Clinical research study
Mortality Associated with Low Serum Sodium Concentration in Maintenance Hemodialysis

https://doi.org/10.1016/j.amjmed.2010.07.029Get rights and content

Abstract

Background

Low serum sodium concentrations are associated with an increased risk of death in the general population, but causality is uncertain due to confounding from clinical conditions such as congestive heart failure and cirrhosis, in which hyponatremia results from elevated levels of arginine vasopressin.

Methods

To examine the association between predialysis serum sodium concentration and mortality in patients undergoing hemodialysis for end-stage renal disease, a condition in which arginine vasopressin does not affect water excretion and osmoregulation, we studied 1549 oligoanuric participants in the HEMO study, a randomized controlled trial of hemodialysis patients examining the effect of hemodialysis dose and flux. We used proportional hazards models to compare the risk of death according to predialysis serum sodium concentration.

Results

Considered as a continuous variable, each 4-mEq/L increment in baseline predialysis serum sodium concentration was associated with a hazard ratio for all-cause mortality of 0.84 (95% confidence interval (CI), 0.78-0.90). Multivariable adjustment for demographic, clinical, laboratory, and dialysis-specific covariates, including ultrafiltration volume, did not appreciably change the results (hazard ratio for all-cause mortality of 0.89; 95% CI, 0.82-0.96). The results also were consistent in time-updated analyses using repeated measures of serum sodium and other relevant covariates.

Conclusion

Lower predialysis serum sodium concentration is associated with an increased risk of death. Considering the unique physiology in the dialysis population, these findings raise the possibility that hyponatremia itself may be a causal determinant of mortality in the broader population. © 2011 Elsevier Inc. All rights reserved.

Section snippets

Study Population

This protocol was deemed exempt by the Partners Health Care Institutional Review Board. We performed a nonconcurrent cohort study of participants in the HEMO Study, the details of which have been previously published.4, 5, 6 Briefly, HEMO was a 2 × 2 factorial randomized control trial in which participants were assigned 1:1 to 1 of 2 levels of each dialysis dose and membrane flux (n = 1846). All participants were between 18 and 80 years old at study entry and had been receiving thrice weekly

Results

The primary cohort consisted of 1549 individuals. Overall, the mean (SD) age was 57.7 (14.2) years; 57% of participants were women; 64.2% were black. At baseline, mean (SD), median (interquartile range), minimum, and maximum predialysis serum sodium concentrations were 138.2 (4.0), 138 (136-141), 115, and 154 mEq/L, respectively (Figure 1). Over the course of the study, the median number of serum sodium measurements per subject was 5 (interquartile range 3-8). Considered over time, the overall

Discussion

The primary finding of this study is that among oligoanuric individuals on maintenance hemodialysis, lower serum sodium concentrations were associated with a greater risk of mortality. This association remained statistically significant upon adjustment for a number of demographic factors, comorbid disease, and laboratory measures that might plausibly confound the observed association. The association did not differ according to ultrafiltration volume or in those with or without congestive heart

Acknowledgment

The authors wish to thank the HEMO Study investigators and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) data repository for the data used in this study. The HEMO Study was performed by the HEMO Study investigators and supported by the NIDDK. This manuscript was not prepared in collaboration with the investigators of the HEMO Study and does not necessarily reflect the opinions or views of the HEMO Study or the NIDDK.

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    Funding: Norman S. Coplon Extramural Grant Program, Satellite Healthcare (investigator-initiated grant). Satellite Healthcare had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review, or approval of the manuscript. SSW is supported by DK075941; SMB is supported by DK079056.

    Conflict of Interest: Waikar and Curhan received grant support from Astellas for an investigator-initiated study of hyponatremia. Waikar participated in an advisory board meeting for Otsuka.

    Authorship: All authors had access to the data and a role in writing the manuscript.

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