Low serum sodium concentrations are associated with an increased risk of death in the general population, but causality is uncertain due to confounding from clinical conditions such as congestive heart failure and cirrhosis, in which hyponatremia results from elevated levels of arginine vasopressin.

To examine the association between predialysis serum sodium concentration and mortality in patients undergoing hemodialysis for end-stage renal disease, a condition in which arginine vasopressin does not affect water excretion and osmoregulation, we studied 1549 oligoanuric participants in the HEMO study, a randomized controlled trial of hemodialysis patients examining the effect of hemodialysis dose and flux. We used proportional hazards models to compare the risk of death according to predialysis serum sodium concentration.

Considered as a continuous variable, each 4-mEq/L increment in baseline predialysis serum sodium concentration was associated with a hazard ratio for all-cause mortality of 0.84 (95% confidence interval (CI), 0.78-0.90). Multivariable adjustment for demographic, clinical, laboratory, and dialysis-specific covariates, including ultrafiltration volume, did not appreciably change the results (hazard ratio for all-cause mortality of 0.89; 95% CI, 0.82-0.96). The results also were consistent in time-updated analyses using repeated measures of serum sodium and other relevant covariates.

Lower predialysis serum sodium concentration is associated with an increased risk of death. Considering the unique physiology in the dialysis population, these findings raise the possibility that hyponatremia itself may be a causal determinant of mortality in the broader population. © 2011 Elsevier Inc. All rights reserved.