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

摘要 基线肾功能减退在急性心力衰竭(AHF)患者中非常普遍，是 是导致不良临床结果的最强大的风险因素。急性肾功能与急性肾功能的关系 然而，下降和结果仍然存在争议，一些研究表明，估计的 肾小球滤过(EGFR)与较差的预后相关，但其他研究并非如此。他的目标是。 麦卡勒姆的建议是为了更好地了解在环境中发生的急性EGFR下降的机制 并研究急性EGFR下降与包括长期肾功能在内的预后的关系。 死亡率和急性出血热住院人数。总体假设是三个关键组成部分--拥堵， 心脏血流动力学和神经激素(NH)活性是急性EGFR的主要危险因素 急性EGFR下降与临床结果之间的关系需要解释 在这三个因素发生变化的背景下。为了审视这些关系，她的目标是 包括：1)塔夫茨医学中心收治的AHF患者的回顾分析 肺动脉(PA)导管(n=890)，重复测量充血和心脏血流动力学；2) 塔夫茨医学中心140名留置PA导管的AHF患者的预期登记 测定血浆NH活性的重复测量；3)采用多轨迹模拟开发 结合EGFR变化轨迹研究急性心肾综合征的临床表型 充血、心脏血流动力学和NH活性。职业发展计划结合了说教 培训纵向数据分析，包括关节建模和多轨迹建模，生物标志物 电子健康记录研究的方法论、介绍性信息学以及沉浸式和实践性 心脏血流动力学培训和未来的患者招募，所有这些都是在一名 一组经验丰富的肾病学家、心脏病专家和统计学家，他们在肾脏疾病的各个方面都有专门知识 CRS.麦卡勒姆博士的初步数据显示，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Mark Sarnak博士领导下的生产力记录。 她的共同导师将是耶鲁大学心力衰竭研究主任、心脏病专家杰弗里·泰斯塔尼博士 在CRS方面有专业知识的大学教授，曾与McCallum博士在几篇手稿上合作，并 将她纳入他的研究小组，并为她赞助了几次去他在耶鲁的研究实验室的旅行。使用 在这个K23奖项中，McCallum博士将在生物统计方法、数据集创建、CRS 病理生理学、生物标记物方法学、原始数据收集和前瞻性研究设计。总而言之， 完成这些目标将为McCallum博士提供CRS方面的专业知识，并为她提供工具 这是成功争取独立资金所必需的。

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.