Associations Between Carvedilol Use and Outcomes in Critically Ill Patients with Acute Kidney Injury: A Multicenter Retrospective Cohort Study

Background: Acute kidney injury (AKI) is one of the leading causes of in-hospital mortality in critically ill patients, with few treatment options other than supportive care. While preclinical studies suggest carvedilol may offer renal protection, its effect on outcomes in this population remains unclear. Methods: This retrospective study included 26,230 adult patients with AKI from the MIMIC-IV database to evaluate outcomes associated with carvedilol use. The primary endpoint was 30-day all-cause mortality. Secondary endpoints included ICU and in-hospital mortality, renal replacement therapy (RRT) requirement, renal function recovery, and ICU/hospital length of stay. Additional outcomes assessed were the incidence of hyperkalemia, the need for vasopressors, and mortality at 90, 180, and 360 days. Multivariable Cox proportional hazards models and logistic regression were employed, along with propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) to ensure robustness. A separate cohort of 36793 critically ill patients with AKI from the eICU Collaborative Research Database was analyzed for the external validation. Results: Carvedilol intervention was associated with significantly lower 30-day mortality (adjusted HR 0.53, 95% CI 0.44–0.65; p<0.001), ICU mortality (adjusted HR 0.37, 95% CI 0.26–0.50; p<0.001) and in-hospital mortality (adjusted HR 0.42, 95% CI 0.32–0.54; p<0.001), with sustained benefits up to 360 days (adjusted HR 0.71, 95% CI 0.63–0.880; p<0.001). These findings were supported by external validation in the eICU cohort, where carvedilol was independently associated with reduced ICU and in-hospital mortality (adjusted HRs 0.52 and 0.64, respectively; both p<0.001). Carvedilol-treated patients had higher rates of renal function recovery (adjusted OR 1.29, 95% CI 1.09–1.54; p<0.001), shorter ICU stays (median 4.1 vs 4.2 days, p=0.012), and no increased risk of hyperkalemia (p>0.05). Conclusion: In critically ill patients with AKI, carvedilol use was associated with improved short- and long-term survival, without an increased risk of hyperkalemia.