This systematic review and meta-analysis examined circulating syndecan-1 as a biomarker of endothelial glycocalyx injury in sepsis. The authors aimed to quantify the association between syndecan-1 levels and sepsis diagnosis, disease severity, organ complications and clinical prognosis, and to clarify syndecan-1’s complementary value relative to conventional sepsis biomarkers such as lactate, procalcitonin (PCT) and C-reactive protein (CRP).
The study sought to determine whether syndecan-1 could improve multi-domain sepsis risk stratification by reflecting endothelial dysfunction not captured by traditional markers.
The review and meta-analysis were conducted according to PRISMA guidelines. Data synthesis used Review Manager 5.3. Effect sizes were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). The authors predefined subgroup analyses by sepsis definition (Sepsis 1.0/2.0 versus Sepsis 3.0) to assess consistency across diagnostic criteria. Sensitivity analyses excluded studies with serious or critical bias as assessed by ROBINS-I to evaluate robustness.
Main outcome measures included circulating syndecan-1 concentrations in comparisons of sepsis patients versus non-sepsis controls, survivors versus non-survivors, and patients with septic shock, acute kidney injury (AKI), and disseminated intravascular coagulation (DIC).
A total of 29 studies met inclusion criteria, comprising 4,985 participants overall; 3,902 of these participants had sepsis. The pooled dataset therefore represented a broad sample of sepsis patients and relevant control groups as reported in the included studies.
The pooled analysis demonstrated that circulating syndecan-1 concentrations were significantly elevated in sepsis patients compared with non-sepsis controls (SMD = 1.16; 95% CI 0.86 to 1.47; p < 0.00001). Non-survivors had significantly higher syndecan-1 than survivors. Patients with septic shock, AKI, and DIC also exhibited higher syndecan-1 levels, with all reported comparisons reaching p < 0.00001 in the pooled data. These results indicate consistent associations between higher syndecan-1 and both worse outcomes and specific organ complications.
Subgroup analyses stratified by sepsis definitions (Sepsis 1.0/2.0 versus Sepsis 3.0) produced consistent findings, indicating that the association between elevated syndecan-1 and sepsis severity and complications held across diagnostic criteria. Sensitivity analyses that excluded nine studies assessed as having serious or critical ROBINS-I bias confirmed the robustness of the main results; pooled associations remained consistent after excluding higher-bias studies.
The meta-analysis supports the interpretation that elevated circulating syndecan-1 reflects disruption of the endothelial glycocalyx in sepsis. Associations with mortality, septic shock, AKI, and DIC suggest syndecan-1 marks a pathophysiologic domain—endothelial barrier injury and capillary leak—that contributes to organ dysfunction and worse prognosis in sepsis. The authors emphasize that syndecan-1 captures information about endotheliopathy not measured by conventional biochemical markers.
At the same time, the report notes that syndecan-1 lacks specificity for sepsis and therefore is not suited to replace established diagnostic biomarkers.
According to the authors, syndecan-1 may provide incremental prognostic value when used alongside established markers such as lactate, procalcitonin, and C-reactive protein. Its addition could improve multi-domain risk stratification by identifying patients with prominent endothelial injury who may be at higher risk for capillary leak and adverse outcomes related to fluid resuscitation.
The meta-analysis is presented as the most comprehensive quantitative evidence to date supporting integration of “glycocalyx-friendly” management concepts into future sepsis research and guideline development. The findings are intended to inform the design of trials that target endothelial barrier protection and individualized resuscitation strategies.
The abstract reports that syndecan-1 is not specific for sepsis, limiting its diagnostic utility as a standalone marker. The authors conducted bias assessments and sensitivity analyses; exclusion of studies with serious or critical ROBINS-I bias did not materially change pooled results, supporting result robustness. Specific methodological details, study-level characteristics beyond aggregate participant counts, and individual study effect sizes are not presented in the abstract and were therefore not reported here.
In conclusion, elevated circulating syndecan-1 signals endothelial glycocalyx disruption in sepsis and is closely associated with worse prognosis, septic shock and organ dysfunction. It is recommended as a complementary biomarker to conventional sepsis tests for improved risk stratification and as a biomarker domain for trials of endothelial-protective interventions.