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.
Keywords: Cardiovascular disease; Chloride; Chronic kidney disease; Electrolyte; Mortality; Sodium.