Reduction of vancomycin-associated acute kidney injury with montelukast

Vancomycin ranks amongst the most utilized antimicrobial agents in the treatment of serious β-lactam-resistant Gram-positive infections, but its use has been associated with nephrotoxicity. Reduction of acute kidney injury (AKI) has been reported in pre-clinical models with adjuvant montelukast. The purpose of the study was to ascertain if montelukast was associated with a reduction in the prevalence of vancomycin-associated AKI. In this retrospective cohort study, adult patients who received intravenous vancomycin between January 2020 to January 2024 were examined. The RIFLE criteria was employed in identifying cases of AKI. Additionally, a pre-clinical vancomycin-associated nephrotoxicity model was established to provide insights into possible renal protective mechanisms. Patients receiving montelukast (n = 110) were compared to the control (n = 330); of which AKI was observed in 3 of 110 (2.7%) versus 35 of 330 (10.6%), respectively (P=0.01). A multivariate logistic regression analysis revealed that weight (OR: 1.02; 95% CI: 1.006 to 1.03; P-=0.005) and intensive care unit admission (OR: 6.88; 95% CI: 2.96 to 18.8; P<0.001) were independently associated with AKI, while montelukast (OR: 0.26; 95% CI: 0.06 to 0.77; P=0.03) and male gender were protective (OR: 0.41; 95% CI: 0.19 to 0.85; P=0.02). Our in vitro model also revealed that adjuvant montelukast can reduce injury to proximal tubule cells through activation of the p62/KEAP-1/HO-1 antioxidant pathway. Our study suggests that montelukast during vancomycin therapy may be protective against AKI, which may reduce patient harm and hospitalization costs. Further studies are warranted to validate our findings prospectively.