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.

项目概要在美国，心力衰竭每年导致超过 140 万人住院。心力衰竭 (ADHF) 住院、肾脏健康几乎影响管理的各个方面，包括初始利尿剂量、强化治疗和出院计划，但仍取决于临床。血清肌酐是一种不敏感、非特异性且经常误导性的肾脏生物标志物，在很大程度上有助于尽管指南建议坚持者将患者的肾功能视为次优的 ADHF 治疗。作为初始利尿剂量的指标，肌酐实际上不能很好地预测利尿反应，然而，战士们必须通过“反复试验”来寻找每个患者的最佳剂量。治疗期间肌酐升高通常反映了有益效果，通常会降级由于担心肾脏损伤恶化而进行利尿在出院计划期间，这种恐惧也会强烈驱使。开出过低的口服利尿剂剂量，以避免有益治疗的这些障碍。最终导致症状缓解延迟、住院时间延长、频繁再入院和高死亡风险。鉴于肾小管在确定 ADHF 药理学有效性和安全性方面的核心作用治疗，奈特需要捕捉肾小管健康状况的工具来优化利尿策略，改善提供指南指导的药物治疗，并最大程度地降低门诊真正肾损伤的风险。在这种情况下，我们的团队展示了肾小管健康措施检测肾脏损伤的卓越能力早期，比肌酐更准确地反映肾脏对治疗的反应，并预测长期对 ADHF 中一些肾小管标志物的早期研究表明，它们的改善与利尿剂成比例。反应并具有改变 ADHF 治疗期间肾脏健康监测方式的巨大潜力。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肾脏健康监测和临床决策的方式为了实现这些目标，我们将利用利尿剂的明确机制。耐药性 (MDR) 研究，一组因 ADHF 住院且接受了系列生物样本检查的患者在整个住院期间按时进行利尿治疗，并对关键临床进行纵向随访我们将测量一系列反映肾小管重吸收和分泌功能的肾脏生物标志物。功能、损伤、合成和修复能力以及肾小管间质炎症和纤维化。确定哪种肾小管健康措施最有效：1) 预测对初始袢利尿剂的治疗反应剂量和辅助利尿治疗（目标 1）；区分伪肾损伤和内在肾损伤治疗期间肌酐升高的患者（目标 2）和 3）确定适合出院的患者；并区分后续不良事件的风险（目标 3）。测试肾脏生物标志物引导的 ADHF 治疗策略的临床试验奠定了基础。