Glomerular Function and Urinary Biomarker Changes between Vancomycin and Vancomycin plus Piperacillin-Tazobactam in a...

Area of Science:

• Pharmacology
• Nephrology
• Toxicology

Background:

• Clinical studies suggest vancomycin (VAN) and piperacillin-tazobactam (TZP) combination may cause additive nephrotoxicity.
• Understanding the specific renal effects of VAN and TZP, individually and in combination, is crucial for patient safety.

Purpose of the Study:

• To evaluate the impact of VAN alone versus VAN + TZP on kidney function and injury in a rat model.
• To compare glomerular filtration rate (GFR) and urinary biomarker changes between treatment groups.

Main Methods:

• Male Sprague-Dawley rats received intravenous VAN, intraperitoneal TZP, or VAN + TZP for 96 hours.
• Real-time GFR was estimated using fluorescein-isothiocyanate sinistrin and a transdermal sensor.
• Urinary biomarkers, including kidney injury molecule-1 (KIM-1), were analyzed.

Main Results:

• Vancomycin (VAN) alone significantly decreased GFR compared to saline controls.
• Rats receiving VAN alone showed significantly higher urinary KIM-1 levels on days 1-4.
• No significant decline in GFR or increase in KIM-1 was observed in the VAN + TZP group compared to VAN alone.

Conclusions:

• Vancomycin (VAN) alone, but not in combination with piperacillin-tazobactam (TZP), led to kidney function decline and injury in this rat model.
• The addition of TZP to VAN did not exacerbate nephrotoxicity.
• These findings suggest that TZP may not worsen VAN-associated kidney injury in this translational model.