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急性肾损伤新型疗法实施的障碍与机遇:一篇叙述性综述

Roadblocks and Opportunities to the Implementation of Novel Therapies for Acute Kidney Injury: A Narrative Review.

作者信息

Misra Paraish S, Silva E Silva Vanessa, Collister David

机构信息

Kidney Research Scientist Core Education and National Training Program, Canada.

McEwen Stem Cell Institute, Department of Medicine, University of Toronto, ON, Canada.

出版信息

Can J Kidney Health Dis. 2019 Oct 9;6:2054358119880519. doi: 10.1177/2054358119880519. eCollection 2019.

Abstract

BACKGROUND

Acute kidney injury (AKI) is a complex and heterogeneous clinical syndrome with limited effective treatment options. Therefore, a coherent research structure considering AKI pathophysiology, treatment, translation, and implementation is critical to advancing patient care in this area.

PURPOSE OF REVIEW

In this narrative review, we discuss novel therapies for AKI from their journey from bench to bedside to population and focus on roadblocks and opportunities to their successful implementation.

SOURCES OF INFORMATION

Peer-reviewed articles, opinion pieces from research leaders and research funding agencies, and clinical and research expertise.

METHODS

This narrative review details the challenges of translation of preclinical studies in AKI and highlights trending research areas and innovative designs in the field. Key developments in preclinical research, clinical trials, and knowledge translation are discussed. Furthermore, this article discusses the current need to involve patients in clinical research and the barriers and opportunities for effective knowledge translation.

KEY FINDINGS

Preclinical studies have largely been unsuccessful in generating novel therapies for AKI, due both to the complexity and heterogeneity of the disease, as well as the limitations of commonly available preclinical models of AKI. The emergence of kidney organoid technology may be an opportunity to reverse this trend. However, the roadblocks encountered at the bench have not precluded researchers from running well-designed and impactful clinical trials, and the field of renal replacement therapy in AKI is highlighted as an area that has been particularly active. Meanwhile, knowledge translation initiatives are bolstered by the presence of large administrative databases to permit ongoing monitoring of clinical practices and outcomes, with research output from such evaluations having the potential to directly impact patient care and inform the generation of meaningful clinical practice guidelines.

LIMITATIONS

There are limited objective data examining the process of knowledge creation and translation in AKI, and as such the opinions and research areas of the authors are significantly drawn upon in the discussion.

IMPLICATIONS

The use of an organized knowledge-to-action framework involving multiple stakeholders, especially patient partners, is critical to translating basic research findings to improvements in patient care in AKI, an area where effective treatment options are lacking.

摘要

背景

急性肾损伤(AKI)是一种复杂且异质性的临床综合征,有效治疗选择有限。因此,构建一个涵盖AKI病理生理学、治疗、转化及实施的连贯研究架构,对于推动该领域的患者护理进展至关重要。

综述目的

在本叙述性综述中,我们探讨AKI的新型疗法,从其从实验室到临床再到人群应用的历程,并聚焦于其成功实施过程中的障碍与机遇。

信息来源

同行评审文章、研究领域领导者和研究资助机构的观点文章,以及临床和研究专业知识。

方法

本叙述性综述详细阐述了AKI临床前研究转化过程中的挑战,并突出了该领域的研究趋势和创新设计。讨论了临床前研究、临床试验及知识转化方面的关键进展。此外,本文还讨论了当前让患者参与临床研究的必要性,以及有效知识转化的障碍与机遇。

主要发现

由于疾病的复杂性和异质性,以及常用AKI临床前模型的局限性,临床前研究在开发AKI新型疗法方面大多未取得成功。肾脏类器官技术的出现可能是扭转这一趋势的契机。然而,实验室中遇到的障碍并未阻止研究人员开展精心设计且有影响力的临床试验,AKI的肾脏替代治疗领域被视为特别活跃的领域。与此同时,大型管理数据库的存在为知识转化计划提供了支持,从而能够持续监测临床实践和结果,此类评估的研究成果有可能直接影响患者护理,并为制定有意义的临床实践指南提供依据。

局限性

关于AKI知识创造和转化过程的客观数据有限,因此在讨论中大量借鉴了作者的观点和研究领域。

启示

使用一个由多个利益相关者(尤其是患者伙伴)参与的有组织的知识到行动框架,对于将基础研究成果转化为改善AKI患者护理至关重要,因为该领域缺乏有效的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1898/6787878/186f3b702086/10.1177_2054358119880519-fig1.jpg

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