Advanced Kidney Health Monitoring in Persons Hospitalized with Heart Failure

心力衰竭住院患者的高级肾脏健康监测

基本信息

批准号：
10617831
负责人：
Michelle M Estrella
金额：
$ 70.09万
依托单位：
NORTHERN CALIFORNIA INSTITUTE/RES/EDU
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-30 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10617831
关键词：
Acute Address Adult Adverse event Affect Albuminuria Biological Markers Body Weight Changes Caring Clinical Clinical Data Clinical Trials Collection Congestive Heart Failure Creatinine Dimensions Discharge Plannings Diuresis Diuretics Dose Fibrosis Foundations Fright Goals Guidelines HIV Infections Health Health Status Heart failure Hospitalization Hospitals Hour Hypertension Impairment Individual Inflammation Injury Injury to Kidney Kidney Left Life Measures Medical Methods Monitor Natriuresis Natriuretic Peptides Nephrons Oral Outcome Patient Discharge Patients Pattern Persons Pharmacological Treatment Physiological Prediction of Response to Therapy Prognosis Readiness Renal function Renal tubule structure Residual state Resistance Resort Risk Role Safety Selection for Treatments Serum Severities Testing Therapeutic Thiazide Diuretics Treatment Efficacy Treatment Failure Tubular formation Visit Work adverse outcome biomarker panel cardiovascular health clinical care clinical decision-making clinical prognostic cohort common treatment cost diagnostic strategy effective therapy effectiveness evaluation follow-up hemodynamics high risk hospital readmission improved individual patient individualized medicine mortality mortality risk novel diagnostics patient response predict responsiveness prognostic tool prognostication reduce symptoms renal damage reparative capacity response risk minimization saluretic tissue injury tool treatment response treatment strategy

项目摘要

PROJECT SUMMARY Heart failure leads to >1.4 million hospitalizations annually in the U.S. During these acute decompensated heart failure (ADHF) hospitalizations, the kidneys’ health influences almost every aspect of management, including initial diuretic dosing, treatment intensification, and discharge planning. However, clinical reliance on serum creatinine, an insensitive, nonspecific and often misleading kidney biomarker, substantially contributes to suboptimal ADHF treatment. Although guidelines suggest that clinicians use the patient’s kidney function as an indicator for the initial diuretic dose, the creatinine is actually a poor predictor of diuretic response and clinicians must resort to “trial and error” in searching for each patient’s optimal dose. Further, although creatinine elevations during treatment commonly reflect beneficial effects, clinicians typically de-escalate diuresis from fear of worsening kidney damage. During discharge planning, this fear also drives clinicians to prescribe an oral diuretic dose that is too low, and to avoid beneficial therapies. These obstacles to ideal care culminate in delayed symptom relief, prolonged hospitalization, frequent readmissions, and high mortality risk. Given the kidney tubules’ central role in determining the effectiveness and safety of ADHF pharmacological treatment, clinicians need tools that capture kidney tubule health to optimize diuretic strategies, improve delivery of guideline-directed medical therapy, and minimize the risk for true kidney damage. In ambulatory settings, our team has demonstrated the remarkable ability of tubule health measures to detect kidney damage early, to reflect the kidneys’ response to treatment more accurately that creatinine, and to predict long-term outcomes. Early studies of a few tubule markers in ADHF show that they improve in proportion to diuretic response and have tremendous potential to change how kidney health is monitored during ADHF treatment. Given the central role of kidney health in ADHF treatment and prognosis, our overall goals are to fundamentally change how clinicians approach kidney health monitoring and clinical decision-making during ADHF treatment. To achieve these goals, we will capitalize on the well-characterized Mechanisms of Diuretic Resistance (MDR) Study, a cohort of patients hospitalized for ADHF who have undergone serial biospecimen collections timed to diuretic treatment throughout hospitalization with longitudinal follow-up for key clinical outcomes. We will measure a broad panel of kidney biomarkers that reflect tubule reabsorptive and secretory functions, injury, synthetic and reparative capacity, and tubulointerstitial inflammation and fibrosis. We will identify which tubule health measures most effectively: 1) predict treatment response to initial loop diuretic dosing and adjunctive diuretic therapy (Aim 1); 2) discern pseudo- from intrinsic kidney damage among patients with creatinine elevations during treatment (Aim 2); and 3) identify patients appropriate for discharge and distinguish their risks for subsequent adverse events (Aim 3). This project will lay the necessary groundwork for a clinical trial to test a kidney biomarker-guided ADHF treatment strategy.

项目摘要在这些急性失效期间，在美国，心力衰竭每年导致140万次住院心力衰竭（ADHF）住院，孩子的健康几乎影响了管理的各个方面，包括初始利尿剂，治疗强化和排出计划。但是，临床缓解血清肌酐，一种不敏感的，非特异性且经常具有误导性的肾脏生物标志物，大大贡献了次级ADHF治疗。尽管指南表明临床医生将患者的肾脏功能用作肌酐的初始利尿剂剂量的指标实际上是利尿反应和临床医生必须在寻找每个患者的最佳剂量时诉诸“反复试验”。虽然治疗期间肌酐升高通常反映了有益的影响，临床医生通常会降级 diuresis因担心担心肾脏损害。在出院计划中，这种恐惧还驱使临床医生到开出一个过低的口服利尿剂剂量，以免有益疗法。这些理想护理的障碍最终导致延迟的救济，长时间住院，频繁再入院和高死亡率风险。鉴于肾管在确定ADHF药物的有效性和安全性方面的核心作用治疗，临床医生需要捕获肾脏Tubele Health的工具来优化利尿剂，改善提供指导指导的医疗疗法，并最大程度地减少肾脏损害的风险。在卧床设置，我们的团队已经证明了Tubele健康措施检测肾脏损害的非凡能力早期，为了反映孩子对肌酐的治疗的反应，并预测长期结果。 ADHF中一些小管标记的早期研究表明，它们与利尿剂成比例改善反应并具有改变ADHF治疗期间肾脏健康的巨大潜力。鉴于肾脏健康在ADHF治疗和预后中的核心作用，我们的总体目标是从根本上改变临床医生如何处理肾脏健康监测和临床决策 ADHF治疗。为了实现这些目标，我们将利用利尿剂的良好特征机制抗药性（MDR）研究，一组经历了串行生物测定的ADHF住院的患者在整个住院期间进行利尿治疗的收集时间，并进行了纵向随访的关键临床结果。我们将测量一组反映小管的肾脏生物标志物功能，损伤，合成和修复能力以及纤维素间质感染和纤维化。我们将确定哪种小管健康测量最有效：1）预测对初始循环利尿剂的治疗反应给药和辅助利尿治疗（AIM 1）； 2）辨别伪 - 与内在的肾脏伤害治疗过程中肌酐升高的患者（AIM 2）； 3）确定适合出院的患者并区分他们随后发生不良事件的风险（AIM 3）。这个项目将奠定必要的临床试验测试肾脏生物标志物引导的ADHF治疗策略的基础工作。