Association of Dexmedetomidine Exposure with Long-Term Mortality in Patients with Dialysis-Requiring Acute Kidney Injury: A Propensity Score–Matched Retrospective Cohort Study

Purpose: Patients surviving dialysis-requiring acute kidney injury (AKI-D) have high long-term mortality, yet effective pharmacologic interventions are limited. Dexmedetomidine (DEX) has demonstrated organ-protective properties, but its association with long-term outcomes in patients with AKI-D remains unclear. Methods: We conducted a propensity score-matched retrospective cohort study using the TriNetX database. Adults with AKI-D during intensive care unit (ICU) stay were classified into DEX exposure (within 1 month after AKI) or control groups. A 90-day landmark design was applied to reduce immortal time bias and reverse causation, with follow-up initiated thereafter. The primary outcome was 2-year mortality; secondary outcomes included end-stage renal disease (ESRD), eGFR decline < 30 mL/min/1.73m 2 , ICU readmission, pneumonia, and sepsis. Results: After matching, 6,354 patients remained per group. DEX exposure was associated with lower 2-year mortality (10.0% vs 14.6%; Hazard ratioHR 0.64, 95% CI 0.58– 0.71, p< 0.001), reduced ESRD progression (14.1% vs 16.2%; HR 0.80, 95% CI 0.73– 0.88, p< 0.001), and lower eGFR decline (19.4% vs 21.8%; HR 0.83, 95% CI 0.77– 0.90, p< 0.001). No significant differences were observed for ICU readmission (HR 0.97, 95% CI 0.89– 1.06, p=0.55), pneumonia (HR 1.05, 95% CI 0.94– 1.16, p=0.414), or sepsis (HR 1.07, 95% CI 0.97– 1.18, p=0.199). The mortality benefit persisted during 2– 5 year follow-up (HR 0.81, 95% CI 0.69– 0.96, p=0.012). Sensitivity analyses using contemporary data, medical center restriction, and a benzodiazepine active comparator, along with subgroup analyses by age and sex, demonstrated consistent associations. Early DEX initiation (within 1 week) showed stronger associations with favorable outcomes compared with delayed exposure (1– 4 weeks). Conclusion: DEX exposure following AKI-D in critical care settings was associated with reduced long-term mortality and lower risks of renal deterioration. These findings provide a strong rationale for prospective randomized controlled trials to evaluate the causal effects of dexmedetomidine in this high-risk population. Keywords: dexmedetomidine, acute kidney injury, dialysis, mortality, end-stage renal disease, critical care