Multifactorial attribution for vancomycin‐associated acute kidney injury

AIM: Vancomycin is a cornerstone therapy for severe gram-positive infections but is known to cause acute kidney injury (AKI). Although AKI risk is concentration dependent, its heterogeneous nature in real-world polypharmacy settings remains poorly understood. We assessed the association between vancomycin exposure and AKI while identifying heterogeneous risk patterns across patient subgroups. METHODS: We conducted a retrospective analysis of electronic health records of adults receiving vancomycin from 2019 to 2023 at a tertiary medical centre in southern Taiwan. Patients aged ≥20 years who received vancomycin for ≥3 consecutive days were included. The primary outcome was vancomycin-associated AKI. The relationship between trough concentrations and AKI risk was analysed using logistic regression. Conditional average treatment effect (CATE) analysis using the X-Learner framework estimated heterogeneous risk differences across subgroups by comorbidities and concomitant medications. RESULTS: Among 1611 patients (mean age 65.8 years), 374 (23.2%) developed AKI. Each 1 mg/L increase in trough concentration increased AKI odds by 8% (odds ratio 1.08; 95% confidence interval 1.06-1.10). Patients with high troughs (>15.5 mg/L) had a 31% higher absolute risk of AKI. The CATE analysis revealed substantial heterogeneity: Co-administration of β-lactams (piperacillin and meropenem) and loop diuretics increased vancomycin-attributable AKI risk, with varying risk levels across subgroups. CONCLUSION: The risk of vancomycin-associated AKI varied across subgroups and was influenced by concomitant medications. Loop diuretics, piperacillin and meropenem affected the association between vancomycin exposure and AKI. These findings highlight the need for comprehensive risk assessment considering medication profiles and nephrotoxic potential, rather than vancomycin concentration alone.