Discriminating Causes of Creatinine Change in Acute Heart Failure

急性心力衰竭肌酐变化的鉴别原因

基本信息

  • 批准号:
    10426052
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-10-01 至 2025-09-30
  • 项目状态:
    未结题

项目摘要

This is a resubmission of a Career Development Award (CDA) application by Dr. Nicholas Wettersten, mentored by Dr. Joachim Ix at the VA San Diego Health System (VASDHS). Through this proposal Dr. Wettersten intends to establish himself as an independent investigator studying acute heart failure (AHF), cardiorenal syndrome, and biomarkers. Candidate: Dr. Wettersten’s training objectives are designed to parallel his research project and provide skills required to lead an independent VA Merit Award upon completion of his CDA. These include: learning biostatistics for interpretation and analysis of multiple biomarkers concurrently, develop skills for designing and implementing clinical trials, and develop skills for scientific writing and independent lab management. Dr. Wettersten will achieve these objectives through coursework, workshops, and mentorship. His mentorship committee includes Dr. Joachim Ix (primary mentor), an expert in heart-kidney disease interaction, and co- mentors Dr. Kirk Hammond, an expert in clinical trials and translational research at the VASDHS, Dr. Patrick Murray, an expert in acute kidney injury and biomarkers at University College Dublin, and Dr. Florin Vaida, an expert biostatistician at UCSD. Research: AHF accounts for almost 1 million hospitalizations annually with significant morbidity and mortality. Approximately 350,000 Veterans suffer from heart failure with an annual mortality of almost 15%. Periods of AHF are an especially vulnerable period of heightened morbidity and mortality. Up to one-third of AHF patients will experience a rise in serum creatinine (sCr) with diuretics. This rise in sCr could be from true kidney injury or a benign reversible hemodynamic effect. Currently, clinicians have no means to distinguish these scenarios. Recently, a panel of urine kidney biomarkers of injury and dysfunction has been shown to discriminate the rise in sCr with intensive blood pressure lowering as hemodynamic vs. injury. This same process may occur in AHF, but this panel has not been tested in AHF. This proposal will leverage the Acute Kidney Injury N-gal Evaluation of Symptomatic Heart Failure Study (AKINESIS), a well-characterized study of 927 patients presenting with AHF and with repeat urine specimens available during treatment, as well as conduct an observational pilot study from admission into the post-discharge period of AHF patients admitted to the VASD hospital, to address the following specific aims: 1) To determine if admission values of urinary kidney tubule function and injury biomarkers associate with risk of adverse outcomes among AHF patients beyond admission sCr, 2) to determine whether changes in urinary kidney tubule function and injury biomarkers during hospitalization for AHF are more strongly associated with mortality and HF readmission than changes in sCr, and 3) to assess trajectories of urine kidney tubule function and injury biomarkers with changes in patient volume status during hospitalization and the first 30 days after discharge among AHF patients prospectively enrolled at the SDVA hospital. These findings will advance the understanding of renal function in AHF and will lead directly to randomized intervention studies to determine if modifying AHF treatment based on kidney biomarkers may improve re-hospitalizations and other outcomes in AHF patients.
这是Nicholas Wettersten博士重新提交的职业发展奖(CDA)申请, 由弗吉尼亚州圣地亚哥卫生系统(VASDHS)的Joachim IX博士指导。通过这个提议,博士。 Wettersten打算将自己确立为研究急性心力衰竭(AHF)的独立研究者, 心肾综合征和生物标志物。 候选人:Wettersten博士的培训目标旨在与他的研究项目平行,并提供技能 要求领导一个独立的VA优异奖后,他的CDA完成。其中包括:学习 同时解释和分析多种生物标志物的生物统计学,培养设计和 实施临床试验,并培养科学写作和独立实验室管理的技能。博士 Wettersten将通过课程,研讨会和导师实现这些目标。他的指导 委员会包括Joachim IX博士(主要导师),心脏-肾脏疾病相互作用的专家,以及 导师Kirk哈蒙德博士,VASDHS临床试验和转化研究专家,帕特里克博士 Murray是都柏林的急性肾损伤和生物标志物专家,Florin Vaida博士是一名 加州大学圣地亚哥分校的生物统计学专家 研究:AHF每年约有100万人住院,发病率和死亡率很高。 大约有35万退伍军人患有心力衰竭,年死亡率近15%。时期 急性心力衰竭是发病率和死亡率升高的特别脆弱时期。多达三分之一的AHF患者 使用利尿剂时,血清肌酐(sCr)会升高。sCr的升高可能是由于真正的肾损伤 或良性可逆的血液动力学效应。目前,临床医生没有办法区分这些情况。 最近,一组尿肾损伤和功能障碍的生物标志物已被证明可以区分 在sCr中,作为血流动力学与损伤,血压显著降低。同样的过程可能发生在 AHF,但该面板尚未在AHF中进行测试。该提案将利用急性肾损伤N-gal 症状性心力衰竭研究(AKINESIS)的评价,一项纳入927例患者的充分表征研究 在治疗期间出现AHF和重复尿液样本,以及进行 一项观察性初探性研究,对入住VASD的AHF患者从入院至出院后进行 目的:1)确定尿肾小管的入院值, 功能和损伤生物标志物与AHF患者入院后不良结局风险相关 sCr,2)以确定在尿中肾小管功能和损伤生物标志物的变化是否与尿中肾小管功能和损伤生物标志物的变化有关。 与sCr变化相比, 和3)评估尿肾小管功能和损伤生物标志物随患者变化的轨迹, AHF患者住院期间和出院后前30天的容量状态 在SDVA医院注册。这些发现将促进对AHF肾功能的理解, 直接导致随机干预研究,以确定是否修改基于肾脏的AHF治疗 生物标志物可以改善AHF患者的再住院和其他结果。

项目成果

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Nicholas Wettersten其他文献

Nicholas Wettersten的其他文献

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{{ truncateString('Nicholas Wettersten', 18)}}的其他基金

Biomarkers of Kidney Secretory Function for Discriminating Risk of Hyperkalemia
鉴别高钾血症风险的肾脏分泌功能生物标志物
  • 批准号:
    10727192
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
Discriminating Causes of Creatinine Change in Acute Heart Failure
急性心力衰竭肌酐变化的鉴别原因
  • 批准号:
    10595629
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
Discriminating Causes of Creatinine Change in Acute Heart Failure
急性心力衰竭肌酐变化的鉴别原因
  • 批准号:
    10116713
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
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