CODE-AKI: COnservative Dialysis to Enhance AKI Recovery

CODE-AKI：保守透析促进 AKI 恢复

• 批准号: 10203956
• 负责人: Chi-yuan Hsu
• 金额: $ 51.2万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-11 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10203956
• 关键词: Acute; Acute Renal Failure with Renal Papillary Necrosis; Artificial Kidney; Biological; Blood; Clinical; Clinical Trials; Complication; Cost Savings; Creatinine; Detection; Diagnosis; Dialysis procedure; Excision; Hemodialysis; Hospitals; Hypotension; Injury; Injury to Kidney; Interleukin-18; Interleukin-6; Interleukin-8; Intervention; Intervention Studies; Kidney; LCN2 gene; Liquid substance; Masks; Membrane; Metabolic; Outcome; Output; Participant; Patients; Plasma; Population; Positioning Attribute; Public Health; Randomized; Randomized Controlled Trials; Recovery; Renal Replacement Therapy; Renal function; Schedule; Serum; Specific qualifier value; Supportive care; TNFR-Fc fusion protein; TNFRSF1A gene; Testing; Time; Tubular formation; Urine; Ventilator; Vulnerable Populations; Work; base; clinical practice; hemodynamics; hypoperfusion; immune activation; improved; insight; patient oriented; pilot trial; primary outcome; rat KIM-1 protein; safety and feasibility; safety testing; solute; systemic inflammatory response; trend

ABSTRACT/PROJECT SUMMARY Dialysis-requiring acute kidney injury (AKI-D) is a devastating complication among hospitalized patients for which there are no treatments other than supportive care. Recovery of sufficient renal function to stop dialysis is an unequivocally important clinical and patient-oriented outcome. Shortening dialysis duration and increasing the number of AKI-D patients who recover would have a major clinical, public health and cost-saving impact. However, there is currently no evidence to guide the delivery of dialysis to facilitate recovery. We hypothesize that in patients who have AKI-D and who are hemodynamically stable, a conservative dialysis strategy--in which hemodialysis is not continued unless specific metabolic or clinical indications for RRT are present--will improve the likelihood of renal recovery compared with the current standard clinical practice of thrice-weekly intermittent dialysis. We have conducted a pilot clinical trial to demonstrate the feasibility of this approach. We propose here a 2-center randomized controlled trial to test our conservative dialysis strategy in a larger AKI-D population (N = 220). To shed insight into potential pathophysiological mechanisms, we will examine the impact of the conservative dialysis strategy on not only clinical outcomes but also markers of renal tubular injury and systemic inflammation. Our specific aims are: Aim 1: In hospitalized patients with AKI-D, to test whether a conservative dialysis strategy (compared with a standard thrice-weekly acute dialysis strategy): a. Increases the proportion of patients with renal recovery at hospital discharge--the primary outcome for this trial (defined as being alive and off dialysis at the time of discharge, with sustained independence from dialysis for 14 days which may occur in or out of the hospital); b. Reduces the number of dialysis sessions/week; c. Increases the number of dialysis-free days to study day 28 (days alive and not dependent on dialysis, similar to ventilator-free days). Aim 2: To determine the impact of a conservative dialysis strategy (compared with a standard thrice-weekly acute dialysis strategy) on renal tubular injury and systemic inflammation. Renal tubular injury will be reflected by plasma neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 levels during the first week of the study intervention. Systemic inflammation will be reflected by plasma interleukin [IL]-6, IL-8, IL-18 and soluble tumor necrosis factor receptor-1 levels. In aggregate, the studies proposed here are the next step towards changing the paradigm of dialytic management in patients with prevalent AKI-D and improving clinical outcomes in this vulnerable population.

摘要/项目摘要 透析的急性急性肾脏损伤（AKI-D）是住院患者的毁灭性并发症 除了支持性护理外，没有其他治疗方法。恢复足够的肾功能以阻止透析 是一个非常重要的临床和面向患者的结果。缩短透析持续时间和增加 康复的AKI-D患者人数将产生重大的临床，公共卫生和节省成本的影响。 但是，目前尚无证据指导透析以促进恢复。我们假设 在患有AKI-D并且血液动力学稳定的患者中，一种保守的透析策略 - 除非存在针对RRT的特定代谢或临床指示，否则不会继续哪些血液透析 与当前的三次标准临床实践相比，提高肾脏回收的可能性 间歇性透析。我们进行了一项试验临床试验，以证明这种方法的可行性。我们 在这里提出一项2中心随机对照试验，以在较大的AKI-D中测试我们的保守透析策略 人口（n = 220）。为了深入了解潜在的病理生理机制，我们将研究 保守透析策略的影响不仅对临床结果，而且对肾小管的标志 受伤和全身炎症。我们的具体目的是： 目标1：在患有AKI-D的住院患者中，以测试保守的透析策略（与A相比 标准三次急性透析策略）： 一个。增加医院出院时肾脏恢复患者的比例 - 该试验（被定义为出院时还活着和透析，具有持续的独立性 从透析中可能发生14天，可能发生在医院内或外出）； b。减少/周透析会议的数量； c。增加了学习第28天的无透析天数（活着的天数，不依赖于透析， 类似于无呼吸机的日子）。 目标2：确定保守的透析策略的影响（与每周三次标准相比 急性透析策略）关于肾小管损伤和全身炎症的策略。 血浆中性粒细胞明胶酶相关的脂肪蛋白和肾脏损伤将反映肾小管损伤 研究干预的第一周分子1水平。系统性炎症将由 血浆白介素[IL] -6，IL-8，IL-18和可溶性肿瘤坏死因子受体1水平。总体上， 这里提出的研究是改变患者透明管理范式的下一步 随着AKI-D的流行，并改善了这一脆弱人群的临床结果。