Abstract
BACKGROUND: A consistent association between low serum sodium measured at a single-point-in-time (baseline sodium) and higher mortality has been observed in hemodialysis patients. We hypothesized that both low and high time-varying sodium levels (sodium levels updated at quarterly intervals as a proxy of short-term exposure) are independently associated with higher death risk in hemodialysis patients. METHODS: We examined the association of baseline and time-varying pre-dialysis serum sodium levels with all-cause mortality among adult incident hemodialysis patients receiving care from a large national dialysis organization during January 2007-December 2011. Hazard ratios were estimated using multivariable Cox models accounting for case-mix+laboratory covariates and incrementally adjusted for inter-dialytic weight gain, blood urea nitrogen and glucose. RESULTS: Among 27 180 patients, a total of 7562 deaths were observed during 46 194 patient-years of follow-up. Median (IQR) at-risk time was 1.4 (0.6, 2.5) years. In baseline analyses adjusted for case-mix+laboratory results, sodium levels <138 mEq/L were associated with incrementally higher mortality risk, while the association of sodium levels ≥140 mEq/L with lower mortality reached statistical significance only for the highest level of pre-dialysis sodium (reference: 138-<140 mEq/L). In time-varying analyses, we observed a U-shaped association between sodium and mortality such that sodium levels <138 and ≥144 mEq/L were associated with higher mortality risk. Similar patterns were observed in models incrementally adjusted for inter-dialytic weight gain, blood urea nitrogen and glucose. CONCLUSIONS: We observed a U-shaped association of time-varying pre-dialysis serum sodium and all-cause mortality in hemodialysis patients, suggesting that both hypo- and hypernatremia carry short-term risk in this population.