Two therapeutic approaches for vancomycin-induced acute kidney injury: urinary acidification or inhibition of organic anion transporters with probenecid

Vancomycin-induced nephrotoxicity, associated with direct tubular damage and the formation of vancomycin-uromodulin casts, has no effective treatment strategies. This research on C57Bl/6J mice evaluates the impact of urinary pH modulation and the inhibition of the organic anion transporters (OAT) with probenecid on vancomycin-related kidney injury. Prior to vancomycin administration, urinary pH was adjusted by bicarbonate alkalinization or ammonium chloride acidification. Probenecid was given before each vancomycin dose. Renal function assessment, histological analyses, and intravital microscopy were performed. Urinary acidification decreased plasma urea and improved histological scores of acute tubular necrosis (ATN) and cast formation on the third day. Similarly, probenecid treatment reduced plasma urea and ameliorated tubular lesions, with a significant reduction in cast formation beginning on the third day as confirmed by intravital microscopy. Long-term, probenecid consistently improved kidney function and histological scores with less ATN and cast formation by day 8 and reduced fibrosis by day 30. Modifying urinary pH and inhibiting OAT with probenecid significantly reduces vancomycin-induced kidney injury, offering viable preventive strategies to mitigate nephrotoxicity in clinical settings.