Associations of dysnatremias with mortality in chronic kidney disease

Background: Hyponatremia and hypernatremia are associated with death in the general population and those with chronic kidney disease (CKD). We studied the associations between dysnatremias, all-cause mortality and causes of death in a large cohort of Stage 3 and 4 CKD patients. Methods: We included 45 333 patients with Stage 3 and 4 CKDs followed in a large healthcare system. Associations between hyponatremia (< 136 mmol/L) and hypernatremia (> 145), and all-cause mortality and causes of death (cardiovascular, malignancy related and non-cardiovascular/nonmalignancy related) were studied using Cox proportional hazards and competing risk models. Results: Dysnatremias were found in 9.2% of the study population. In separate multivariable Cox proportional hazards models using baseline serum sodium levels and timedependent repeated measures, both hyponatremia and hypernatremia were associated with all-cause mortality. In the competing risk analyses, hyponatremia was significantly associated with increased risk for various cause-specific mortality categories [cardiovascular (hazard ratio, HR 1.16, 95% confidence interval, CI: 1.04, 1.30), malignancy related (HR 1.48, 95% CI: 1.33, 1.65) and non-cardiovascular/nonmalignancy deaths (HR 1.25, 95% CI: 1.13, 1.39)], while hypernatremia was significantly associated with higher noncardiovascular/ non- malignancy mortality only (HR 1.36, 95% CI: 1.08, 1.72). Conclusions: In those with CKD, hyponatremia was associated with all-cause mortality, cardiovascular, malignancy and noncardiovascular/ non- malignancy-related deaths. Hypernatremia was associated with all-cause and non-cardiovascular/nonmalignancy-related deaths. Further studies are needed to elucidate the mechanisms of differences in cause-specific death among CKD patients with hyponatremia and hypernatremia.