Relation between acute changes in kidney function with clinical outcomes among patients with heart failure

心力衰竭患者肾功能急性变化与临床结局的关系

• 批准号: 10590891
• 负责人: Wendy MCCALLUM
• 金额: $ 19.23万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10590891
• 关键词: Acute; Adoption; Biological Assay; Biological Markers; Biostatistical Methods; Blood specimen; Cardiac; Cardiorenal syndrome; Cardiovascular system; Catheters; Central venous pressure; Clinical; Clinical Management; Collaborations; Cues; Data; Data Analyses; Data Collection; Data Set; Development Plans; Electronic Health Record; Enrollment; Event; Functional disorder; Funding; Future; Glomerular Filtration Rate; Goals; Heart failure; Hospitalization; Hospitals; Immersion; Informatics; Institution; Intervention Studies; Joints; Left; Literature; Manuscripts; Measures; Medical center; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methodology; Modeling; Outcome; Pathway interactions; Patient Admission; Patient Recruitments; Patients; Plasma; Population; Productivity; Prospective Studies; Pulmonary artery structure; Renal function; Renin; Research; Research Design; Risk Factors; Side; Testing; Training; Universities; Ventricular; adverse outcome; arm; career development; clinical phenotype; epidemiology study; experience; functional decline; glomerular filtration; hemodynamics; high risk; improved; improved outcome; indexing; mortality; patient population; pressure; prognostic; prospective; targeted treatment; tool

ABSTRACT Baseline reduced kidney function is highly prevalent among patients with acute heart failure (AHF) and is one of the most powerful risk factors for adverse clinical outcomes. The association between acute kidney function declines and outcomes, however, remain controversial, with some studies showing acute declines in estimated glomerular filtration (eGFR) to be associated with worse outcomes but other studies not. The goal of Dr. McCallum’s proposal is to better understand the mechanisms of acute eGFR declines that occur in the setting of AHF and examine how acute eGFR declines are related to outcomes including long term kidney function, mortality and AHF hospitalizations. The overall hypothesis is that three key components—congestion, cardiac hemodynamics, and neurohormonal (NH) activity—are the primary risk factors for acute eGFR declines, and that the relation between acute eGFR declines and clinical outcomes needs to be interpreted within the context of changes in these three factors. In order to examine these relations, her Aims would include 1) retrospective analysis of patients admitted to Tufts Medical Center for AHF and requiring a pulmonary artery (PA) catheter (n=890) for repeated measures of congestion and cardiac hemodynamics; 2) prospective enrollment of 140 patients admitted to Tufts Medical Center for AHF with an indwelling PA catheter to assay for repeated measures of plasma NH activity; and 3) adoption of multi-trajectory modeling to develop clinical phenotypes of acute cardiorenal syndrome (CRS) by incorporating trajectories of eGFR change, congestion, cardiac hemodynamics, and NH activity. The career development plan incorporates didactic training in longitudinal data analysis including joint modeling and multi-trajectory modeling, biomarker methodology, introductory informatics for electronic health record research, as well as immersion and practical training in cardiac hemodynamics and prospective patient recruitment, all under the mentorship of an experienced group of nephrologists, cardiologists and statisticians with expertise in various aspects of the CRS. Successful completion of these aims is feasible, as shown by Dr. McCallum’s preliminary data under her institutional KL2 funding, as well her track record of productivity under her primary mentor Dr. Mark Sarnak. Her co-mentor will be Dr. Jeffrey Testani, a cardiologist and Director of Heart Failure Research at Yale University who has expertise in the CRS, has collaborated with Dr. McCallum on several manuscripts, and has incorporated her into his research group and sponsored several trips for her to his research lab at Yale. With this K23 award, Dr. McCallum will receive extensive training in biostatistical methods, dataset creation, CRS pathophysiology, biomarker methodology, primary data collection and prospective study design. In aggregate, completion of these aims will provide Dr. McCallum with expertise in the CRS and arm her with the tools necessary to successfully compete for independent funding.

摘要 基线肾功能降低在急性心力衰竭（AHF）患者中非常普遍，是一种严重的急性心力衰竭。 不良临床结果的最强大的风险因素。急性肾功能 然而，下降和结果仍然存在争议，一些研究显示， 肾小球滤过率（eGFR）与更差的结局相关，但其他研究没有。博士的目标。 McCallum的建议是为了更好地了解在这种情况下发生的急性eGFR下降的机制， 并研究急性eGFR下降如何与包括长期肾功能在内的结局相关， 死亡率和AHF住院率。总的假设是，三个关键组成部分-拥塞， 心脏血流动力学和神经激素（NH）活性是急性eGFR的主要风险因素 下降，并且需要解释急性eGFR下降与临床结局之间的关系 在这三个因素变化的背景下。为了研究这些关系，她的目标是 包括1）对塔夫茨医疗中心因AHF入院并需要 肺动脉（PA）导管（n=890），用于重复测量充血和心脏血流动力学; 2） 前瞻性入组140例因AHF入住塔夫茨医疗中心并留置PA导管的患者 测定血浆NH活性的重复测量;和3）采用多轨迹建模来开发 急性心肾综合征（CRS）的临床表型，包括eGFR变化的轨迹， 充血、心脏血流动力学和NH活性。职业发展计划包含了教育性的 纵向数据分析培训，包括联合建模和多轨迹建模，生物标志物 方法，电子健康记录研究的信息学介绍，以及沉浸和实践 心脏血流动力学培训和前瞻性患者招募，所有这些都在一位 一组经验丰富的肾病学家、心脏病学家和统计学家，他们在各个方面都有专业知识， CRS。成功地完成这些目标是可行的，正如麦卡勒姆博士在她领导下的初步数据所表明的那样。 机构KL 2的资金，以及她的生产力跟踪记录下她的主要导师马克Sarnak博士。 她的共同导师将是耶鲁大学心脏病专家兼心力衰竭研究主任杰弗里·泰斯塔尼博士 大学谁在CRS的专业知识，已与麦卡勒姆博士合作的几个手稿，并已 将她纳入他的研究小组，并赞助她几次前往他在耶鲁大学的研究实验室。与 在K23奖中，McCallum博士将接受生物统计方法，数据集创建，CRS 病理生理学、生物标志物方法学、原始数据收集和前瞻性研究设计。总的来说， 这些目标的完成将为麦卡勒姆博士提供CRS方面的专业知识，并为她提供工具 成功争取独立资金。