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

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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Abstract

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. 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. Ethical approval is not required. Findings will be published in a peer-reviewed journal and presented at scientific meetings. CRD42021265550.
Original languageEnglish
Article numbere100240
Pages (from-to)1-16
Number of pages16
JournalBMJ Open Science
Volume5
Issue number1
Early online date15 Nov 2021
DOIs
Publication statusE-pub ahead of print - 15 Nov 2021

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