Mapping the role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors in chronic kidney disease: A scoping review protocol

Abstract

Chronic kidney disease (CKD) is increasingly recognized as a global public health concern, impacting about 800 million people worldwide. Despite having different CKD etiologies, apoptosis, inflammation and fibrosis are the central mechanisms of pathogenesis. Tumor necrosis factor (TNF)- related apoptosis-inducing ligand (TRAIL) is a critical regulator of these mechanisms, suggesting a prominent role in pathogenesis and progression of CKD. Therefore, systematic mapping of the available evidence is pivotal in identifying the exact role of TRAIL and its receptors in CKD. The proposed scoping review will be conducted in line with Arksey and O’Malley’s methodological framework and the Joanna Briggs Institute (JBI) reviewer’s manual. Accordingly, the review will be guided by the five-stage approach, namely (1) identify the research question; (2) identify relevant studies; (3) select studies; (4) chart the data; and (5) collate, summarize, and report the results. Eligibility criteria and search strategies will be formulated based on population, concept, and context (PCC) strategy. Articles published up to January 2026 will be searched using electronic databases (PubMed/ MEDLINE, Science Direct, Scopus, CINAHL, EMBASE, Web of Science and Cochrane Library) and clinical trial registries (ClinicalTrials.gov and WHO ICTRP). Reference lists of relevant reviews retrieved from Google Scholar will also be screened for grey literature. A formal quality appraisal of the selected studies will be conducted using the mixed-method appraisal tool (MMAT version 2018). The reporting will be done following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for the Scoping Reviews checklist. The literature search is expected to commence in March 2026, followed by study selection and data extraction by April 2026. Data synthesis will be completed by June 2026. The review protocol is registered at Open Science Framework (OSF) under https://doi.org/10.17605/OSF.IO/AENBX .