Serum sodium level predicts death in chronic kidney disease patients
MedWire News: Abnormally high or low levels of serum sodium are associated with increased mortality in patients with chronic kidney disease (CKD), results of a large study among US veterans show.
"These associations were linearly proportional with the severity of the underlying hyponatremia and hypernatremia, and were independent from comorbid conditions such as CHF [congestive heart failure] or liver disease," report Csaba Kovesdy (Salem Veterans Affairs Medical Center, Charlottesville, Virginia, USA) and colleagues in Circulation.
The researchers explain that the association of serum sodium concentration with mortality in CKD patients is not well characterized, even though these patients may be more susceptible to the development of dysnatremias due to their diminished ability to maintain water homeostasis.
To address this, Kovesdy and team examined the association of serum sodium levels measured repeatedly over time with all-cause mortality in a nationally representative cohort of 655,493 US veterans with nondialysis-dependent CKD.
The mean age of the cohort at baseline was 73.9 years, 86.6% of patients were White, and 14.6% had CHF.
Hyponatremia (serum sodium <136 mEq/L) and hypernatremia (serum sodium >145 mEq/L) were present in 13.5% and 2.0% of patients, respectively, at baseline.
During a median follow-up period of 5.5 years, 25.8% of patients had at least one episode of hyponatremia, 7.0% had at least one episode of hypernatremia, and 29.6% died, giving a mortality rate of 62.5 per 1000 patient-years.
The researchers observed a U-shaped association between serum sodium level and mortality; patients with a sodium level of 136-140 mEq/L had the lowest mortality, while those with lower or higher levels had significantly higher mortality.
Specifically, compared with a serum sodium level of 136-145 mEq/L, levels below 130 mEq/L, 130-135.9 mEq/L, 145.1-150.0 mEq/L, and 150.0 mEq/L or higher were independently associated with a 1.93-, 1.28-, 1.33-, and 1.56-fold increased risk for mortality, respectively, after controlling for potential confounders.
When the researchers conducted a time-dependent analysis, they observed weak or no effects associated with baseline serum levels but stronger associations with time-varying sodium categories, "suggesting that both hypo- and hypernatremia represent acute (short-term), rather than chronic (long-term) risk factors for mortality."
They add that it is possible that hyponatremia and hypernatremia are merely surrogate markers of more severe disease states, but the associations they observed were also present in subgroup analyses among patients with and without CHF, liver disease, malignancy, and depression. This "makes it more likely that abnormal serum sodium level has an independent effect on survival."
The researchers say that their findings establish "hypo- and hypernatremia as robust outcome predictors in patients with all stages of CKD."
They conclude that abnormal serum sodium levels "could be considered as treatment targets that need to be tested in clinical trials."
By Laura Cowen