Biomarkers of Microcirculatory Dysfunction in Sepsis: A Pilot Prospective Observational Study

Area of Science:

• Biomarker discovery
• Sepsis research
• Microvascular dysfunction

Background:

• Sepsis is associated with microvascular dysfunction and endothelial glycocalyx (eGC) degradation.
• Urinary glycosaminoglycans (GAGs) are potential biomarkers for eGC degradation.

Purpose of the Study:

• To compare sublingual microscopy (SLM) with urinary GAG assays (DMMB, LC-MS/MS) for detecting microvascular dysfunction in sepsis.
• To evaluate GAGs as biomarkers in sepsis and septic shock.

Main Methods:

• Prospective, observational case-control study at Denver Health Medical Center.
• Included 44 sepsis/septic shock patients and 24 healthy controls.
• Measured SLM parameters and urinary GAGs (DMMB, LC-MS/MS for HS, DS, KS).

Main Results:

• LC-MS/MS quantification of HS showed higher diagnostic performance (AUC 0.85) for sepsis than SLM (AUC 0.71) and DMMB GAGs (AUC 0.62).
• LC-MS/MS HS levels strongly correlated with HILIC-MS validation (R² = 0.97).
• DMMB GAGs associated with HS subtypes and SLM density.

Conclusions:

• LC-MS/MS quantification of HS is the most discriminative biomarker for sepsis among the evaluated methods.
• SLM has moderate utility but faces bedside application challenges.
• Concordance across methods supports eGC degradation in sepsis pathophysiology, highlighting LC-MS/MS potential for clinical use.