Lower serum sodium level predicts higher risk of infection-related hospitalization in maintenance hemodialysis patients: an observational cohort study

Background: Hyponatremia is associated with increased mortality in chronic kidney disease with and without end-stage renal disease (ESRD). Increasing evidence suggests that hyponatremia is not only a marker of severe underlying disease, but also a direct contributor to mortality. However, specific pathogenesis or diseases contributing to mortality in the hyponatremic population are unknown. This study aimed to clarify the relationship between serum sodium level (sNa) and infection risk in ESRD patients. Methods: This observational cohort study included 332 patients on maintenance hemodialysis in our dialysis unit in May 2009. The mean of 3 monthly measurements of glucose-corrected sNa before each dialysis session in May, June, and July 2009 was applied as baseline sNa. The primary endpoint was first infection-related hospitalization (IRH), and the secondary endpoint was death of any cause. Data were analyzed using Cox hazards modeling, adjusted for baseline demographics and characteristics, or laboratory data. Patients were followed until transfer, kidney transplantation, death, or study end on January 31, 2013. Results: Mean sNa was 138.9 mEq/L (1st tertile: <138.0, n = 104; 2nd tertile: 138.0-140.0, n = 116; 3rd tertile: >140.0, n = 112). During 39.5 months' mean follow-up, 57 patients experienced IRH (56.4/1,000 patient-years overall; 89.7/1,000 in 1st tertile; 57.9/1,000 in 2nd tertile; 28.0/1,000 in 3rd tertile), and 68 patients died. The hazard ratio (HR) for IRH was higher for the 1st and 2nd tertiles than the 3rd tertile (unadjusted HR, 3.20; 95% confidence interval (CI), 1.54-6.64; p = 0.002; adjusted HR, 2.36; 95% CI, 1.10-5.04; p = 0.027; and unadjusted HR, 2.07; 95% CI, 0.98-4.40; p = 0.058; adjusted HR, 2.11; 95% CI, 0.99-4.51; p = 0.054 respectively). In a continuous model, higher sNa was associated with lower risk of IRH (adjusted HR, 0.90; 95% CI, 0.81-0.99; p = 0.040), and lower all-cause mortality (adjusted HR, 0.91; 95% CI, 0.83-1.00; p = 0.049). Conclusions: Lower sNa is an independent predictor of higher risk for infection-related hospitalization in maintenance hemodialysis patients. Infectious disease may partially account for the increased mortality observed in the hyponatremic population with ESRD.