Association between serum chloride levels with mortality in critically ill patients with acute kidney injury: An observational multicenter study employing the eICU database

OBJECTIVE: The effect of the serum chloride (Cl) level on mortality in critically ill patients with acute kidney injury (AKI) remains unknown. We sought an association between mortality and serum Cl. METHODS: We identified AKI patients in the eICU Collaborative Research Database from 2014 to 2015 at 208 US hospitals. The outcomes included in-hospital and intensive care unit (ICU) mortality. Time-varying covariates Cox regression models and the Kaplan-Meier (K-M) curves were used to assess the association between serum Cl levels and mortality. Multivariable adjusted restricted cubic spline models were used to analyze the potential nonlinear relationship between mortality and serum Cl. RESULTS: In total, 4,234 AKI patients were included in the study. Compared with normochloremia (98≤chloride<108mEq/L), hypochloremia (Cl<98mEq/L) was associated with mortality (adjusted hazard ratio [HR] for in-hospital mortality 1.46, 95% confidence interval [CI] 1.20–1.80, P = 0.0003; adjusted HR for ICU mortality 1.37, 95% CI 1.05–1.80, P = 0.0187). Hyperchloremia showed no significant difference in mortality compared to normochloremia (adjusted HR for in-hospital mortality 0.89, 95% CI 0.76–1.04, P = 0.1438; adjusted HR for ICU mortality 0.87, 95% CI 0.72–1.06, P = 0.1712). Smoothing curves revealed continuous non-linear associations between serum Cl levels and mortality. The K-M curve showed that patients with hypochloremia presented with a lower survival rate. CONCLUSIONS: Lower serum Cl levels after ICU admission was associated with increased in-hospital and ICU mortality in critically ill patients with AKI. The results should be verified in well-designed prospective studies.