Abstract: TH-PO0121
In Vitro Nephrotoxicity of Combined Piperacillin and Vancomycin
Session Information
- AKI: Mechanisms - 1
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Evans, Rachel C., Vanderbilt University Medical Center, Nashville, Tennessee, United States
- Roy, Shuvo, University of California San Francisco, San Francisco, California, United States
- Fissell, William Henry, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Group or Team Name
- The Kidney Project.
Background
Piperacillin-tazobactam and vancomycin are widely used parenteral antibiotics. Concern that concomitant use of piperacillin and vancomycin is nephrotoxic has led some institutions to choose different empiric antibiotic combinations for sepsis, but the toxicity is controversial. Using culture conditions with improved organic anion transporter expression, we examined the nephrotoxicity of these antibiotics by supplementing culture media with piperacillin and vancomycin
Methods
Primary human renal proximal tubule cells (Lonza, Basel) were seeded at 10^5 cells per cm^2 on permeable supports and grown in 50:50 DMEM/F12 with ITS, hydrocortisone, T3, and ascorbic acid in humidified 5% CO2/Air. 24 hours after seeding the cell culture plates were placed on an orbital shaker to generate 1 dyne/cm2 average fluid shear stress. 1 week after confluence, media was supplemented with metformin and SB431542. Media was changed every 48-72 hours. Piperacillin at 100, 200, and 400 micrograms/ml in combination with vancomycin at 20, 40, and 80 micrograms per/ml (“PV”) was added to apical and basal media sequentially for 48 hours with a twelve-day washout period between. Apicobasal leak was assessed using TRITC-labelled dextrans, and apicobasal transport was measured by media mass change.
Results
PV had no effect on leak or transport at 100/20, but leak increased and transport decreased at 200/40 and 400/80 concentrations. Cells that were not treated with metformin and SB431542 did not show statistically significant differences in leak or transport at any PV dose. After withdrawal of PV, cells returned to their baseline level of function in two weeks.
Conclusion
Media supplementation with combined piperacillin and vancomycin causes injury in cultured renal tubule cells. Enhanced culture conditions with ALK5 inhibition and metformin appear necessary to observe the effect, possibly due to upregulation of organic anion transporters. The concentration of vancomycin in media to cause injury is similar to concentrations that would be expected to cause nephrotoxicity in vivo. More research is needed to determine whether synergistic toxicity is present and if so whether specific prophylaxis will reduce toxicity.
Funding
- Private Foundation Support