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.

抽象的 基线降低的肾功能在急性心力衰竭（AHF）的患者中非常普遍，并且是一个 不良临床结果的最强大风险因素。急性肾功能之间的关联 然而，下降和结果仍然存在争议，一些研究表明，估计的急性下降 肾小球滤过（EGFR）与较差的结果相关，但其他研究则不相关。博士的目标 McCallum的建议是更好地了解急性EGFR的机制下降的机制。 AHF并检查急性EGFR下降与包括长期肾功能的结果有关， 死亡率和AHF住院。总体假设是，三个关键组成部分 - 国会， 心脏血流动力学和神经激素（NH）活性 - 急性EGFR的主要危险因素 下降，需要解释急性EGFR下降与临床结果之间的关系 在这三个因素变化的背景下。为了检查这些关系，她的目标将 包括1）对进入塔夫茨医学中心的患者的回顾性分析，需要 肺动脉（PA）导管（n = 890），用于重复的拥塞和心脏血流动力学措施； 2） 有140名带有留置PA导管的塔夫茨医学中心的患者的预期入学 测定重复测量血浆NH活性的测量； 3）采用多条件模型来开发 急性心脏综合征（CRS）的临床表型通过结合EGFR变化的轨迹， 拥塞，心脏血流动力学和NH活性。职业发展计划结合了教学 纵向数据分析中的培训，包括关节建模和多区域建模，生物标志物 方法论，电子健康记录研究的信息，以及沉浸和实用 在心脏血流动力学和潜在的患者招募方面的培训，都是在 经验丰富的肾病学家，心脏病学家和统计学家在各个方面具有专业知识 CRS。如McCallum博士的初步数据所示，成功完成这些目标是可行的 机构KL2资金以及她在主要导师马克·萨纳克（Mark Sarnak）博士的领导下的生产力记录。 她的同事将是耶鲁大学心脏病学家兼心力衰竭研究主管Jeffrey Testani博士 在CRS方面拥有专业知识，与McCallum博士合作的大学，并有几本手稿 将她纳入了他的研究小组，并赞助了她去耶鲁大学的研究实验室的多次旅行。和 这是K23奖，McCallum博士将接受广泛的生物统计学方法，数据集创建，CRS的培训 病理生理学，生物标志物方法论，主要数据收集和前瞻性研究设计。在汇总中， 这些目标的完成将为McCallum博士提供CRS的专业知识，并为她提供工具 成功竞争独立资金所必需的。