Pre-dialysis serum sodium and mortality in a national incident hemodialysis cohort

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.

Keywords: hemodialysis; hypernatremia; hyponatremia; mortality; sodium.

FIGURE 1:

Associations between baseline (A) and time-varying (B) sodium level, and all-cause mortality in incident hemodialysis patients. Unadjusted model adjusted for patients' calendar quarter of entry. Case-mix model adjusted for covariates in the unadjusted model, plus age, sex, race/ethnicity, insurance, vascular access, alcohol use, diabetes, congestive heart failure, atherosclerotic disease, other cardiovascular disease, cerebrovascular disease, hypertension, chronic obstructive pulmonary disease, human immunodeficiency virus and malignancy. Case-mix+IDWG model adjusted for covariates in the case-mix model, plus IDWG. Case-mix+laboratory model adjusted for covariates in the case-mix model, plus body mass index, spKt/V, residual urea clearance, serum albumin, serum creatinine, total iron binding capacity, serum bicarbonate, ferritin, hemoglobin, iron saturation, phosphorus, parathyroid hormone, white blood cell count and normalized protein catabolic rate. Case-mix+laboratory+IDWG model adjusted for covariates in the case-mix+laboratory, plus IDWG. Case-mix+extended laboratory+IDWG model adjusted for covariates in the case-mix+laboratory+IDWG model, plus glucose and blood urea nitrogen.

FIGURE 2:

Associations between baseline sodium–IDWG combinations and all-cause mortality in incident hemodialysis patients. (A) Adjusted for unadjusted model covariates: patients' calendar quarter of entry. (B) Adjusted for case-mix model covariates: unadjusted model covariates, plus age, sex, race/ethnicity, insurance, vascular access, alcohol use, diabetes, congestive heart failure, atherosclerotic disease, other cardiovascular disease, cerebrovascular disease, hypertension, chronic obstructive pulmonary disease, human immunodeficiency virus and malignancy. (C) Adjusted for case-mix+laboratory covariates: case-mix covariates, plus body mass index, spKt/V, residual urea clearance, serum albumin, serum creatinine, total iron binding capacity, serum bicarbonate, ferritin, hemoglobin, iron saturation, phosphorus, parathyroid hormone, white blood cell count and normalized protein catabolic rate.

FIGURE 3:

Associations between time-varying sodium–IDWG combinations and all-cause mortality in incident hemodialysis patients. (A) Adjusted for unadjusted model covariates: patients' calendar quarter of entry. (B) Adjusted for case-mix model covariates: unadjusted model covariates, plus age, sex, race/ethnicity, insurance, vascular access, alcohol use, diabetes, congestive heart failure, atherosclerotic disease, other cardiovascular disease, cerebrovascular disease, hypertension, chronic obstructive pulmonary disease, human immunodeficiency virus and malignancy. (C) Adjusted for case-mix+laboratory model covariates: case-mix model covariates, plus body mass index, spKt/V, residual urea clearance, serum albumin, serum creatinine, total iron binding capacity, serum bicarbonate, ferritin, hemoglobin, iron saturation, phosphorus, parathyroid hormone, white blood cell count and normalized protein catabolic rate.

FIGURE 4:

Associations between baseline (A and B) and time-varying (C and D) sodium level, and all-cause mortality across clinically relevant subgroups of incident hemodialysis patients. (A and C) Stratified by subgroups of sociodemographics and comorbidities. (B and D) Stratified by subgroups of laboratory results. Unadjusted model adjusted for patients' calendar quarter of entry. Case-mix model adjusted for covariates in the unadjusted model, plus age, sex, race/ethnicity, insurance, vascular access, alcohol use, diabetes, congestive heart failure, atherosclerotic disease, other cardiovascular disease, cerebrovascular disease, hypertension, chronic obstructive pulmonary disease, human immunodeficiency virus and malignancy. CHF, congestive heart failure; BMI, body mass index; IDWG, inter-dialytic weight gain; ALB, albumin; CR, creatinine; CA, calcium; NPCR, normalized protein catabolic rate; PHOS, phosphate; PTH, parathyroid hormone level.