Impact of cytokine genotype on cardiovascular surrogate markers in hemodialysis patients

Figures & data

TABLE 1. Baseline characteristics of the study population (102 chronic HD patients)

Age (years)	47.0 ± 13.9
Male gender %	62
Duration of dialysis (months)	62 ± 22
Body mass index (kg/m²)	22.6 ± 3.8
Smoking (%)	22.1
Interdialytic weight gain (kg)	3.0 ± 1.2
Primary diseases (n)
Chronic glomerulonephritis	55
Nephrosclerosis	18
Pyelonephritis	8
Amyloidosis	6
Polycystic kidney disease	4
Other disease/unknown	11
Anti-hypertensive agent (n)
ACE inhibitor	4
Angiotensin receptor blocker	3
Ca channel blocker	6
β-Blocker	2
Patients treated with statin (n)	4
Ambulatory systolic BP (mmHg)	127 ± 21
Ambulatory diastolic BP (mmHg)	80 ± 15
Albumin (g/dL)	3.6 ± 0.4
Hemoglobulin (g/L)	10.3 ± 1.6
Total cholesterol (mg/dL)	155 ± 40
LDL cholesterol (mg/dL)	88 ± 30
HDL cholesterol (mg/dL)	38 ± 11
Triglycerides (mg/dL)	146 ± 67
Equilibrated Kt/V	1,4 ± 0.2
Erythrocyte sedimentation rate (mm/h)	13 ± 12
PTH level (pg/L)	237
Ca (mg/dL)	8.1 ± 2.4
P (mg/dL)	5.2 ± 2.1
C-reactive protein (mg/dL)	0.49 ± 0.51

TABLE 2. Genotype distribution of the study population

	Number	Genotype	Phenotype/cytokine production
IL-10 –1082	102	AA 28 (27%)	High (GG) 34 (33%)
		AG 40 (40%)	Low (AA + AG) 68(67%)
		GG 34 (33%)
IL-10 –819	102	CC 52 (51%)	High (CC) 52 (51%)
		CT 36 (36%)	Low (CT + TT) 48 (49%)
		TT 12 (13%)
IL-10 –592	102	AA 26 (26%)	High (CC) 44 (43%)
		AC 32 (31%)
		CC 44 (43%)	Low (AA + AC) 58 (57%)
TNF-α −308	101	AA 5 (5%)	High (AA + AG) 33 (33%)
			Low (GG) 68 (67%)
TNF-α −238	101	AA 2 (1%)	High (AA + AG) 18 (17%)
		AG 16 (16%)
		GG 84 (83%)	Low (GG) 84 (83%)
		AG 28 (28%)
		GG 68 (67%)

TABLE 3. Baseline demographic and laboratory parameters (mean ± SD) according to cytokine genotype in study population

Parameters	IL-10 –1082 A/G		TNF-alpha –308 A/G
	High producer (n = 34)	Low producer (n = 68)	High producer (n = 33)	Low producer (n = 68)
Age (years)	47.8 ± 14.6	48.0 ± 13.7	48.5 ± 13.8	45.5 ± 17.6
Male/female (n)	24/16	47/34	28/12	56/24
BMI (kg/m^2)	22.6 ± 2.6	22.3 ± 3.8	22.6 ± 3.6	21.4 ± 3.8
Smoking (%)	22.9	22.2	23.5	26.4
Hemodialysis duration (months)	72.0 ± 39.3	72.7 ± 58.6	72.5 ± 64.2	76.0 ± 54.2
Antihypertensive (n)
ACE inhibitor	2	2	2	2
ARB	2	1	1	2
Ca channel antagonist	2	4	3	3
β-Blocker	1	1	1	1
Statin medication (n)	2	2	1	3
Hemoglobin (g/dL) (Baseline)	10.5 ± 1.6	10.9 ± 1.7	10.2 ± 1.6	10.9 ± 1.8
SBP (mmHg) (Baseline)	130 ± 6	127 ± 22	131 ± 23	134 ± 22
DBP (mmHg) (Baseline)	79 ± 14.3	82 ± 16	81 ± 16	82 ± 11
Total cholesterol (mg/dL) (Baseline)	148 ± 42	159 ± 36	162 ± 39	143 ± 39
LDL cholesterol (mg/dL) (Baseline)	81 ± 33	91 ± 29	93 ± 31	85 ± 34
Triglycerides (mg/dL)	153 ± 88	149 ± 85	158 ± 105	144 ± 83
HDL cholesterol (mg/dL)	37 ± 14	38 ± 13	37 ± 14	38 ± 13
Albumin (g/dL)	3.8 ± 0.3	3.7 ± 0.4	3.8 ± 0.5	3.9 ± 0.4
ESR (mm/h)	11 ± 9	11 ± 8	11 ± 10	11 ± 8
iPTH (pg/L)	221 ± 293	207 ± 223	297 ± 378	297 ± 378
Ca (mg/dL)	8.7 ± 2.7	8.4 ± 2.6	8.1 ± 2.3	8.8 ± 1.6
P (mg/dL)	4.9 ± 2.4	5.2 ± 2.1	5.0 ± 2.1	4.9 ± 2.2
Kt/V	1.4 ± 0.3	1.3 ± 0.2	1.3 ± 0.3	1.4 ± 0.4
Interdialytic weight gain (kg)	2.7 ± 1.2	2.9 ± 1.3	3.0 ± 1.2	2.8 ± 1.2

TABLE 4. Average parameters (mean ± SD) according to cytokine genotype during study period

Parameters	IL-10 –1082 A/G		TNF-alpha –308 A/G
	High producer (n = 31)	Low producer (n = 61)	High producer (n = 30)	Low producer (n = 6)2
Hemoglobin (g/dL)	10.3 ± 1.6	10.6 ± 1.5	10.2 ± 1.7	10.8 ± 1.7
Mean EPO doses (unit/month)
EPO alpha	15,480	15,737	16,000	15,483
EPO beta	19,350	24,590	20,000	21,290
SBP (mmHg)	132 ± 27	133 ± 23	129 ± 22	130 ± 16
DBP (mmHg)	81 ± 21	81 ± 13	82 ± 16	79 ± 14
Total cholesterol (mg/dL)	151 ± 42	158 ± 41	158 ± 43	153 ± 41
LDL cholesterol (mg/dL)	89 ± 34	90 ± 31	95 ± 32	89 ± 35
Triglycerides (mg/dL)	158 ± 84	159 ± 86	160 ± 105	148 ± 105
HDL cholesterol (mg/dL)	36 ± 11	37 ± 14	39 ± 15	37 ± 12
Albumin (g/dL)	3.8 ± 0.4	3.6 ± 0.4	3.6 ± 0.5	3.7 ± 0.4
ESR (mm/h)	13 ± 7	12 ± 9	13 ± 9	11 ± 9
iPTH (pg/L)	241 ± 244	237 ± 256	260 ± 352	218 ± 360
Ca (mg/dL)	8.7 ± 1.9	8.4 ± 2.0	8.1 ± 2.2	8.1 ± 2.3
P (mg/dL)	5.1 ± 2.4	5.3 ± 2.2	4.9 ± 2.2	5.0 ± 2.2
Kt/V	1.3 ± 0.2	1.4 ± 0.2	1.3 ± 0.4	1.4 ± 0.2
Interdialytic weight gain (kg)	2.9 ± 1.3	2.8 ± 1.2	2.9 ± 1.3	2.9 ± 1.4

FIGURE 1. Annual CIMT and LVMI progression due to TNF-α −308 A/G gene polymorphism.

FIGURE 2. Annual LVMI and CIMT progression due to combination of TNF-α −308/IL-10 −1082 gene polymorphisms.

TABLE 5. LVMI and CIMT measurements in cytokine genotype groups

Parameters	All patients	IL-10 –1082 A/G		TNF-alpha –308 A/G
		High producer (n = 31)	Low producer (n = 61)	High producer (n = 30)	Low producer (n = 62)
LVMI (g/m^2) (Baseline)	106 ± 32	99 ± 32	109 ± 32	107 ± 30	105 ± 33
LVMI (g/m^2) (1 year)	109 ± 34	103 ± 33	112 ± 35	113 ± 33	108 ± 34
LVMI (g/m^2) (2 year)	113 ± 34	107 ± 33	117 ± 35	118 ± 33	111 ± 35
CIMT (mm) (Baseline)	0.67 ± 0.15	0.63 ± 0.14	0.69 ± 0.18	0.67 ± 0.14	0.66 ± 0.15
CIMT m(m) (1 year)	0.69 ± 0.16	0.66 ± 0.14	0.72 ± 0.16	0.72 ± 0.16	0.68 ± 0.16
CIMT (mm) (2 year)	0.72 ± 0.16	0.68 ± 0.15	0.76 ± 0.16	0.75 ± 0.17	0.71 ± 0.17

TABLE 6. LVMI and CIMT measurements in cytokine genotype combination groups

Parameters	High TNF-alpha/high IL-10 (n = 5)	High TNF-alpha/low IL-10 (n = 22)	Low TNF-alpha/high IL-10 (n = 28)	Low TNF-alpha /low IL-10 (n = 37)
LVMI (g/m^2) (Baseline)	97 ± 16	108 ± 32	101 ± 34	109 ± 32
LVMI (g/m^2) (1 year)	104 ± 18	112 ± 36	105 ± 34	111 ± 35
LVMI (gr/m^2) (2 year)	108 ± 20	116 ± 36	108 ± 34	115 ± 35
CIMT (mm) (Baseline)	0.68 ± 0.14	0.66 ± 0.15	0.65 ± 0.16	0.68 ± 0.15
CIMT (mm) (1 year)	0.69 ± 0.16	0.71 ± 0.18	0.67 ± 0.15	0.70 ± 0.16
CIMT (mm) (2 year)	0.71 ± 0.15	0.74 ± 0.19	0.69 ± 0.16	0.73 ± 0.15

FIGURE 3. CRP Levels due to TNF-α −308 A/G Gene polymorphism.

FIGURE 4. CRP levels due to combination of TNF-α −308/IL-10 −1082 gene polymorphisms.