High and low serum sodium levels measured prior to hemodialysis (HD) are associated with an elevated mortality risk, according to a new study.

In a study of 27,180 HD patients, of whom 7,562 died during 46,194 patient-years of follow-up, researchers found that pre-dialysis serum sodium levels below 138 mEq/L and 144 mEq/L or higher were associated with a significantly increased risk of death compared to a reference range of 138 to 140 mEq/L.

Specifically, in the lower sodium range, patients with sodium level categories of less than 130, 130 to less than 132, 132 to less than 134, 134 to less than 136, and 136 to less than 138 mEq/L had a 2.3, 1.7, 1.5, 1.3, and 1.1-fold increased risk of death, respectively, in analyses of time-varying sodium levels, even after accounting for case-mix characteristics, laboratory test results, and other potential confounders. All of these associations were statistically significant.

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In the higher sodium range, patients with a sodium level of 142 to less than 144 mEq/L and 144 mEq/L or higher had a 1.1 and 1.5-fold increased death risk, respectively. Only a sodium level of 144 mEq/L or higher was associated with a statistically significant increased risk of death.

“To our knowledge, ours is the first study that has shown a U-shaped association between time-varying sodium level and mortality in hemodialysis patients,” lead researcher Connie M. Rhee, MD, MSc, of the University of California Irvine, and colleagues reported online ahead of print in Nephrology Dialysis Transplantation.

She and her collaborators offered some possible explanations as to how sodium abnormalities may directly predispose to HD patient mortality. For example, hypo- or hypernatremia may result in equilibrium problems, falls, gait disturbances, fractures, and subsequent mortality risk, they stated. Hyponatremia may further predispose to fracture risk by decreasing bone mineral density, volume, and metabolism. They additionally stated that dysnatremia may be directly toxic to the cerebrovascular and cardiovascular systems, and highlighted data suggesting that hyponatremia may also lead to heightened infection risk.

Dr. Rhee’s group also pointed out that hyponatremia could be a marker of underlying conditions that are associated with increased mortality risk in HD, such as protein-energy wasting, poor solute intake, and non-adherence with dietary fluid restriction and volume overload associated with maladaptive cardiac changes and high fluid removal rates during dialysis.