title: Pre-dialysis serum sodium and mortality in a national incident hemodialysis cohort.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Harold Simmons Center for Chronic Disease Research and Epidemiology, University of California Irvine, Orange, CA, USA.
authors.forename: Connie M
authors.initials: CM
authors.lastname: Rhee
authors.affiliation: Harold Simmons Center for Chronic Disease Research and Epidemiology, University of California Irvine, Orange, CA, USA.
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Ravel
authors.affiliation: Renal Consultants of Houston, Houston, TX, USA.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Ayus
authors.affiliation: Kaiser Permanente of Southern California, Los Angeles, CA, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: Sim
authors.affiliation: Harold Simmons Center for Chronic Disease Research and Epidemiology, University of California Irvine, Orange, CA, USA Veterans Affairs Long Beach Healthcare System, Long Beach, CA, USA.
authors.forename: Elani
authors.initials: E
authors.lastname: Streja
authors.affiliation: Kidney Research Institute and Harborview Medical Center, Division of Nephrology, University of Washington, Seattle, WA, USA.
authors.forename: Rajnish
authors.initials: R
authors.lastname: Mehrotra
authors.affiliation: Department of Medicine, University of California Irvine, Orange, CA, USA.
authors.forename: Alpesh N
authors.initials: AN
authors.lastname: Amin
authors.affiliation: Department of Medicine, University of California Irvine, Orange, CA, USA.
authors.forename: Danh V
authors.initials: DV
authors.lastname: Nguyen
authors.affiliation: DaVita Clinical Research, Minneapolis, MN, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Brunelli
authors.affiliation: University of Tennessee Health Science Center, Memphis, TN, USA Memphis Veterans Affairs Medical Center, Memphis, TN, USA.
authors.forename: Csaba P
authors.initials: CP
authors.lastname: Kovesdy
authors.affiliation: Harold Simmons Center for Chronic Disease Research and Epidemiology, University of California Irvine, Orange, CA, USA Renal Consultants of Houston, Houston, TX, USA.
authors.forename: Kamyar
authors.initials: K
authors.lastname: Kalantar-Zadeh
mesh_terms: D002423:Cause of Death / Q000639:trends; D005260:Female; D006801:Humans; D006955:Hypernatremia / Q000097:blood / Q000209:etiology / Q000401:mortality*; D007010:Hyponatremia / Q000097:blood / Q000209:etiology / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000401:mortality*; D051437:Renal Insufficiency / Q000097:blood / Q000401:mortality / Q000628:therapy*; D018570:Risk Assessment / Q000379:methods*; D012964:Sodium / Q000097:blood*; D015996:Survival Rate / Q000639:trends; D014481:United States / Q000453:epidemiology
chemical_list: D012964:Sodium
keywords: hemodialysis; hypernatremia; hyponatremia; mortality; sodium