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/项目总结 需要透析的急性肾损伤（AKI-D）是住院患者中的一种毁灭性并发症， 除了支持性治疗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， AKI-D患者的康复人数将对临床、公共卫生和成本节约产生重大影响。 然而，目前没有证据可以指导透析的输送以促进恢复。我们假设 在患有AKI-D且血流动力学稳定的患者中， 除非存在RRT的特定代谢或临床指征，否则不继续进行血液透析， 与目前每周三次的标准临床实践相比， 间歇性透析我们已经进行了一项试点临床试验，以证明这种方法的可行性。我们 我在此提出了一项双中心随机对照试验，以测试我们在较大AKI-D患者中的保守透析策略 人群（N = 220）。为了深入了解潜在的病理生理机制，我们将研究 保守透析策略不仅对临床结局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： 目的1：在AKI-D住院患者中，测试保守透析策略（与 标准每周三次急性透析策略）： a.增加出院时肾功能恢复的患者比例---这是 本试验（定义为出院时存活且未接受透析，具有持续的独立性 透析14天，可能发生在医院内外）; B.减少每周透析次数; C.增加至研究第28天的无透析天数（存活且不依赖透析的天数， 类似于无呼吸机的天数）。 目的2：确定保守透析策略（与标准每周三次透析策略相比）的影响 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 分子-1水平在研究干预的第一周。全身性炎症将通过以下方式反映： 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。总体而言， 这里提出的研究是改变患者透析管理模式的下一步 AKI-D的流行和改善这一脆弱人群的临床结局。