Reduction of vancomycin-associated acute kidney injury with montelukast.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.