Glycocalyx and Endothelial Biomarkers as Prognostic Indicators in Sepsis: A Systematic Review and Meta-Analysis

Abstract

Sepsis-induced endothelial dysfunction, marked by degradation of the endothelial glycocalyx and activation of endothelial cells, plays a pivotal role in the progression to organ failure and mortality. Biomarkers reflecting glycocalyx damage have demonstrated prognostic potential; however, their associations with clinical outcomes remain variable. We systematically evaluated the prognostic utility of glycocalyx-associated biomarkers (syndecan-1, heparan sulfate, hyaluronate) and the endothelial activation marker endocan in sepsis with respect to mortality, organ dysfunction, and inter-study heterogeneity. We included 23 studies through May 2025 encompassing 4529 patients with sepsis. Two independent reviewers extracted data using standardized protocols, including biomarker concentrations and clinical outcomes such as mortality, multiple organ dysfunction syndrome, and respiratory failure. Risk of bias was assessed using the NOS, with 75% of studies rated as low risk. Elevated syndecan-1 was significantly associated with increased mortality (nine studies, n = 2167; OR 2.04, 95% CI, 1.66–2.51; p < 0.05; I² = 84%). Similarly, elevated endocan predicted mortality with a stronger effect size (six studies, n = 435; OR 5.06, 95% CI, 2.52–10.18; p < 0.05) and low heterogeneity. In contrast, syndecan-1 levels were not significantly associated with multiple organ dysfunction syndrome (OR 2.35, 95% CI, 0.93–5.94; I² = 94%) or respiratory failure (OR 1.05, 95% CI, 0.27–4.02; I² = 91%). The majority of studies were ICU-based (78.3%), primarily adult cohorts (91.3%), with syndecan-1 the most commonly assessed biomarker (65.2%). Syndecan-1 and endocan serve as prognostic biomarkers for mortality in sepsis, with endocan demonstrating greater inter-study consistency.