Kidney Injury in Patients with Acute Decompensated Heart Failure

急性失代偿性心力衰竭患者的肾脏损伤

• 批准号: 10448754
• 负责人: Nisha Bansal
• 金额: $ 15.53万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10448754
• 关键词: Acute; Address; Admission activity; Affect; Algorithms; Angiotensinogen; Body Weight Changes; Cardiac; Clinical; Clinical Trials; Complex; Congestive; Creatinine; Critical Illness; Data; EFRAC; Echocardiography; Endothelium; Event; FABP1 gene; Foundations; Functional disorder; Future; Glomerular Filtration Rate; Goals; Guidelines; Health Status; Heart failure; Hospitalization; Hospitals; Inflammation; Injury; Injury to Kidney; Interleukin-18; Investigation; Kidney; Knowledge; LCN2 gene; Length of Stay; Leukocyte L1 Antigen Complex; Literature; Measurement; Measures; Mechanics; Outcome; Oxidative Stress; Patients; Population; Prognosis; Prospective Studies; Public Health; Recurrence; Renal function; Reporting; Risk; Role; Sentinel; Serum; Severities; Standardization; Stress; Symptoms; Testing; Treatment Failure; Treatment Protocols; Tubular formation; Universities; Washington; Withdrawal; Work; acute care; base; evidence base; hemodynamics; high risk; improved; improved outcome; injury and repair; insulin-like growth factor binding protein-related protein 1; ischemic injury; kidney repair; novel; preservation; prognostic; public health priorities; recruit; response; treatment strategy

ABSTRACT Hospitalization for acute decompensated heart failure (ADHF) is a significant public health issue and represents a sentinel prognostic event, with high risk of poor clinical outcomes during and after the hospitalization. Investigation to improve the care of ADHF patients is a public health priority. The kidneys have a central role in the acute management and prognosis of ADHF. Kidney injury is highly prevalent in ADHF and is the culmination of hemodynamic alterations, neurohormonal dysregulation, and oxidative stress which cause intra-kidney endothelial damage, inflammation and ischemic injury. Kidney injury is also a key component in decisions of initiation and withdrawal of standard AHDF therapies, which ultimately affects clinical prognosis of ADHF. However, systematic measurement and consideration of kidney injury is not incorporated into algorithms of ADHF therapies, likely due to limitations of current clinically available kidney injury measures. Serum creatinine has traditionally been used to define kidney injury in ADHF, however rises late and is slow to change in response to ongoing kidney injury or repair; which limits its use in dynamic conditions such as ADHF. Studies have shown that serum creatinine is not associated with systemic decongestion or with short-term prognosis in ADHF. Thus, current ADHF guidelines do not endorse serial measures of serum creatinine. The goal of this proposal is to identify novel kidney injury markers that can guide therapy and better determine prognosis in ADHF; thereby improve in-hospital and long-term outcomes. To address this knowledge gap, we propose to conduct a large, prospective study of ADHF patients to determine: (1) if systematic, serial measurements of novel kidney injury markers change in response to a standardized, evidence-based ADHF treatment protocol; (2) and whether these changes are associated with patient-reported, in-hospital and long-term outcomes. Based on previous literature, we have chosen to study a panel of novel kidney injury measures of endothelial injury, inflammation, tubular stress/damage which may better reflect intra-kidney pathophysiology, and may be more dynamic to reflect kidney injury/repair compared with serum creatinine. These novel kidney injury measures are poised to be clinically available in the near future, however are not well studied in ADHF. To support our hypothesis, we conducted a pilot prospective study of 62 patients admitted with ADHF and found that novel kidney injury measures demonstrated greater relative change in response to standardized ADHF therapies and correlated well with systemic congestion; while serum creatinine was relatively static and correlated poorly with systemic congestion. This promising pilot data supports the scientific rationale and feasibility of the proposed work. The data from this study will be used to identify the most promising kidney injury markers in ADHF patients and may be the foundation of future mechanistic studies or a clinical trial to test an ADHF treatment strategy guided by novel kidney injury markers.

抽象的 急性失代偿性心力衰竭（ADHF）住院治疗是一个重大的公共卫生问题， 代表一个哨兵预后事件，在治疗期间和之后出现不良临床结果的风险很高 住院治疗。改善 ADHF 患者护理的调查是公共卫生的首要任务。肾脏 在 ADHF 的急性治疗和预后中发挥着核心作用。肾损伤在以下地区非常普遍 ADHF 是血流动力学改变、神经激素失调和氧化应激的最终结果 导致肾内内皮损伤、炎症和缺血性损伤。肾损伤也是关键 标准 AHDF 治疗的启动和退出决策的组成部分，最终影响 ADHF 的临床预后。然而，对肾损伤的系统测量和考虑并不适用。 纳入 ADHF 治疗算法中，可能是由于当前临床可用肾脏的限制 伤害措施。血清肌酐传统上被用来定义 ADHF 的肾损伤，但其升高 对持续的肾脏损伤或修复做出反应较晚且变化缓慢；这限制了它在动态中的使用 ADHF 等疾病。研究表明，血清肌酐与全身性疾病无关。 ADHF 的缓解或短期预后。因此，当前的 ADHF 指南不支持串行 血清肌酐的测量。该提案的目标是确定新的肾损伤标记物，这些标记物可以 指导 ADHF 的治疗并更好地确定预后；从而改善院内和长期结果。 为了弥补这一知识差距，我们建议对 ADHF 患者进行一项大型前瞻性研究，以 确定：（1）新型肾损伤标志物的系统性、系列测量是否会因某种原因而发生变化 标准化、循证的 ADHF 治疗方案； (2) 以及这些变化是否与 患者报告的、院内的和长期的结果。根据以往的文献，我们选择研究 一组新的肾损伤测量指标，包括内皮损伤、炎症、肾小管应激/损伤，这可能 更好地反映肾内病理生理学，并且可能更动态地反映肾损伤/修复 与血清肌酐。这些新颖的肾损伤措施有望在不久的将来应用于临床 然而，ADHF 的未来尚未得到充分研究。为了支持我们的假设，我们进行了试点前瞻性 对 62 名 ADHF 患者进行的研究发现，新的肾损伤措施显示出更大的肾损伤 对标准化 ADHF 治疗的反应相对变化，与全身充血密切相关； 而血清肌酐相对稳定，与全身充血相关性较差。这 有前景的试点数据支持了拟议工作的科学原理和可行性。数据 这项研究将用于确定 ADHF 患者中最有希望的肾损伤标志物，并且可能 为未来的机制研究或测试 ADHF 治疗策略的临床试验奠定基础 新型肾损伤标志物。