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

• 批准号: 10337982
• 负责人: Michelle M Estrella
• 金额: $ 73.61万
• 依托单位: NORTHERN CALIFORNIA INSTITUTE/RES/EDU
• 依托单位国家: 美国
• 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/10337982
• 关键词: Acute; Address; Adult; Adverse event; Affect; Albuminuria; Biological Markers; Body Weight Changes; Caring; Clinical; Clinical Data; Clinical Trials; Collection; Congestive; Creatinine; Dimensions; Discharge Plannings; Diuresis; Diuretics; Dose; Fibrosis; Foundations; Fright; Goals; Guidelines; HIV Infections; Health; Health Status; Heart failure; Hospital Mortality; Hospitalization; Hospitals; Hour; Hypertension; Impairment; Individual; Inflammation; Injury; Injury to Kidney; Kidney; Lead; Left; Life; Measures; Medical; Methods; Monitor; Natriuresis; Natriuretic Peptides; Nephrons; Oral; Outcome; 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; Savings; 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; cohort; common treatment; cost; effective therapy; effectiveness evaluation; follow-up; hemodynamics; high risk; hormone therapy; hospital readmission; improved; individual patient; individualized medicine; mortality; mortality risk; novel diagnostics; patient response; predict responsiveness; prognostic tool; reduce symptoms; renal damage; reparative capacity; response; risk minimization; saluretic; tissue injury; tool; treatment response; treatment strategy

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 在美国，心力衰竭每年导致> 140万例住院治疗。 心脏衰竭（ADHF）住院治疗，肾脏的健康影响几乎每一个方面的管理， 包括初始利尿剂剂量、治疗强化和出院计划。然而，临床依赖于 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， 不理想的抗心衰治疗尽管指南建议临床医生使用患者的肾功能作为 作为初始利尿剂剂量的指标，肌酐实际上是利尿反应的不良预测因子， 临床医生必须采取“试错法”来寻找每个病人的最佳剂量。此外，虽然 治疗期间肌酐升高通常反映了有益效果，临床医生通常会降低 因担心肾损害加重而多尿。在出院计划期间，这种恐惧也促使临床医生 开口服利尿剂剂量太低，并避免有益的治疗。这些阻碍理想护理的因素 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。 考虑到肾小管在决定ADHF药理学有效性和安全性方面的中心作用， 治疗，临床医生需要的工具，捕捉肾小管健康，以优化利尿策略，改善 提供指南指导的药物治疗，并最大限度地减少真正的肾损伤的风险。非卧床 我们的团队已经证明了肾小管健康措施检测肾损伤的显着能力 早期，更准确地反映肾脏对治疗的反应，并预测长期 结果。早期对ADHF中一些小管标志物的研究表明，它们与利尿剂成比例地改善， 这一发现具有巨大的潜力，可以改变ADHF治疗期间监测肾脏健康的方式。 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在治疗过程中如何进行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， 耐药（MDR）研究，一项接受系列生物标本的ADHF住院患者队列 在整个住院期间定时收集利尿剂治疗，并对关键临床 结果。我们将测量一组广泛的反映肾小管重吸收和分泌的肾脏生物标志物 功能、损伤、合成和修复能力以及肾小管间质炎症和纤维化。我们将 确定哪种小管健康措施最有效：1）预测对初始袢利尿剂的治疗反应 剂量和连续性利尿治疗（目的1）; 2）辨别假的内在肾损伤， 治疗期间肌酐升高的患者（目的2）;和3）确定适合出院的患者 并区分其后续不良事件的风险（目标3）。该项目将为 为临床试验奠定基础，以测试肾脏生物标志物指导的ADHF治疗策略。