The relationship between calcification inhibitor levels in chronic kidney disease and the development of atherosclerosis

Figures & data

Table 1. Comparison of the demographic, clinical and laboratory data of the healthy control group and the CKD group.

Parameters	Healthy control group (n = 32)	CKD group (n = 92)	p
Age (years)	46.2 ± 10.4	46.8 ± 10.3	NS
Gender (female %)	%53	%53	NS
BMI (kg/m^2)	25.9 ± 4.0	26.3 ± 3.7	NS
SBP (mmHg)	118 ± 9	131 ± 16	<0.0001
DBP (mmHg)	75 ± 6	84 ± 12	<0.0001
FPG (mg/dl)	83 ± 11	88 ± 9	0.0344
Urea (mg/dl)	29.2 ± 8.5	68.9 ± 35.2	<0.0001
Creatinine (mg/dl)	0.7 ± 0.2	2.3 ± 1.4	<0.0001
Uric Acid (mg/dl)	4.8 ± 1.2	6.8 ± 1.4	<0.0001
TG (mg/dl)	152 ± 114	167 ± 110	NS
TC (mg/dl)	176 ± 45	201 ± 49	0.0096
HDL (mg/dl)	48 ± 8	50 ± 11	NS
LDL (mg/dl)	109 ± 38	125 ± 39	0.0435
Albumin (g/dl)	4.4 ± 0.4	4.4 ± 0.4	NS
Na^+ (mEq/l)	142 ± 2	140 ± 3	0.0003
K^+ (mEq/l)	4.6 ± 0.4	4.9 ± 0.6	0.0106
Ca^++ (mg/dl)	9.1 ± 0.4	9.2 ± 0.5	NS
iPO4^- (mg/dl)	3.3 ± 0.4	3.5 ± 0.7	0.0117
GFR (ml/min/1.73m²)	123 ± 31	44 ± 29	<0.0001
UPE (mg/day)	73 ± 32	994 ± 1234	<0.0001
UAE (mg/day)	11 ± 10	677 ± 905	<0.0001
UNaE (mEq/day)	152 ± 56	142 ± 95	NS
iPTH (ng/ml)	61.2 ± 25.3	154.7 ± 143.2	<0.0001
Hemoglobin (gr/ dl)	13.8 ± 1.4	12.7 ± 1.8
Platelet (10^3/μl)	248 ± 53	253 ± 65	NS
Mean CIMT (mm)	0.520 ± 0.052	0.786 ± 0.168	<0.0001
CRP (mg/dl)	0.31 ± 0.22	0.68 ± 0.94	0.0013
Fetuin-A (ng/ml)	95.4 ± 16	84.4 ± 22.3	0.0202
OPG (ng/ml)	12.9 ± 8.6	18.5 ± 10.7	0.0047
MGP (ng/ml)	3.0 ± 2.8	1.5 ± 1.6	0.0003

NS: not significant; BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; FPG: fasting plasma glucose; TG: triglyceride; TC: total cholesterol; HDL: high-density lipoprotein; LDL: low-density lipoprotein; GFR: glomerular filtration rate; UPE: urinary protein excretion; UAE: urinary albumin excretion; UNaE: urinary sodium excretion; iPTH: intact parathyroid hormone; CIMT: carotid intima-media thickness; CRP: C-reactive protein; OPG: osteoprotegerin; MGP: matrix GLA protein.

Table 2. Comparison of demographic, clinical and laboratory data of healthy control group and patient groups according to CKD stages.

	HC (n = 32)	Stage 2 (n = 26)	Stage 3 (n = 34)	Stage 4 (n = 23)	Stage 5 (n = 8)
Age (years)	46.2 ± 10.4	46.1 ± 11.4	47.4 ± 11.5	46.2 ± 8.1	47.4 ± 7.2
BMI (kg/m^2)	25.9 ± 4.0	25.6 ± 3	26.1 ± 3.6	26.5 ± 4.2	26.3 ± 3.7
SBP (mmHg)	118 ± 9	127 ± 13**	129 ± 14***	138 ± 18***	133 ± 17***
DBP (mmHg)	75 ± 6	82 ± 12*	83 ± 11**	86 ± 11***	86 ± 13**
FPG (mg/dl)	83 ± 11	87 ± 10	89 ± 8*	88 ± 9	84 ± 14
Urea (mg/dl)	29 ± 9	37 ± 11*	60 ± 23***	99 ± 28^***,a	119 ± 18^***,a
Creatinine (mg/dl)	0.7 ± 0.2	1.0 ± 0.2***	1.7 ± 0.6***	3.5 ± 0.9^***,a	4.7 ± 0.7^***,a,b
Uric Acid (mg/dl)	4.8 ± 1.2	6 ± 1.4**	6.8 ± 1.3***	7.5 ± 1.3***	7 ± 1.3***
TG (mg/dl)	152 ± 114	157 ± 102	181 ± 130	165 ± 105	152 ± 71
TC (mg/dl)	176 ± 45	214 ± 56**	200 ± 48*	189 ± 41	198 ± 49
HDL (mg/dl)	48 ± 8	53 ± 10	50 ± 11	46 ± 12	51 ± 12
LDL (mg/dl)	109 ± 38	137 ± 43*	128 ± 37*	112 ± 36	115 ± 31
Albumin (g/dl)	4.4 ± 0.4	4.3 ± 0.5	4.5 ± 0.2	4.3 ± 0.3	4.5 ± 0.2
Na^+ (mEq/l)	142 ± 2	140 ± 2**	140 ± 3**	139 ± 3**	140 ± 3
K^+ (mEq/l)	4.6 ± 0.4	4.8 ± 0.5	4.9 ± 0.6*	4.8 ± 0.7	5.1 ± 0.9*
Ca^++ (mg/dl)	9.1 ± 0.4	9.3 ± 0.5	9.4 ± 0.4	8.8 ± 0.5^*,a	9.2 ± 0.6
iPO4^- (mg/dl)	3.3 ± 0.4	3.2 ± 0.5	3.4 ± 0.5	3.9 ± 0.6^****,a	4.3 ± 0.6^***,a
GFR (ml/min/1.73m²)	123 ± 31	75.5 ± 9.4***	42.8 ± 9.3***	21.7 ± 4.5^****,a	12.1 ± 2^***,a,b
UPE (mg/day)	73 ± 32	603 ± 974***	760 ± 1013***	1603 ± 1591^***,a	1582 ± 1049^***,a
UAE (mg/day)	11 ± 10	609 ± 1028***	549 ± 721***	879 ± 1098***	966 ± 621***
UNaE (mEq/day)	152 ± 56	146 ± 67	158 ± 135	117 ± 59*	134 ± 38
iPTH (ng/ml)	61 ± 25	83 ± 43*	132 ± 184**	219 ± 86^***,a	290 ± 145^***,a
Hemoglobin (g/ dl)	13.8 ± 1.4	13.8 ± 1.1	13 ± 1.7*	11.5 ± 1.7^***,a	12.1 ± 0.9***
Platelet (10^3/μl)	248 ± 53	267 ± 68	253 ± 49	258 ± 78	199 ± 59*
Mean CIMT (mm)	0.520 ± 0.052	0.752 ± 0.170***	0.778 ± 0.154***	0.794 ± 0.148***	0.911 ± 0.249***
CRP (mg/dl)	0.31 ± 0.22	0.4 ± 0.3	0.6 ± 0.9*	0.9 ± 1.4**	0.9 ± 0.8***
Fetuin-A (ng/ml)	95.4 ± 16	99.1 ± 7.3	82.1 ± 24.4*	85.3 ± 22.6	77.7 ± 20.2*
OPG (ng/ml)	12.9 ± 8.6	18.3 ± 10.3*	17.9 ± 10.2*	18.2 ± 13.2	22.4 ± 7.3*
MGP (ng/ml)	3.0 ± 2.8	2.0 ± 2.4*	1.4 ± 1.5**	1.3 ± 0.9**	1.1 ± 1.0**

HC: healthy control; NS: not significant; BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; FPG: fasting plasma glucose; TG: triglyceride; TC: total cholesterol; HDL: high-density lipoprotein; LDL: low-density lipoprotein; GFR: glomerular filtration rate; UPE: urinary protein excretion; UAE: urinary albumin excretion; UNaE: urinary sodium excretion; iPTH: intact parathyroid hormone; CIMT: carotid intima media thickness; CRP: C-reactive protein; OPG: osteoprotegerin; MGP: matrix GLA protein.

In comparison of healthy control group and CKD groups *p < 0.05, **p = 0 < 0.005, ***p < 0.0005.

In the comparison of stage 2 and stage 3, stage 4 and stage 5 patients, ^ap < 0.05.

In the comparison of stage 3 and stage 4 and stage 5 patients.

In the comparison of stage 4 and stage 5 patients, ^bp < 0.05.

Table 3. Comparison of demographic, clinical and laboratory data of chronic kidney diseases patients with and without subclinical atherosclerosis.

Parameters	CIMT < 0.750 mm (n = 42)	CIMT > 0.750 mm (n = 50)	p
Age (years)	42 ± 11	51 ± 8	0.0000
BMI (kg/m^2)	25.1 ± 3.5	27.4 ± 3.6	0.0087
SBP (mmHg)	126 ± 15	136 ± 15	0.0041
DBP (mmHg)	81 ± 11	86 ± 11	0.0171
FPG (mg/dl)	86 ± 9	89 ± 9	NS
Urea (mg/dl)	60 ± 31	76 ± 37	0.0275
Creatinine (mg/dl)	1.9 ± 1.2	2.5 ± 1.4	0.0355
Uric Acid (mg/dl)	6.6 ± 1.2	6.9 ± 1.6	NS
TG (mg/dl)	147 ± 97	184 ± 119	NS
TC (mg/dl)	202 ± 48	200 ± 51	NS
HDL (mg/dl)	53 ± 11	47 ± 11	0.0152
LDL (mg/dl)	125 ± 35	125 ± 42	NS
Albumin (g/dl)	4.4 ± 0.4	4.4 ± 0.3	NS
Na^+ (mEq/l)	140 ± 3	140 ± 3	NS
K^+ (mEq/l)	4.9 ± 0.7	4.9 ± 0.6	NS
Ca^++ (mg/dl)	9.2 ± 0.5	9.2 ± 0.6	NS
iPO4^- (mg/dl)	3.4 ± 0.6	3.7 ± 0.7	0.0791
GFR (ml/min/1.73m²)	47.9 ± 21.9	40.3 ± 25.1	NS
UPE (mg/day)	1078 ± 1194	924 ± 1273	0.0002
UAE (mg/day)	784 ± 927	584 ± 886	0.0072
UNaE (mEq/day)	131 ± 62	151 ± 116	NS
iPTH (ng/ml)	168 ± 186	144 ± 95	<0.0001
Hemoglobin (g/ dl)	12.8 ± 1.8	12.6 ± 1.8	NS
Platelet (10^3/μl)	256 ± 65	249 ± 66	NS
Mean CIMT (mm)	0.659 ± 0.083	0.893 ± 0.146	0.893 ± 0.146
CRP (mg/dl)	0.4 ± 0.27	0.91 ± 1.21	0.0072
Fetuin-A (ng/ml)	91.3 ± 16.7	78.4 ± 24.9	0.0269
OPG (ng/ml)	18.7 ± 9	18.3 ± 12	NS
MGP (ng/ml)	1.6 ± 1.8	1.4 ± 1.5	NS

NS: not significant; BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; FPG: fasting plasma glucose; TG: triglyceride; TC: total cholesterol; HDL: high-density lipoprotein; LDL: low-density lipoprotein; GFR: glomerular filtration rate; UPE: urinary protein excretion; UAE: urinary albumin excretion; UNaE: urinary sodium excretion; iPTH: intact parathyroid hormone; CIMT: carotid intima-media thickness; CRP: C-reactive protein; OPG: osteoprotegerin; MGP: matrix GLA protein.

Figure 1. Relationship between CIMT and age, BMI, fetuin-A and OPG.

Table 4. Evaluation of multiple relationships between carotid artery intima-media thickness and other values in patients with chronic kidney disease.

Parameters	r	p
Age (years)	0.493	<0.001
BMI (kg/m^2)	0.337	0.001
CRP (mg/dl)	0.301	0.004
TG (mg/dl)	0.245	0.019
Urea (mg/dl)	0.228	0.029
SPB (mmHg)	0.212	0.043
FPG (mg/dl)	0.212	0.043
Fetuin-A (ng/ml)	–0.409	0.001
OPG (ng/ml)	–0.235	0.024
GFR (ml/min/1.73m²)	–0.209	0.046

Table 5. Evaluation of multiple relationships between fetuin-A, osteoprotegerin and matrix GLA protein and other data in patients with chronic kidney disease.

	Parameters	r	p
Fetuin-A (ng/ml)	CIMT (mm)	−0.417	0.001
	Urea (mg/dl)	−0.353	0.007
	CRP (mg/dl)	−0.322	0.014
	Creatinine (mg/dl)	−0.277	0.035
	Age (years)	−0.262	0.047
Osteoprotegrin (ng/ml)	CIMT (mm)	−0.235	0.024
Matrx GLA protein (ng/ml)	Age (years)	−0.222	0.033
	BMI (kg/m^2)	−0.215	0.040

Table 6. Evaluation of the independent determinants of the increase in CIMT.

Model	Factor	p	Impact (%95 Cl)
*p = 0.00015 R^2=0.246	Fetuin-A	0.007	1 ng/ml Decrease, 0.0026 (0.0007–0.0045) mm CIMT increase
	Age	0.008	1 Year increase, 0.0061 (0.0017–0.0106) mm CIMT increase

CIMT: carotid intima-media thickness.

*Multivariate linear logistic regression analysis (model stepwise).

Figure 2. Evaluation of the power of fetuin-A level to determine the presence of subclinical atherosclerosis in the CKD group.