Connie M Rhee1, Vanessa A Ravel1, Juan Carlos Ayus2, John J Sim3, Elani Streja4, Rajnish Mehrotra5, Alpesh N Amin6, Danh V Nguyen6, Steven M Brunelli7, Csaba P Kovesdy8, Kamyar Kalantar-Zadeh9. 1. Harold Simmons Center for Chronic Disease Research and Epidemiology, University of California Irvine, Orange, CA, USA. 2. Renal Consultants of Houston, Houston, TX, USA. 3. Kaiser Permanente of Southern California, Los Angeles, CA, USA. 4. 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. 5. Kidney Research Institute and Harborview Medical Center, Division of Nephrology, University of Washington, Seattle, WA, USA. 6. Department of Medicine, University of California Irvine, Orange, CA, USA. 7. DaVita Clinical Research, Minneapolis, MN, USA. 8. University of Tennessee Health Science Center, Memphis, TN, USA Memphis Veterans Affairs Medical Center, Memphis, TN, USA. 9. Harold Simmons Center for Chronic Disease Research and Epidemiology, University of California Irvine, Orange, CA, USA Renal Consultants of Houston, Houston, TX, USA.
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.
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 ureanitrogen 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 ureanitrogen 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.
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