Elevated syndecan-1 levels correlate with severity and poor outcomes in patients with sepsisHigher syndecan-1 levels linked to severe sepsis and poor outcomes

AIM: This meta-analysis aimed to assess syndecan-1 as a biomarker reflecting endothelial glycocalyx injury in sepsis, investigate its correlation with disease severity, organ complications and clinical prognosis, and clarifies its complementary value relative to conventional sepsis biomarkers. DESIGN: A systematic review and meta-analysis conducted in accordance with PRISMA guidelines. Data analysis was performed using Review Manager 5.3, with standardized mean differences (SMD) and 95% confidence intervals (CI) calculated. Subgroup analyses were stratified by sepsis definitions (Sepsis 1.0/2.0 vs. 3.0), and sensitivity analyses were performed by excluding studies with serious or critical ROBINS-I bias. PATIENTS: A total of 29 studies involving 4985 participants (3902 with sepsis) were included. MAIN OUTCOME MEASURES: Circulating syndecan-1 levels in sepsis patients versus non-sepsis controls, survivors versus non-survivors, and patients with septic shock, acute kidney injury (AKI) and disseminated intravascular coagulation (DIC). RESULTS: Syndecan-1 levels were significantly higher in sepsis patients than non-sepsis [SMD = 1.16, 95% CI (0.86, 1.47), p < 0.00001]. Non-survivors had significantly elevated levels compared with survivors, and higher levels were also observed in patients with septic shock, AKI and DIC (all p < 0.00001). Subgroup analyses yielded consistent findings across different sepsis definitions, and sensitivity analyses excluding 9 high-bias studies confirmed the robustness of the results. CONCLUSION: Elevated syndecan-1 indicates endothelial glycocalyx disruption in sepsis, and is closely linked to worse prognosis, septic shock and organ dysfunction. As a complementary biomarker to lactate, procalcitonin and C-reactive protein, it improves multi-domain sepsis risk stratification and supports individualized resuscitation and endothelial-protective intervention research. Key messages What is already known on this topic? Syndecan-1 is a marker of endothelial glycocalyx degradation and has been linked to sepsis severity. However, its precise association with prognosis and complications remains unclear, and its clinical value relative to traditional sepsis biomarkers (lactate/PCT/CRP) has not been systematically clarified, necessitating a meta-analysis to quantify its clinical relevance and complementary role. What this study adds This study confirms that syndecan-1 levels are significantly elevated in sepsis, especially in severe cases, non-survivors, and patients with AKI or DIC, validating its role as a specific biomarker of sepsis-associated endothelial glycocalyx injury. Importantly, it clarifies that syndecan-1 is not a replacement for traditional biomarkers but a complementary indicator that captures the endotheliopathy domain unmeasured by lactate/PCT/CRP. Its lack of specificity for sepsis limits its utility as a standalone diagnostic biomarker, but it provides incremental prognostic value for risk stratification. How this study might affect research, practice, or policy Syndecan-1 may serve as a prognostic marker for endothelial dysfunction in sepsis and a stratification tool for identifying patients at high risk of capillary leak and fluid resuscitation-related adverse outcomes. It should be used alongside other biomarkers to inform personalized resuscitation strategies. This meta-analysis provides the most comprehensive quantitative evidence to date for the integration of "glycocalyx-friendly" management into future sepsis research and clinical guidelines, and guides the design of forthcoming trials targeting endothelial barrier protection.