Abstract: TH-PO044
Urinary Acidification and Pharmacological Inhibition of OCT/OAT Reduce the Severity of Experimental Vancomycin-Induced AKI
Session Information
- AKI: Epidemiology, Risk Factors, and Prevention - 1
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 101 AKI: Epidemiology, Risk Factors, and Prevention
Authors
- Luque, Yosu, Sorbonne Universite, Paris, Île-de-France, France
- Le Moulec, Thibault, Sorbonne Universite, Paris, Île-de-France, France
- Rozenblat, David, Assistance Publique - Hopitaux de Paris, Paris, Île-de-France, France
- Louedec, Liliane, Sorbonne Universite, Paris, Île-de-France, France
- Hadchouel, Juliette, INSERM, Paris, Île-de-France, France
- Girault, Gaëtan, INSERM, Paris, Île-de-France, France
- Marquié, Marine, INSERM, Paris, Île-de-France, France
- Mesnard, Laurent, Sorbonne Universite, Paris, Île-de-France, France
- Sandrine, Placier, INSERM, Paris, Île-de-France, France
Background
Vancomycin, a glycopeptide antibiotic, is used clinically but causes nephrotoxicity in 5-43% of cases via direct tubular damage and vancomycin-uromodulin casts. While vancomycin's solubility increases in acidic media, uromodulin's decreases, complicating the prediction of urinary pH modulation effects. Vancomycin is excreted through glomerular filtration and proximal tubular secretion via organic cation (OCT) and anion (OAT) transport systems. This study investigates the effects of urinary pH modulation and OCT/OAT blockade with cimetidine and probenecid on vancomycin-induced renal lesions in a murine model.
Methods
Eight-week-old male C57BL/6J mice received an intraperitoneal injection of vancomycin at a dose of 0.5 mg/g once daily for two consecutive days, followed by euthanasia and tissue collection on the third day. Urinary alkalinization was induced by providing 0.2 M sodium bicarbonate in drinking water, while acidification was achieved by incorporating 2% ammonium chloride (NH4Cl) into their food. Cimetidine (100 mg/kg) and probenecid (150 mg/kg) were administered intraperitoneally 30 minutes before each vancomycin injection.
Results
Urinary acidification reduced vancomycin-induced renal failure, as evidenced by lower creatinine levels (31.88 ± 16.89 vs. 46.39 ± 15.47 µmol/L, p = 0.0212) and plasma urea levels (29.48 ± 15.48 vs. 46.19 ± 13.31 mmol/L, p = 0.0013). Urinary alkalinization had no effect in kidney injury. Probenecid also reduced vancomycin-induced kidney injury, as indicated by serum creatinine (16.20 ± 3.088 vs. 46.39 ± 15.47 µmol/L, p < 0.0001) and plasma urea levels (22.65 ± 12.96 vs. 47.99 ± 16.85 mmol/L, p < 0.001). Additionally, there was a significant decrease in tubular lesions and the number of casts. Cimetidine showed significant improvement in creatinine levels only (28.67 ± 10.40 vs. 46.39 ± 15.47 µmol/L, p = 0.0116).
Conclusion
Urinary acidification, but not alkalinization, prevents vancomycin-induced renal failure and kidney damage. These results suggest that uromodulin is not necessary for vancomycin cast formation. Additionally, administering probenecid before vancomycin injections also prevents renal failure and kidney damage, suggesting potential therapy options for these patients.
Funding
- Government Support – Non-U.S.