Integrated Study of Vancomycin-Induced Nephrotoxicity in the Context of Sepsis

Background: Vancomycin (VAN) is widely used in sepsis but may exacerbate sepsis-associated acute kidney injury (SA-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. Methods: C57BL/6 mice were subjected to lipopolysaccharide (LPS)-induced sepsis, VAN-induced nephrotoxicity, or combined injury. Renal function was continuously assessed using non-invasive percutaneous real-time glomerular filtration rate (GFR) monitoring. Conventional renal injury markers, histopathology, and transcriptomic analyses were performed at 2, 24, and 72 hours. Results: In septic mice, VAN administration caused an early and marked decline in GFR, preceding increases in serum creatinine and blood urea nitrogen. 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 Tnfrsf1a and sustained upregulation of Ccl20 in the combined injury model. Functional enrichment analyses revealed activation of inflammatory and immune-related pathways, including TNF signaling, cytokine–cytokine receptor interaction, and IgSF cell adhesion molecule signaling. Conclusions: Real-time GFR monitoring demonstrates that vancomycin exacerbates SA-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.