Protective factors against acute kidney injury in children exposed to diethylene glycol-contaminated medicines: A case-case-control analysis from The Gambia outbreak.

During The Gambia's 2022 diethylene glycol (DEG) outbreak, 82 children developed acute kidney injury (AKI) with 80% mortality. However, approximately 30% of children with documented DEG exposure did not develop AKI. Understanding protective factors could enable risk stratification and inform prophylactic interventions in future outbreaks. We conducted a case-case-control study among 321 children aged ≤8 years from six Gambian health regions. We compared exposed children who developed AKI (exposed-susceptible, n = 37) with exposed children who remained healthy (exposed-resistant, n = 16) and unexposed healthy children (n = 242). Multivariable logistic regression identified factors associated with AKI resistance among the 53 exposed children, adjusting for age, sex, and socioeconomic indicators. Sensitivity analyses included propensity score matching and stratification. Three factors were independently associated with reduced AKI risk: older age (adjusted OR=0.58 per year, 95% CI [0.36-0.92], p = .021), multivitamin supplementation (aOR=0.24, 95% CI [0.06-0.85], p = .028), and exposure to a single contaminated medicine (aOR=4.21 for ≥2 vs 1 medicine, 95% CI [1.12-16.85], p = .034). A dose-response relationship was observed, with AKI odds increasing 4-fold per additional contaminated medicine (p-trend = .018). Promethazine oral solution showed strongest toxicity (aOR=4.15, 95% CI [1.15-15.82]), consistent with highest DEG concentration (19.4 mg/mL). Multivitamin effects were strongest in children <18 months (aOR=0.15, 95% CI [0.02-0.81]). Findings remained robust across propensity score-matched analyses. Study limitations include small sample size of resistant children (n = 16), potential recall bias, wide confidence intervals, and possible residual confounding of multivitamin associations by socioeconomic and health literacy factors. Substantial heterogeneity exists in pediatric DEG susceptibility. Younger age, polypharmacy with multiple contaminated products, and absence of multivitamin supplementation were independently associated with increased AKI risk. These findings suggest potential targets for risk stratification and prophylactic strategies, though observed multivitamin associations require prospective validation with attention to confounding before clinical implementation.