Differences in Bio-incompatibility among Four Biocompatible Dialyzer Membranes Using in Maintenance Hemodialysis Patients

Figures & data

Table 1. Dialyzer characteristics.

Dialyzer	Membrane	Membrane area (m^2)	Sterilization	Kuf (mL × min^−1 × mmHg^−1)	KoA
F7	PS	1.6	Steam	6.4	787
130-DS	PES	1.3	γ-ray	36.0	729
130U	CTA	1.3	γ-ray	25.8	1003
B3-1.6A	PMMA	1.6	γ-ray	8.7	736

Note: PS, polysulfone; PES, ployethersulfone; CTA, cellulose triacetate; PMMA, polymethylmethacrylate; Kuf, ultrafiltration ratio of dialyzers; KoA, mass transfer area coefficient.

Table 2. Patients’ characteristics on month 0.

Groups^a	PES	CTA	PMMA
N	20	20	20
Male/female	10/10	10/10	10/10
Age (year)	53.8 ± 12.1	56.1 ± 13.5	50.1 ± 8.8
Time on HD (year)	8.25 ± 2.56	9.00 ± 3.34	8.37 ± 3.98
Protopathy [n, (%)]
Chronic glomerulonephritis	18 (90%)	16 (80%)	16 (80%)
Diabetes	1 (5%)	1 (5%)	1 (5%)
Hypertension	1 (5%)	1 (5%)	2 (10%)
ADPKD	0 (0%)	2 (10%)	1 (5%)
SBPpre-HD (mmHg)	119.8 ± 22.6	120.4 ± 12.8	129.7 ± 21.9
DBPpre-HD (mmHg)	70.3 ± 12.3	68.6 ± 17.8	76.4 ± 15.0
SBPpost-HD (mmHg)	106.5 ± 31.2	102.7 ± 18.2	113.8 ± 13.1
DBPpost-HD (mmHg)	66.5 ± 19.8	67.1 ± 17.0	74.3 ± 14.2
Dry weight (kg)	60.9 ± 10.1	64.2 ± 10.1	67.2 ± 14.3
Ultrafiltration volume (mL)	3,78 ± 1.09	3.41 ± 0.78	3.71 ± 0.82
Urea reduction ratio (%)	73.86 ± 6.86	71.99 ± 6.50	70.59 ± 7.33
Hemoglobin (g/L)	111.9 ± 13.2	112.9 ± 19.4	111.2 ± 18.1
Creatinine (μmol/L)	912.5 ± 178.9	871.8 ± 209.3	898.5 ± 199.8
Urea (mmol/L)	24.0 ± 5.5	22.1 ± 4.1	23.8 ± 5.0
Uric acid (mmol/L)	389.9 ± 61.3	368.8 ± 51.5	405.3 ± 77.3
Albumin (g/L)	38.2±2.4	38.8 ± 2.9	40.5 ± 2.2
Total cholesterol (mmol/L)	4.97 ± 1.46	4.92 ± 0.72	4.71 ± 1.22
Triglyceride (mmol/L)	2.33 ± 1.20	2.33 ± 1.98	2.62 ± 2.03
Calcium (mmol/L)	2.30 ± 0.16	2.30 ± 0.29	2.30 ± 0.22
Phosphorus (mmol/L)	1.93 ± 0.57	1.93 ± 0.41	2.01 ± 0.43
Ferritin (ng/mL)	310.2 ± 228.2	372.1 ± 205.9	287.2 ± 114.2
β2-microglobulin	27.53 ± 7.44	25.65 ± 6.65	25.01 ± 6.10
Intact parathyroid hormone (pg/mL)	336.1 ± 446.4	378.2 ± 361.7	270.0 ± 221.0
hs-CRP (mg/L)	0.58 ± 0.29	0.59 ± 0.42	0.78 ± 0.59

Notes: SBP_pre-HD, systolic blood pressure pre-hemodialysis; DBP_pre-HD, diastolic blood pressure pre-hemodialysis; SBP_post-HD, systolic blood pressure post-hemodialysis; DBP_post-HD, diastolic blood pressure post-hemodialysis; ADPKD, autosomal dominant polycystic kidney disease. There were no statistical significant differences among three different groups on all above variables (p > 0.05).

^aOn month 0, 60 maintenance hemodialysis patients using polysulfone (PS) membrane dialyzers were divided into three different groups according to three different dialyzers: PES, ployethersulfone; CTA, cellulose triacetate; PMMA, polymethylmethacrylate.

Table 3. Reduction ratios (%) of several solutes among different groups.

Solutes	Time	Group PES (N = 20)	Group CTA (N = 20)	Group PMMA (N = 20)
Urea	Month 0	73.65 ± 6.82	72.03 ± 6.56	70.65 ± 7.34
	Month 3	71.74 ± 8.04	70.96 ± 6.88	68.91 ± 6.19
	Month 6	71.36 ± 6.89	72.38 ± 5.45	69.88 ± 5.04
Creatinine	Month 0	64.53 ± 6.96	63.13 ± 7.20	63.13 ± 6.15
	Month 3	63.57 ± 8.02	64.22 ± 8.69	61.22 ± 5.42
	Month 6	61.35 ± 6.21	63.16 ± 4.67	62.28 ± 5.30
Uric acid	Month 0	74.70 ± 6.79	75.27 ± 6.40	72.04 ± 6.64
	Month 3	74.07 ± 7.42	74.82 ± 5.06	71.24 ± 5.98
	Month 6	73.31 ± 8.74	75.10 ± 7.48	71.28 ± 4.81
β2-microglobulin	Month 0	26.72 ± 25.71	12.50 ± 28.65	19.20 ± 16.23
	Month 3	10.18 ± 16.25	15.06 ± 21.60	16.44 ± 26.18
	Month 6^**	15.05 ± 12.56	12.43 ± 14.99	23.65 ± 22.11
ADMA^**	Month 0	23.48 ± 13.00	25.74 ± 9.30	26.84 ± 14.09
	Month 3	24.99 ± 19.79	22.45 ± 18.33	27.26 ± 15.75
	Month 6	27.04 ± 12.16	22.94 ± 10.21	27.22 ± 12.01

Notes: There were no statistical significant differences among three different groups on all above variables at different time points by using q-test (p > 0.05). However, the differences were statistically significant in group PES when the reduction ratios of β₂-microglobulin are compared by using paired-sample t-tests, month 0 versus month 3. There were no significant differences in paired-sample t-tests on other parameters among month 0 versus month 3, month 0 versus month 6, and month 3 versus month 6 (p > 0.05).

*Denotes p = 0.023, and month 0 versus month 6.

^**Denotes p = 0.056

Table 4. Blood levels of inflammation factors.

Inflammation factors	Time		PES group (N = 20)	CTA group (N = 20)	PMMA group (N = 20)
hs-CRP (mg/L)	Month 0	Pre-HD	0.58 ± 0.29	0.59 ± 0.42	0.78 ± 0.59
		Post-HD	0.46 ± 0.26	0.60 ± 0.36	0.52 ± 0.19
	Month 3	Pre-HD	0.72 ± 0.37	0.64 ± 0.48	0.56 ± 0.23
		Post-HD	0.59 ± 0.30	0.47 ± 0.24	0.53 ± 0.27
	Month 6	Pre-HD	0.60 ± 0.30	0.61 ± 0.29	0.49 ± 0.22
		Post-HD	0.48 ± 0.20	0.56 ± 0.32	0.54 ± 0.44
IL-1β (pg/mL)	Month 0	Pre-HD	42.74 ± 14.21	42.84 ± 13.76	37.51 ± 10.22
		Post-HD	35.64 ± 12.14	34.63 ± 14.08	31.33 ± 12.04
	Month 3	Pre-HD	40.12 ± 23.78	36.63 ± 13.85	36.36 ± 19.91
		Post-HD	31.26 ± 9.09	29.39 ± 12.88	32.35 ± 14.05
	Month 6	Pre-HD	33.56 ± 18.32	38.20 ± 19.50	37.27 ± 19.47
		Post-HD	30.91 ± 11.48	29.34 ± 20.87	28.40 ± 13.96
IL-13 (pg/mL)	Month 0	Pre-HD	38.06 ± 13.92	38.17 ± 15.60	32.71 ± 9.84
		Post-HD	40.95 ± 12.25	36.98 ± 10.88	34.98 ± 14.07
	Month 3	Pre-HD	39.17 ± 14.94	40.44 ± 12.25	39.55 ± 13.47
		Post-HD	42.99 ± 17.42	40.70 ± 18.94	38.58 ± 12.41
	Month 6	Pre-HD	37.29 ± 16.76	39.44 ± 12.74	36.77 ± 12.83
		Post-HD	40.54 ± 8.86	42.96 ± 17.83	36.51 ± 16.59

Notes: There were no statistical significant differences among three different groups on all above variables at different time points by using q-test (p > 0.05). When paired-sample t-tests were used to compare the differences on blood levels of inflammation factors between pre- and post-hemodialysis (HD), and on all parameters among month 0 versus month 3, month 0 versus month 6, and month 3 versus month 6, the significant differences were not found (p > 0.05).

Table 5. Blood levels of complements.

Complement		Time point	Group PES (N = 20)	Group CTA (N = 20)	Group PMMA (N = 20)	Within-subjects effects	Within-subjects effects	Between-subjects effects
						Minute	Group × minute	Group
C3a (ng/mL)	Month 0	0 min	117.42 ± 27.40	120.84 ± 30.01	117.92 ± 35.99	p = 0.001	p = 0.768	p = 0.444
		15 min	146.19 ± 48.31	168.20 ± 56.01	183.09 ± 57.02
		240 min	137.68 ± 49.91	149.45 ± 44.71	135.20 ± 43.08
	Month 3	0 min	108.14 ± 26.65	110.27 ± 21.24	96.11 ± 30.84	p < 0.001	p = 0.622	p = 0.098
		15 min	172.48 ± 50.20	154.49 ± 48.56	141.48 ± 50.70
		240 min	131.81 ± 43.51	132.29 ± 36.52	115.38 ± 37.49
	Month 6	0 min	96.88 ± 31.57	97.80 ± 27.45	85.05 ± 17.28	p < 0.001	p = 0.675	p = 0.376
		15 min	164.53 ± 37.62	155.89 ± 36.73	146.31 ± 41.07
		240 min	120.39 ± 36.78	115.99 ± 27.70	116.69 ± 32.95
Within-subjects effects	Minute	p < 0.001	p < 0.001	p < 0.001
Within-subjects effects	Month × minute	p = 0.954	P = 0.633	p = 0.483
Between-subjects effects	Month	p = 0.571	p = 0.058	p = 0.004^a
C5a (ng/mL)	Month 0	0 min	76.28 ± 15.55	76.47 ± 19.66	75.57 ± 20.27	p = 0.646	p = 0.773	p = 0.675
		15 min	85.21 ± 21.13	80.27 ± 23.17	84.49 ± 23.58
		240 min	82.50 ± 31.30	76.20 ± 17.83	75.51 ± 19.25
	Month 3	0 min	74.70 ± 18.70	87.16 ± 30.60	60.59 ± 19.07	p = 0.001	p = 0.324	p = 0.023^b
		15 min	98.85 ± 27.78	91.77 ± 26.11	85.30 ± 23.50
		240 min	83.96 ± 27.87	80.46 ± 30.94	72.74 ± 28.97
	Month 6	0 min	77.45 ± 20.86	89.56 ± 32.89	67.88 ± 17.87	p < 0.001	p = 0.561	p = 0.092
		15 min	103.5 ± 27.92	101.77 ± 28.63	94.61 ± 25.97
		240 min	93.02 ± 31.01	89.08 ± 34.30	81.72 ± 15.17
Within-subjects effects	Minute	p < 0.001	p = 0.043	p < 0.001
Within-subjects effects	Month × minute	p = 0.526	p = 0.887	p = 0.444
Between-subjects effects	Month	p = 0.118	p = 0.051	p = 0.415

Notes: Statistical method of repeated measures was used to compare the blood levels of C3a and C5a among different time points and different groups, respectively. In a certain group, the blood levels of C3a and C5a were significantly different among 0, 15, and 240 min (p < 0.05). There were no significant differences on the levels of C3a and C5a among different months both in group PES and in group CTA (p > 0.05).

^aIn group PMMA, there were significant differences on the C3a levels rather than C5a levels among month 0, month 3, and month 6 (C3a, p = 0.004, C5a, p > 0.05). Moreover, multiple comparisons on C3a levels in group PMMA show significant differences on month 0 versus month 3 (p = 0.015) and month 0 versus month 6 (p = 0.009), and no significant differences between month 3 and month 6 (p = 1.000). (These results were not listed in Table 5.) For blood C3a levels, the significant differences appear among 0, 15, and 240 min in every month (p < 0.001). There were no significant differences on C3a levels on a certain month among group PES, group CTA, and group PMMA (p > 0.05). For blood C5a levels, the differences were not significant on month 0 both among three time points and among three groups (p > 0.05). However, there were significant differences among 0, 15, and 240 min, both on month 3 and month 6 (p < 0.001).

^bFurthermore, the C5a levels on month 3 were significantly different among three groups (p = 0.023). By multiple comparisons, there were significant differences between group PES and PMMA (p = 0.023), and the differences were not significant in both group PES versus group CTA and group CTA versus PMMA (p > 0.05). (These results were not listed in Table 5.)

Figure 1. Changes of blood levels on complement (C3a) (A); on complement (C5a) (B). The maintenance hemodialysis patients all were treated by polysulfone membrane dialyzers on month 0. They were divided into three different groups randomly equally according to different membranes as group PES, group CTA, and group PMMA. PES, ployethersulfone; CTA, cellulose triacetate; PMMA, polymethylmethacrylate. The number of patients in each group was 20. The patients were followed-up for 6 months. The blood levels of complement 3a (C3a) and 5a (C5a) were detected on months 0, 3, and 6. They were detected at 0, 15, and 240 min in one session on each month. The details of data are listed in Table 5.

Notes: Blood levels of both C3a and C5a increased significantly at 15 min and decreased gradually at 240 min in most sessions, except for C5a levels on month 0. The pattern on changes of C3a and C5a in three groups was similar.

*Denotes However, the range of C3a levels in group PMMA were declined significantly when the dialyzers changed from PS to PMMA membrane, both on month 3 and on month 6 (p < 0.05).

^**Denotes The changes of C5a levels were significantly different between group CTA and PMMA on month 3 (p < 0.05).

Table 6. Blood cells’ detection.

Blood cells	Time		PES group (N = 20)	CTA group (N = 20)	PMMA group (N = 20)
White blood cell (×10^9/L)	Month 0	0 min	5.15 ± 1.62	5.72 ± 1.58	5.60 ± 1.42
		15 min	4.50 ± 1.74	4.57 ± 1.13	4.44 ± 0.98
		30 min	5.22 ± 1.74	5.19 ± 1.16	5.64 ± 1.22
		60 min	5.74 ± 1.55	5.85 ± 1.14	5.97 ± 0.82
		240 min	5.74 ± 1.55	6.46 ± 1.53	7.41 ± 1.87
	Month 3	0 min	4.99 ± 1.75	5.58 ± 1.47	6.02 ± 1.36^a
		15 min	4.57 ± 1.45	4.77 ± 2.01	2.32 ± 1.11^b
		30 min	5.04 ± 1.62	5.07 ± 1.09	5.39 ± 2.38
		60 min	5.28 ± 1.71	5.67 ± 1.33	6.36 ± 2.55
		240 min	5.67 ± 1.80	6.03 ± 1.65	7.53 ± 2.31
	Month 6	0 min	5.28 ± 1.54	5.22 ± 0.93	6.45 ± 1.29^c
		15 min	4.67 ± 1.44	4.06 ± 0.93	2.20 ± 1.42^d
		30 min	5.17 ± 1.56	5.02 ± 0.96	4.74 ± 1.35^e
		60 min	5.15 ± 1.64	5.52 ± 1.30	6.82 ± 1.58^f
		240 min	5.49 ± 2.02	5.84 ± 1.38	8.44 ± 1.61^g,h
Red blood cell (×10^12/L)	Month 0	0 min	3.70 ± 0.64	3.76 ± 0.80	3.62 ± 0.52
		15 min	3.58 ± 0.67	3.72 ± 0.78	3.58 ± 0.51
		30 min	3.60 ± 0.67	3.67 ± 0.79	3.63 ± 0.51
		60 min	3.66 ± 0.73	3.79 ± 0.68	3.68 ± 0.53
		240 min	4.23 ± 0.92	4.34 ± 0.83	4.13 ± 0.58
	Month 3	0 min	3.66 ± 0.67	3.68 ± 0.88	3.61 ± 0.65
		15 min	3.58 ± 0.66	3.71 ± 0.90	3.58 ± 0.57
		30 min	3.59 ± 0.69	3.68 ± 0.92	3.67 ± 0.58
		60 min	3.73 ± 0.76	3.77 ± 0.92	3.73 ± 0.59
		240 min	4.16 ± 0.94	4.15 ± 0.97	4.12 ± 0.66
	Month 6	0 min	3.78 ± 0.66	3.79 ± 0.71	3.62 ± 0.61
		15 min	3.64 ± 0.66	3.74 ± 0.74	3.51 ± 0.45
		30 min	3.64 ± 0.63	3.81 ± 0.73	3.58 ± 0.49
		60 min	3.97 ± 1.08	3.86 ± 0.74	3.57 ± 0.55
		240 min	4.26 ± 0.86	4.32 ± 0.84	4.12 ± 0.60
Platelet (×10^9/L)	Month 0	0 min	164.90 ± 54.04	160.18 ± 50.69	156.05 ± 56.39
		15 min	162.39 ± 51.74	152.12 ± 48.79	153.53 ± 56.75
		30 min	161.50 ± 53.34	152.59 ± 43.48	152.89 ± 52.84
		60 min	167.39 ± 57.52	155.59 ± 47.83	156.95 ± 55.06
		240 min	191.33 ± 67.61	177.35 ± 53.08	186.58 ± 60.22
	Month 3	0 min	159.90 ± 53.67	163.11 ± 56.29	160.05 ± 62.45
		15 min	162.78 ± 57.51	155.71 ± 49.03	146.21 ± 59.13
		30 min	165.61 ± 61.39	157.24 ± 51.82	148.63 ± 58.72
		60 min	172.94 ± 69.84	160.94 ± 55.72	149.16 ± 56.52
		240 min	197.83 ± 76.69	178.94 ± 58.08	168.53 ± 61.80
	Month 6	0 min	161.14 ± 53.24	159.72 ± 43.33	151.11 ± 57.56
		15 min	165.33 ± 53.40	153.94 ± 46.04	146.42 ± 51.90
		30 min	167.72 ± 54.06	158.82 ± 48.82	147.95 ± 52.62
		60 min	175.93 ± 58.13	160.53 ± 46.98	152.37 ± 53.21
		240 min	196.61 ± 66.88	174.88 ± 50.87	172.74 ± 57.43

Notes: There were no statistically significant differences among three different groups on all above variables at different time points by using q-test (p > 0.05). There were no statistical differences on other parameters by using paired-sample t-tests among month 0 versus month 3, month 0 versus month 6, and month 3 versus month 6 (p > 0.05), except the white blood cell (WBC) count in group PMMA. When paired-sample t-tests were used to compare the differences on the WBC count, there were significant differences among month 0 versus month 3 at ^a0 min (p = 0.042) and ^b15 min (p < 0.01), month 0 versus month 6 in ^c-g0–240 min (0 min, p = 0.01; 15 min, p < 0.01; 30 min, p = 0.026; 60 min, p = 0.39; 240 min, p = 0.001), and month 3 versus month 6 at ^h240 min (p = 0.004) in group PMMA.

Figure 2. Blood cell detection of (A) white blood cell count; (B) red blood cell count; (C) hemoglobin; (D) hematocrit; (E) platelet count.The maintenance hemodialysis patients all were treated by polysulfone membrane dialyzers on month 0. They were divided into three different groups randomly according to different membranes as group PES, group CTA, and group PMMA. PES, ployethersulfone; CTA, cellulose triacetate; PMMA, polymethylmethacrylate. The number of patients in each group was 20. The patients were followed-up for 6 months. White blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (Hb), hematocrit (Hct), platelet counts (PLT) in peripheral circulation were detected on months 0, 3, and 6. The above parameters were detected at 0, 15, 30, 60, and 240 min in one session on each month. The WBC decreased significantly at 15 min and increased gradually at 30, 60, 240 min in each session. The pattern on changes of WBC in three groups was similar. Notes: *However, the WBC declined much significantly at 15 min and raised up much more quickly at 30, 60, 240 min when the patients were treated by using PMMA membrane than other membranes (p < 0.05). The other parameters also first decreased at 15 min, and then increased gradually during residual period in one dialysis session. There were no statistical differences in RBC, Hb, Hct, and PLT neither among each group nor among the months 0, 3, and 6 (p > 0.05).

Table 7. Comparison of solute removal markers and biocompatible markers among four groups.

	PS	PES	CTA	PMMA
Solute removal markers
RRUrea (%)	NS	NS	NS	NS
RRβ2-microglobulin (%)	NS	↓^a	NS	NS
RRADMA (%)	NS	NS	NS	NS
Biocompatible markers
WBC (×10^9/L)	NS	NS	NS	↓^a
ΔC3a (ng/mL)	NS	NS	NS	↓^a
C5a (ng/mL)	NS	NS	NS	↓^b
hs-CRP (mg/L)	NS	NS	NS	NS
IL-1β (pg/mL)	NS	NS	NS	NS
IL-13 (pg/mL)	NS	NS	NS	NS

Notes: RR, reduction ratio; NS, there were no significant differences when one group is compared with other groups.

^aIt was decreased for certain markers when they compared to PS membrane (baseline level). When PS membrane dialyzer transferred to PES, reduction ratio of β2-microglobulin decreased significantly. When PS membrane dialyzer transferred to PMMA, the white blood cell counts declined more deeply and the blood complement levels of C3a increased more gently at 15 min.

^bThe blood complement levels of C5a at time point on month 3 were decreased significantly in PMMA group compared with other two groups (PES and CTA).