CODE-AKI: COnservative Dialysis to Enhance AKI Recovery

CODE-AKI：保守透析促进 AKI 恢复

• 批准号: 10912233
• 负责人: Chi-yuan Hsu
• 金额: $ 12.81万
• 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 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10912233
• 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; Hospitalization; Hospitals; Hypotension; IL18 gene; Injury; Injury to Kidney; Interleukin-6; Interleukin-8; Intervention; Intervention Studies; Kidney; LCN2 gene; Liquid substance; Masks; Membrane; Metabolic; Outcome; Output; Participant; Patient-Focused Outcomes; 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; clinical practice; hemodynamics; hypoperfusion; immune activation; improved; insight; 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 需要透析的急性肾损伤（AKI-D）是住院患者的一种毁灭性并发症 除了支持性护理之外没有其他治疗方法。恢复足够的肾功能以停止透析 是一个明确重要的临床和以患者为导向的结果。缩短透析时间并增加 AKI-D 患者康复的数量将对临床、公共卫生和节省成本产生重大影响。 然而，目前没有证据可以指导进行透析以促进康复。我们假设 对于 AKI-D 且血流动力学稳定的患者，保守的透析策略 除非存在 RRT 的特定代谢或临床指征，否则不会继续进行血液透析 - 将 与目前每周三次的标准临床实践相比，提高肾脏恢复的可能性 间歇性透析。我们进行了一项试点临床试验来证明这种方法的可行性。我们 在此提出一项 2 中心随机对照试验，以在更大的 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，我们将检查 保守透析策略不仅对临床结果而且对肾小管标志物的影响 损伤和全身炎症。我们的具体目标是： 目标 1：在患有 AKI-D 的住院患者中，测试保守透析策略是否可行（与传统透析策略相比） 标准每周三次急性透析策略）： 一个。提高出院时肾脏恢复的患者比例——这是治疗的主要结局 该试验（定义为出院时还活着且未进行透析，并且具有持续的独立性） 14 天的透析（可能在医院内或医院外进行）； b.减少每周透析次数； c.将无透析天数增加到研究第 28 天（存活且不依赖透析的天数， 类似于没有呼吸机的日子）。 目标 2：确定保守透析策略的影响（与标准每周三次透析策略相比） 急性透析策略）对肾小管损伤和全身炎症的影响。 肾小管损伤将通过血浆中性粒细胞明胶酶相关脂质运载蛋白和肾损伤来反映 研究干预第一周期间的分子 1 水平。全身炎症反应会反映在 血浆白细胞介素 [IL]-6、IL-8、IL-18 和可溶性肿瘤坏死因子受体-1 水平。总的来说， 这里提出的研究是改变患者透析管理模式的下一步 与普遍的 AKI-D 相关并改善这一弱势群体的临床结果。