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Soluble urokinase plasminogen activator receptor (suPAR) as a prognostic marker of mortality in healthy, general, and patient populations: protocol for a systematic review and meta-analysis

Research output: Contribution to journalArticle

Original languageEnglish
JournalBMJ Open
Publication statusAccepted/In press - 25 May 2020

Bibliographical note

first author Jens Vang Petersen, but is not a KCL staff

King's Authors

Abstract

Introduction: Chronic inflammation is increasingly recognized as a major contributor to disease, disability, and ultimately death, but measuring the levels of chronic inflammation remains non-canonized, making it difficult to relate chronic inflammation and mortality. Soluble urokinase plasminogen activator receptor (suPAR), an emerging biomarker of chronic inflammation, has been proposed as a prognostic biomarker associated with future incidence of chronic disease and mortality in general as well as patient populations. Proper prognostic biomarkers are important as they can help improve risk stratification in clinical settings and provide guidance in treatment or lifestyle decisions as well as in the design of randomized trials. Here, we wish to summarize the evidence about the overall association of the biomarker suPAR with mortality in healthy, general, and patient populations across diseases.
Methods and analysis: The search will be conducted using Medline, Embase, and Scopus databases from their inception through 28 February 2020 to identify studies investigating “suPAR” and “mortality”. Observational studies and control groups from intervention studies written in English or Danish will be included. The “Quality In Prognosis Studies” tool will be used to assess the risk of bias for the studies included. Unadjusted and adjusted mortality outcome measures (e.g., risk ratios, odds ratios, hazard ratios) with 95% CIs will be extracted for healthy individuals, general and patient populations. The primary outcome is all-cause mortality within any given follow-up. Subgroup analyses will be performed based on time of outcome, cause of death, population type, adjustments for conventional risk factors and inflammation markers, etc.
Ethics and dissemination: This systematic review will synthesize evidence on the use of suPAR as a prognostic marker for mortality. The results will be disseminated by publication in a peer-reviewed journal. Data used will be obtained from published studies, and ethics approval is therefore not necessary for this systematic review.
STRENGTHS AND LIMITATIONS OF THIS STUDY
- To the best of our knowledge, this is the first systematic review and meta-analysis that investigates the association between suPAR and mortality across general and patient populations.
- This review will provide valuable new knowledge for researchers studying chronic inflammation’s effect on both short- and long-term health, and for clinicians using suPAR in clinical settings to stratify patients.
- Study selection, data extraction, and quality assessment will be performed independently by two reviewers.
- The results will be discussed in context with other studies in the field.
- Common to most meta-analyses, significant heterogeneity may exist, which will be investigated thoroughly with subgroup analyses and meta-regressions.  

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