Integrated Study of Vancomycin-Induced Nephrotoxicity in the Context of Sepsis: Animal Models and Transcriptomics

Vancomycin exacerbates kidney injury in a mouse model of LPS-induced sepsis. GFR is a more sensitive and earlier indicator of vancomycin-associated kidney injury than serum creatinine or BUN.

Vancomycin (VAN) is widely used in sepsis but may exacerbate sepsis-associated AKI. The mechanisms by which VAN aggravates renal injury in the septic context remain unclear, and early functional changes are difficult to detect using conventional biomarkers.

C57BL/6 mice were subjected to LPS-induced sepsis, VAN-induced nephrotoxicity, or combined injury. Renal function was continuously assessed using noninvasive percutaneous real-time GFR monitoring. Conventional renal injury markers, histopathology, and transcriptomic analyses were performed at 2, 24, and 72 hours.

In septic mice, VAN administration caused an early and marked decline in GFR, preceding increases in serum creatinine and BUN. Compared with sepsis alone, combined LPS and VAN treatment resulted in more sustained renal dysfunction and more severe tubular injury. Transcriptomic profiling identified early and persistent upregulation of TNF receptor superfamily, member 1a and sustained upregulation of C-C motif chemokine ligand 20 in the combined injury model. Functional enrichment analyses revealed activation of inflammatory and immune-related pathways, including TNF signaling, cytokine-cytokine receptor interaction, and immunoglobulin superfamily cell adhesion molecule signaling.

Real-time GFR monitoring demonstrates that VAN exacerbates sepsis-associated AKI by inducing early functional impairment. Transcriptomic changes suggest that enhanced inflammatory signaling and immune cell recruitment contribute to VAN-aggravated renal injury in sepsis.