Association of serum chloride level with mortality and cardiovascular events in chronic kidney disease: the CKD-ROUTE study.

Background: Electrolyte abnormalities, particularly dysnatremia, are independent predictors of adverse outcome in individuals with and without renal failure. However, the association of serum chloride level (Cl) with mortality or risk of cardiovascular (CV) events in chronic kidney disease (CKD) remains unclear. Methods: This prospective cohort study included 923 pre-dialysis CKD G2-G5 patients among the participants of the CKD Research of Outcomes in Treatment and Epidemiology (CKD-ROUTE) study, who newly visited 16 nephrology centers. The primary outcome was a composite of overall death and CV events, and the secondary outcome was overall death. Data were analyzed using the Cox hazards model with adjustment for potential confounders. Results: Median Cl was 106.0 mEq/L at enrollment [quartile (Q) 1: ≤103.9, n = 207; Q2: 104.0-105.9, n = 207; Q3: 106.0-108.0, n = 289; Q4: ≥108.1, n = 220]. During a median follow-up of 33 months, there were 98 CV events, 66 deaths, and 154 composite outcomes. The hazard ratio (HR) for the composite outcome was higher for Q1 than Q3 [HR 1.72; 95 % confidence interval (CI) 1.08-2.72; P = 0.022]. As a continuous variable in a subset of patients whose Cl was ≤106.0 mEq/L, higher Cl was associated with lower risk of the composite outcome (HR 0.93; 95 % CI 0.87-0.99; P = 0.023). HR for all-cause mortality was also higher for Q1 than Q3 (HR 2.48; 95 % CI 1.22-5.03; P = 0.012). Conclusion: Low Cl was associated with increased mortality and risk of CV events in pre-dialysis CKD patients. Cl may be an additional prognostic indicator in CKD. [ABSTRACT FROM AUTHOR]