Protocol for a preclinical systematic review and meta-analysis of pharmacological targeting of peroxisome proliferator-activated receptors in experimental renal injury.

Q1 Medicine
BMJ Open Science Pub Date : 2021-11-15 eCollection Date: 2021-01-01 DOI:10.1136/bmjos-2021-100240
William P Martin, Yeong H D Chuah, Emer Conroy, Alison L Reynolds, Conor Judge, Francisco J López-Hernández, Carel W le Roux, Neil G Docherty
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引用次数: 0

Abstract

Introduction: Impaired lipid metabolism in the renal tubule plays a prominent role in the progression of renal fibrosis following acute kidney injury (AKI) and in chronic kidney disease (CKD). Peroxisome proliferator-activated receptors (PPARs) are promising druggable targets to mitigate renal fibrosis by redirecting metabolism, including restoration of fatty acid oxidation (FAO) capacity. We aim to synthesise evidence from preclinical studies of pharmacological PPAR targeting in experimental renal injury, and inform the design of future studies evaluating PPAR-mediated restoration of FAO in AKI and CKD.

Methods and analysis: Studies reporting on the impact of pharmacological PPAR modulation in animal models of renal injury will be collected from MEDLINE (Ovid), Embase and Web of Science databases. Predefined eligibility criteria will exclude studies testing medications which are not specific ligands of one or more PPARs and studies involving multimodal pharmacological treatment. The Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool and Collaborative Approach to Meta-Analysis and Review of Animal Experimental Studies checklist will be used to assess quality of the included studies. Data extraction will be followed by a narrative synthesis of the data and meta-analysis where feasible. Analysis will be performed separately for AKI, CKD and renal transplant models. Subgroup analyses will be performed based on study design characteristics, PPAR isotype(s) targeted, and classes of PPAR-targeting medications used. Risk of publication bias will be assessed using funnel plotting, Egger's regression and trim-and-fill analysis.

Ethics and dissemination: Ethical approval is not required. Findings will be published in a peer-reviewed journal and presented at scientific meetings.

Prospero registration number: CRD42021265550.

Abstract Image

在实验性肾损伤中以过氧化物酶体增殖激活受体为药理靶点的临床前系统综述和荟萃分析方案。
导言:肾小管脂质代谢受损在急性肾损伤(AKI)和慢性肾病(CKD)的肾纤维化进程中起着重要作用。过氧化物酶体增殖激活受体(PPARs)是很有希望的药物靶点,可通过调整新陈代谢(包括恢复脂肪酸氧化(FAO)能力)来减轻肾脏纤维化。我们旨在综合实验性肾损伤中 PPAR 药理靶点临床前研究的证据,为今后评估 PPAR 介导的恢复 AKI 和 CKD 中 FAO 的研究设计提供参考:将从 MEDLINE (Ovid)、Embase 和 Web of Science 数据库中收集有关药理 PPAR 调节对肾损伤动物模型影响的研究报告。预定义的资格标准将排除测试非一种或多种PPARs特异配体药物的研究以及涉及多模式药物治疗的研究。将使用实验动物实验系统性审查中心的偏倚风险工具和动物实验研究元分析和审查协作方法清单来评估纳入研究的质量。提取数据后,将对数据进行叙述性综合,并在可行的情况下进行荟萃分析。分析将针对 AKI、CKD 和肾移植模型分别进行。将根据研究设计特点、所针对的 PPAR 同工型和所使用的 PPAR 靶向药物类别进行亚组分析。将使用漏斗图法、Egger回归法和修剪填充分析法对发表偏倚风险进行评估:无需伦理批准。研究结果将在同行评议期刊上发表,并在科学会议上展示:CRD42021265550。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMJ Open Science
BMJ Open Science Medicine-General Medicine
CiteScore
10.00
自引率
0.00%
发文量
9
审稿时长
31 weeks
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