心室质量指数。 模型将用于确定这些指标如何独立影响之间的关联 ECV/体重和 IBPS 与 ECV/体重之间的关联强度为 最后，将在收缩期和舒张期功能障碍的分布的每个三分位数内确定。 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 如果成功，这项研究将为肾脏病学家提供前瞻性随访，同时控制 ECV/体重。 通过一种易于实施、个性化的方法对退伍军人进行 HD 液体管理，安全 由于目前尚无方法，因此这可能会减少 ECV 过量和相关的死亡风险因素。 立即改变管理患有 ESRD 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来设计大型多中心试验，直接评估这一点 干预对患有 HD 终末期肾病 (ESRD) 的退伍军人死亡率的影响 观察到的血压降低可以。 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。