Abstract: SA-PO0275
Probenecid and Urinary Acidification Reduce Vancomycin-Associated Nephrotoxicity
Session Information
- AKI: Mechanisms - Cell Signaling
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Le Moulec, Thibault, Sorbonne Universite, Paris, Île-de-France, France
- Luque Rincon, Yosu, Sorbonne Universite, Paris, Île-de-France, France
Group or Team Name
- Corakid Team Paris France
Background
Vancomycin-associated acute kidney injury (AKI) affects up to 20% of treated patients, with no validated preventive or therapeutic strategy. Two mechanisms have been described: direct tubular toxicity and intratubular precipitation of vancomycin–uromodulin casts. Vancomycin undergoes tubular secretion via basolateral OAT and OCT transporters, and its solubility is pH-dependent. We hypothesized that urinary pH modulation and pharmacological inhibition of tubular transporters could reduce vancomycin-associated kidney injury.
Methods
In 8-week-old male C57BL/6J mice, vancomycin (0.5 mg/g IP) was administered on two consecutive days. Urinary pH was modulated by NH4Cl or bicarbonate started 24h before vancomycin. The OAT inhibitor probenecid (0.15 mg/g) or the OCT inhibitor cimetidine (0.1 mg/g) was administered IP 30 min before each vancomycin dose. Probenecid was also tested curatively (after injury onset). Renal outcomes were assessed by plasma urea, transcutaneous GFR, and semi-quantitative histological scoring of acute tubular necrosis (ATN) and cast formation at day 3 and day 8. Intratubular cast dynamics were evaluated by intravital microscopy using a fluorochrome-conjugated vancomycin derivative (Vanco-BODIPY®).
Results
Urinary acidification significantly reduced plasma urea, ATN scores, and cast scores at day 3, whereas alkalinization had no protective effect. Preventive probenecid markedly decreased plasma urea, ATN, and cast formation at day 3, with benefits sustained at day 8 alongside improved GFR. Intravital microscopy confirmed rapid intratubular cast formation within 5 min of vancomycin injection and a marked reduction with probenecid pre-treatment over 45 min. Cimetidine reduced plasma urea but did not improve histological scores. Probenecid had no effect when administered curatively after injury onset.
Conclusion
Urinary acidification reduces vancomycin nephrotoxicity by limiting intratubular cast precipitation, supporting the pathogenic role of this micro-obstructive mechanism. Preventive OAT inhibition by probenecid provides a strong, sustained nephroprotective effect. Given its safety profile, low cost, and wide availability, probenecid is a highly relevant candidate for clinical evaluation in patients at risk of vancomycin-associated AKI.
Acknowledgment
Corakid Team Paris France