Changes in serum sodium concentration during hemodialysis is a predictor of mortality and cardio-cerebrovascular event

Figures & data

Table 1. Baseline characteristics of the participants.

Characteristics	Total n = 110	Pre-HD SNa < 138 n = 44	Pre-HD SNa ≥ 138 n = 66	p
Age (years)	57.1 ± 12.43	58.07 ± 11.04	56.45 ± 13.32	0.507
Male, n (%)	55 (50.0)	22 (50.0)	33 (50.0)	1.000
BMI (kg/m2)	22.72 ± 3.76	23.11 ± 3.28	22.46 ± 4.05	0.377
Smoking habit, n (%)	39 (35.5)	16 (36.4)	23 (34.8)	1.000
Drinking habit, n (%)	40 (36.4)	11 (25.0)	29 (43.9)	0.069
Comorbidities, n (%)
DM	24 (21.8)	11 (25.0)	13 (19.7)	0.671
Hypertension	108 (98.2)	44 (100.0)	64 (97.0)	0.662
CCVD	18 (16.4)	4 (9.1)	14 (21.2)	0.155
Malignant tumor	13 (11.8)	2 (4.5)	11 (16.7)	0.104
Dialysis parameters
UF (L)	2.31 ± 0.98	2.64 ± 0.93	2.10 ± 0.96	0.006
Dry weight (kg)	62.15 ± 11.97	61.96 ± 9.43	62.27 ± 13.42	0.900
Kt/V	1.42 ± 0.25	1.42 ± 0.20	1.43 ± 0.28	0.885
Vintage (months)	72.83 ± 59.99	71.55 ± 60.07	73.68 ± 60.39	0.856
Laboratory parameters
Alb (g/L)	39.77 ± 3.95	38.98 ± 4.33	40.30 ± 3.61	0.084
Hb (g/L)	112.56 ± 13.45	113.73 ± 14.12	111.79 ± 13.04	0.461
Cr (umol/L)	974.65 ± 226.85	948.2 ± 211.44	992.27 ± 236.50	0.320
BUN (mmol/L)	27.86 ± 5.39	28.08 ± 4.95	27.72 ± 5.70	0.736
Na (mmol/L)	137.9 ± 3.12	134.89 ± 1.77	139.91 ± 1.99	<0.001
K (mmol/L)	5.08 ± 0.62	5.18 ± 0.63	5.02 ± 0.61	0.187
Ca (mmol/L)	2.26 ± 0.20	2.25 ± 0.21	2.27 ± 0.18	0.532
P (mmol/L)	1.86 ± 0.46	1.89 ± 0.46	1.84 ± 0.46	0.605
PTH (pg/mL)	481.54 ± 503.28	499.11 ± 498.06	469.83 ± 510.19	0.767
UA (umol/L)	433.28 ± 83.07	423.8 ± 95.01	439.61 ± 74.15	0.330
CRP (mg/L)	6.08 ± 11.63	8.76 ± 15.77	4.30 ± 7.37	0.048
Ferr (ng/mL)	445.08 ± 330.76	421.18 ± 349.25	461.02 ± 319.57	0.539
TG (mmol/L)	1.51 ± 0.87	1.61 ± 0.94	1.45 ± 0.82	0.355
TC (mmol/L)	4.22 ± 0.99	4.16 ± 0.86	4.26 ± 1.07	0.608
HDL-C (mmol/L)	1.11 ± 0.36	1.09 ± 0.39	1.12 ± 0.33	0.706
LDL-C (mmol/L)	2.4 ± 0.77	2.31 ± 0.7	2.46 ± 0.82	0.319

Continuous variables were presented as mean ± SD; categorical variables were presented as n (%). HD: hemodialysis; SNa: serum sodium; BMI: body mass index; DM: diabetes mellitus; CCVD cardio-cerebrovascular disease; UF,: ultrafiltration; Alb: albumin; Hb: hemoglobin; Cr: creatinine; BUN: blood urea nitrogen; Na sodium; K, potassium; Ca: calcium; P: phosphorus; PTH: parathyroid hormone; UA: uric acid; CRP: C-reactive protein; Ferr: ferritin; TG: triglyceride; TC: total cholesterol; HDL-C: high density lipoprotein-cholesterol; LDL: low density lipoprotein-cholesterol.

Table 2. Pre-HD SNa and ΔSNa of the participants.

Duration	Pre-HD SNa (mmol/L)	Post-HD SNa (mmol/L)	Na gradient (mmol/L)	ΔSNa (mmol/L)
Baseline	137.9 ± 3.12	137.07 ± 2.20	0.10 ± 3.12	−0.83 ± 2.86
1-year	137.83 ± 2.32	137.18 ± 1.60	0.17 ± 2.32	−0.65 ± 1.87
2-year	137.68 ± 2.26	137.22 ± 1.50	0.32 ± 2.26	−0.46 ± 1.79
3-year	137.51 ± 2.23	137.51 ± 2.23	0.49 ± 2.23	−0.40 ± 1.75

Pre-HD SNa, pre-hemodialysis serum sodium; post-HD SNa, post-hemodialysis serum sodium; Na gradient, the disparity between the dialysate sodium concentration and the pre-HD SNa (dialysate Na – pre-HD SNa); ΔSNa, the change in SNa concentration (post-HD SNa – pre-HD SNa).

Table 3. Cox proportional hazards models of pre-HD SNa for all-cause mortality and cardio-cerebrovascular event.

		Unadjusted				Model 1				Model 2
	HR	95% CI	P	AUC	HR	95% CI	P	AUC	HR	95% CI	P	AUC
All-cause Mortality
Baseline pre-HD SNa	0.99	0.89–1.10	0.837	0.493	0.97	0.87–1.07	0.513	0.797	0.98	0.87–1.10	0.754	0.825
1-year pre-HD SNa	0.91	0.79–1.04	0.160	0.559	0.87	0.75–0.99	0.041	0.810	0.89	0.77–1.03	0.120	0.813
2-year pre-HD SNa	0.88	0.77–1.01	0.069	0.591	0.84	0.73–0.97	0.019	0.807	0.86	0.74–0.99	0.042	0.818
3-year pre-HD SNa	0.90	0.78–1.04	0.159	0.572	0.85	0.73–0.99	0.032	0.804	0.87	0.74–1.02	0.085	0.825
CCVE
Baseline pre-HD SNa	0.96	0.86–1.07	0.456	0.531	0.90	0.79–1.02	0.088	0.757	0.90	0.79–1.03	0.124	0.805
1-year pre-HD SNa	0.90	0.79–1.04	0.154	0.571	0.85	0.74–0.98	0.020	0.774	0.83	0.72–0.96	0.011	0.796
2-year pre-HD SNa	0.88	0.77–1.01	0.080	0.615	0.85	0.75–0.97	0.017	0.781	0.83	0.73–0.96	0.010	0.824
3-year pre-HD SNa	0.88	0.76–1.01	0.072	0.616	0.83	0.72–0.96	0.010	0.786	0.83	0.72–0.96	0.012	0.829

Model 1 was adjusted for age, body mass index, and CCVD history.

Model 2 was adjusted for Model 1 variables + albumin (for all-cause mortality) or C-reactive protein and ferritin (for CCVE).

Table 4. Cox proportional hazards models of ΔSNa for all-cause mortality and cardio-cerebrovascular event.

		Unadjusted				Model 1				Model 2				Model3
	HR	95% CI	P	AUC	HR	95% CI	P	AUC	HR	95% CI	P	AUC	HR	95% CI	P	AUC
All-cause Mortality
Baseline ΔSNa	1.03	0.92–1.16	0.560	0.529	1.08	0.96–1.21	0.196	0.800	1.07	0.95–1.21	0.266	0.825	1.13	0.94–1.36	0.206	0.802
1-year ΔSNa	1.09	0.92–1.28	0.341	0.554	1.13	0.96–1.34	0.141	0.803	1.11	0.94–1.32	0.217	0.815	0.99	0.76–1.28	0.919	0.809
2-year ΔSNa	1.20	1.00–1.44	0.049	0.609	1.22	1.01–1.48	0.042	0.806	1.23	1.00–1.50	0.045	0.820	1.06	0.78–1.44	0.711	0.808
3-year ΔSNa	1.22	1.01–1.47	0.040	0.620	1.26	1.03–1.55	0.026	0.809	1.24	1.00–1.53	0.046	0.828	1.16	0.85–1.6	0.346	0.806
CCVE
Baseline ΔSNa	1.04	0.92–1.18	0.526	0.515	1.12	0.98–1.27	0.091	0.748	1.13	0.99–1.28	0.076	0.801	1.07	0.9–1.27	0.456	0.753
1-year ΔSNa	1.21	1.02–1.44	0.030	0.613	1.32	1.11–1.57	0.002	0.787	1.31	1.10–1.55	0.002	0.815	1.31	1–1.7	0.047	0.786
2-year ΔSNa	1.34	1.11–1.61	0.002	0.703	1.41	1.16–1.71	0.001	0.817	1.45	1.18–1.78	<0.001	0.842	1.54	1.12–2.14	0.009	0.818
3-year ΔSNa	1.40	1.16–1.70	0.001	0.722	1.53	1.24–1.89	<0.001	0.827	1.51	1.21–1.88	<0.001	0.846	1.75	1.25–2.45	0.001	0.829

Model 1 was adjusted for age, body mass index, and CCVD history.

Model 2 was adjusted for Model 1 variables + albumin (for all-cause mortality) or C-reactive protein and ferritin (for CCVE).

Model 3 was adjusted for Model 1 variables + pre-HD SNa.

Table 5. Adjusted hazard ratio associated with stratification by pre-HD SNa and ΔSNa.

	Pre-HD SNa < 138				Pre-HD SNa ≥ 138
Duration	ΔSNa < −1 HR (95% CI)	p	ΔSNa ≥ −1 HR (95% CI)	p	ΔSNa < −1 HR (95% CI)	p	ΔSNa ≥ −1 HR (95% CI)	p
All-cause Mortality
Baseline	1.74 (0.20–15.32)	0.617	1.21 (0.49–2.97)	0.680	1 (reference)	NA	2.52 (0.99–6.38)	0.052
1-year	0.42 (0.08–2.13)	0.293	2.35 (1.02–5.44)	0.045	1 (reference)	NA	1.50 (0.46–4.87)	0.502
2-year	0.82 (0.19–3.58)	0.797	1.90 (0.79–4.60)	0.152	1 (reference)	NA	1.77 (0.65–4.79)	0.260
3-year	0.53 (0.11–2.62)	0.440	2.07 (0.82–5.19)	0.122	1 (reference)	NA	1.91 (0.70–5.21)	0.205
CCVE
Baseline	1.27 (0.15–10.70)	0.824	1.88 (0.74–4.79)	0.185	1 (reference)	NA	1.21 (0.42–3.47)	0.719
1-year	1.56 (0.17–14.22)	0.693	4.91 (1.95–12.33)	0.001	1 (reference)	NA	4.33 (1.39–13.47)	0.011
2-year	1.44 (0.14–14.24)	0.757	7.12 (2.27–22.32)	0.001	1 (reference)	NA	3.90 (1.18–12.96)	0.026
3-year	1.18 (0.13–10.68)	0.884	9.78 (2.9–32.95)	<0.001	1 (reference)	NA	7.96 (2.35–26.91)	0.001

Model was adjusted for age, body mass index, and CCVD history + albumin (for all-cause mortality) or C-reactive protein and ferritin (for CCVE).

Figure 1. Multivariable-adjusted restricted cubic spline plots of pre-HD SNa for (A) all-cause mortality, with adjustment of age, BMI, CCVD history, SCr, and Alb; and for (B) cardio-cerebrovascular event, with adjustment of age, BMI, CCVD history, CRP and Ferr. Grey, blue, orange and red color represent the RCS curves of baseline pre-HD SNa, 1-year pre-HD SNa, 2-year pre-HD SNa and 3-year pre-HD SNa, respectively. Shadow represents the 95% confident interval.

Figure 2. Multi-variable restricted cubic spline plots of ΔSNa for (A) all-cause mortality with adjustment of age, BMI, CCVD history, SCr, and Alb; and for (B) cardio-cerebrovascular event, with adjustment of age, BMI, CCVD history, CRP and Ferr. Grey, blue, orange and red color represent the RCS curves of baseline ΔSNa, 1-year ΔSNa, 2-year ΔSNa and 3-year ΔSNa. Shadow represents the 95% confidence interval.

Figure 3. Kaplan-Meier plots stratified by 3-year average pre-HD SNa and ΔSNa for (A) all-cause mortality and (B) cardio-cerebrovascular event. Significance was examined by Log-rank test.