Abstract: TH-PO0120
Two Therapeutic Approaches for Vancomycin-Associated AKI: Urinary Acidification or Inhibition of Organic Anion Transporters with Probenecid
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
- Luque, Yosu, Sorbonne Universite, Paris, Île-de-France, France
- Le Moulec, Thibault, INSERM UMR_1155, Paris, Ile de France, France
- Raimundo, Joyce Regina Santos, INSERM UMR_1155, Paris, Ile de France, France
- Rozenblat, David, INSERM UMR_1155, Paris, Ile de France, France
- Frère, Perrine, INSERM UMR_1155, Paris, Ile de France, France
- Samson, Chloé, INSERM UMR_1155, Paris, Ile de France, France
- Louedec, Liliane, INSERM UMR_1155, Paris, Ile de France, France
- Girault, Gaëtan, INSERM UMR_1155, Paris, Ile de France, France
- Marquié, Marine, INSERM UMR_1155, Paris, Ile de France, France
- Rafat, Cedric, Hopital Tenon, Paris, Île-de-France, France
- Letavernier, Emmanuel, Sorbonne Universite, Paris, Île-de-France, France
- Mesnard, Laurent, Sorbonne Universite, Paris, Île-de-France, France
- Hadchouel, Juliette, INSERM UMR_1155, Paris, Ile de France, France
- Sandrine, Placier, INSERM UMR_1155, Paris, Ile de France, France
Group or Team Name
- Corakid.
Background
Vancomycin, a glycopeptide antibiotic, is widely used in clinical settings but can cause nephrotoxicity through direct tubular damage and vancomycin–uromodulin cast formation. To date, effective therapeutic strategies are lacking. Given that vancomycin’s solubility is pH-dependent, the impact of urinary pH modulation remains poorly understood. Furthermore, vancomycin is eliminated via glomerular filtration and proximal tubular secretion, particularly through the organic anion transporter (OAT) system. This study investigates the effects of urinary pH modulation and OAT inhibition with probenecid on vancomycin-associated kidney injury in a murine model.
Methods
Eight-week-old male C57Bl/6J mice received vancomycin (0.5 mg/g/day, intraperitoneally for 2 days) to induce AKI. Urinary pH was modulated 24 hours before treatment using 0.2 M sodium bicarbonate in drinking water (alkalinization) or 2% ammonium chloride in food (acidification). Probenecid (0.15 mg/g, intraperitoneally) was administered 30 minutes prior to each vancomycin injection. Mice were euthanized, and tissues collected on day 3. In a separate cohort, the effects of probenecid were evaluated on day 8. Endpoints included plasma urea levels, kidney histology, and intravital microscopy.
Results
At day 3, urinary acidification significantly lowered plasma urea (29.5 ± 15.5 vs. 46.2 ± 13.3 mmol/L, p=0.001), reduced tubular injury (p=0.005), and decreased cast formation (p=0.032). Probenecid provided stronger protection, with plasma urea reduced to 16.1 ± 4.0 vs. 46.2 ± 13.3 mmol/L (p<0.0001), fewer tubular lesions (p=0.031), and fewer casts (p=0.027). Intravital microscopy confirmed a marked reduction in cast formation (p=0.0002). At day 8, probenecid-treated mice maintained better renal function (15.5 ± 4.0 vs. 29.5 ± 15.5 mmol/L, p=0.0003), along with sustained reductions in tubular lesions (p=0.044) and cast scores (p=0.047).
Conclusion
This study demonstrates that urinary acidification and inhibition of OAT via probenecid significantly reduce vancomycin-associated AKI. These findings suggest promising preventive strategies to mitigate nephrotoxicity in clinical practice.
Funding
- Government Support – Non-U.S.