Protective Effect of Vitamin E Against Vancomycin‐Induced Nephrotoxicity: A Large‐Scale Electronic Medical Record Study From Japan

Vancomycin (VCM) is essential for treating methicillin-resistant Staphylococcus aureus infections, but its use is limited by vancomycin-induced nephrotoxicity (VIN). Although preclinical and small clinical studies suggest a protective role for vitamin E, real-world evidence remains limited. We conducted a retrospective cohort study using a large-scale Japanese electronic medical record database including adult patients who received intravenous VCM between 1996 and 2022. VIN was defined according to Kidney Disease Improving Global Outcomes criteria. The association between concomitant vitamin E use and VIN was evaluated using propensity score matching based on logistic regression and light gradient boosting machine models, followed by Kaplan-Meier analysis and Cox proportional hazards regression. Robustness was examined using three analytical strategies, including adjustment for concomitant medications. Among 12 411 eligible patients, 2267 (18.3%) developed VIN and 116 (0.9%) received vitamin E. After matching, vitamin E use was associated with a 10% lower incidence of VIN. Kaplan-Meier analysis showed significantly lower cumulative incidence in the vitamin E group in two approaches. Across 63 Cox models, vitamin E consistently demonstrated a protective trend. These findings support the potential preventive role of vitamin E in maintaining VCM therapy.