Impact of serum sodium concentrations, and effect modifers on mortality in the Irish Health System

Background Abnormalities of serum sodium are associated with increased mortality risk in hospitalised patients, but it is unclear whether, and to what extent other factors infuence this relationship. We investigated the impact of dysnatraemia on total and cause-specifc mortality in the Irish health system while exploring the concurrent impact of age, kidney function and designated clinical work-based settings.

Methods A retrospective cohort study of 32,666 participants was conducted using data from the National Kidney Disease Surveillance System. Hyponatraemia was defned as<135 mmol/L and hypernatraemia as>145 mmol/L with normal range 135–145 mmol/L. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR’s) and 95% Confdence Intervals (CIs) while penalised spline models further examined patterns of risk.

Results There were 5,114 deaths (15.7%) over a median follow up of 5.5 years. Dysnatraemia was present in 8.5% of patients overall. In multivariable analysis, both baseline and time-dependent serum sodium concentrations exhibited a U-shaped association with mortality. Hyponatremia was signifcantly associated with increased risk for cardiovascular [HR 1.38 (1.18–1.61)], malignant [HR: 2.49 (2.23–2.78)] and non-cardiovascular/non-malignant causes of death [1.36 (1.17–1.58)], while hypernatremia was signifcantly associated with cardiovascular [HR: 2.16 (1.58–2.96)] and non-cardiovascular/ non-malignant deaths respectively [HR: 3.60 (2.87–4.52)]. The sodium-mortality relationship was signifcantly infuenced by age, level of kidney function and the clinical setting at baseline (P<0.001). For hyponatraemia, relative mortality risks were signifcantly higher for younger patients (interaction term P<0.001), for patients with better kidney function, and for patients attending general practice [HR 2.70 (2.15–3.36)] than other clinical settings. For hypernatraemia, age and kidney function remained signifcant efect modifers, with patients attending outpatient departments experiencing the greatest risk [HR 9.84 (4.88–18.62)] than patients who attended other clinical locations. Optimal serum sodium thresholds for mortality varied by level of kidney function with a fattening of mortality curve observed for patients with poorer kidney function.

Conclusion Serum sodium concentrations outside the standard normal range adversly impact mortality and are associated with specifc causes of death. The thresholds at which these risks appear to vary by age, level of kidney function, and are modifed in specifc clinical settings within the health system.