Pre-dialysis Hyponatremia and Change in Serum Sodium Concentration During a Dialysis Session Are Significant Predictors of Mortality in Patients Undergoing Hemodialysis

Abstract

Background: Previous studies have shown that hyponatremia is associated with greater mortality in hemodialysis (HD) patients. However, there have been few reports regarding the importance of the change in serum sodium (SNa) concentration (ΔSNa) during dialysis sessions. To investigate the relationships of pre-dialysis hyponatremia and ΔSNa during a dialysis session with mortality, we analyzed data from a national registry of Japanese patients with end-stage kidney disease.

Methods: We identified 178,114 patients in the database who were undergoing HD 3 times weekly. The study outcome was 2-year all-cause mortality, and the baseline SNa concentrations were categorized into quintiles. We evaluated the relationships of SNa concentration and ΔSNa with mortality using Cox proportional hazards models.

Results: During a 2-year follow-up period, 25,928 patients died. Each 1-mEq/l reduction in pre-HD SNa concentration was associated with a cumulatively greater risk of all-cause mortality (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.05-1.06). In contrast, a larger ΔSNa was associated with higher all-cause mortality (HR for a 1-mEq/l increase in ΔSNa, 1.02; 95% CI 1.01-1.02). The combination of low pre-HD SNa concentration and large ΔSNa was also associated with higher mortality (HR 1.09; 95% CI 1.05-1.13). Participants with the lowest SNa concentration (≤136 mEq/L) and the highest ΔSNa (>4 mEq/L) showed higher mortality than those with an intermediate pre-HD SNa concentration (137-140 mEq/L) and the lowest ΔSNa (≤2 mEq/L).

Conclusions: Lower pre-HD SNa concentration and higher ΔSNa are associated with a greater risk of mortality in patients undergoing HD.

Keywords: hemodialysis; hyponatremia; mortality; prospective cohort.

Graphical abstract

Figure 1

Patient selection flow chart. SNa, serum sodium concentration.

Figure 2

Distribution of baseline serum sodium concentrations (SNa). (a) Serum sodium concentration before a hemodialysis (HD) session (pre-HD SNa). (b) Serum sodium concentration after an HD session (post-HD SNa). (c) Relationship between dialysate sodium concentration and pre-dialysis serum sodium concentration. Distribution of dialysate sodium concentration according to the mean predialysis serum sodium (Pre-HD SNa) category. Categories: 1, SNa ≤ 136 mEq/l; 2, 136 < SNa ≤ 138 mEq/l; 3, 138 < SNa ≤ 140 mEq/l; 4, 140 < SNa ≤ 141 mEq/l; 5, 141 mEq/l < SNa.

Figure 3

Kaplan–Meier plots for survival rates in the 5 groups during the 2-year follow-up period: univariate analysis. Categories: 1, SNa ≤ 136 mEq/l; 2, 136 < SNa ≤ 138 mEq/l; 3, 138 < SNa ≤ 140 mEq/l; 4, 140 < SNa ≤ 141 mEq/l; 5, 141 mEq/l < SNa.

Figure 4

Multivariable-adjusted restricted cubic spline plots of (a) the hazard ratios (HR) for all-cause mortality according to serum sodium concentration before an HD session (pre-HD SNa). Multivariable-adjusted restricted cubic spline plots of the odds ratios (OR) for (b) cerebral infarction and (c) lower limb amputation according to pre-HD SNa. The solid line represents the HR and OR, and the dotted line represents the 95% confidence interval. The multivariable-adjusted model (a) Cox model and (b) logistic model was adjusted for age, sex, duration of HD, length of an HD session, dialysate sodium, history of CVD, Hb, Alb, ΔSNa, Ca, P, T-Chol, Kt/V, CRP, nPCR, ΔBW%. Alb, serum albumin; BW, body weight; Ca, calcium; CRP, C-reactive protein; Hb, hemoglobin; HD, hemodialysis; P, phosphate; nPCR, normal protein catabolic rate; T.Chol., total cholesterol.

Figure 5

Multivariable-adjusted restricted cubic spline plots of (a) the hazard ratios (HR) for all-cause mortality according to post-dialysis serum sodium concentration (SNa)– pre-dialysis SNa (ΔSNa). Multivariable-adjusted restricted cubic spline plots of the odds ratios (OR) for (b) cerebral infarction and (c) lower limb amputation according to ΔSNa. The solid line represents the HR and OR, and the dotted line represents the 95% confidence interval. The multivariable-adjusted model (a) Cox model and (b) logistic model was adjusted for age, sex, duration of HD, length of an HD session, dialysate sodium, history of cardiovascular disease (CVD), Hb, Alb, SNa, Ca, P, T-Chol, Kt/V, CRP, nPCR, and ΔBW%. Alb, serum albumin; BW, body weight; Ca, calcium; CRP, C-reactive protein; Hb, hemoglobin; HD, hemodialysis; P, phosphate; nPCR, normal protein catabolic rate; T.Chol., total cholesterol.