Association between serum elastin-derived peptides and abdominal aortic calcification in peritoneal dialysis patients: a cross-sectional study

Figures & data

Figure 1. Flowchart of study participants for the cross-sectional study. AAC indicates abdominal aortic calcification.

Figure 2. Cross-sectional view of abdominal aortic calcification by CT in four representative cases.

Table 1. Comparisons of demographic data and laboratory parameters among PD patients with or without AAC and the controls.

	Control	All PD patients	Non-AAC	AAC
	N = 30	N = 126	N = 41	N = 85
Age, year	47 ± 8	50 ± 13	41 ± 11	55 ± 11^b, c
Male n,(%)	17 (60.7)	75 (59.5)	23 (56.1)	52 (61.2)
SBP, mmHg	119 ± 9^a	147 ± 18	145 (139 − 156)^c	145 (136 − 155)^c
DBP, mmHg	72 ± 10^a	85 ± 12	89 ± 14^c	83 ± 10^b, c
BMI, kg/m^2	NA	23.3± 3.2	22.5 (21.3 − 26.2)	23.4 (21.3 − 25.0)
HBP n, (%)	0	125 (99.2)	41 (100.0)	84 (98.8)
T2DM n, (%)	0	12 (9.5)	3 (7.3)	9 (10.6)
CVD n, (%)	0	9 (7.1)	2 (4.9)	7 (8.2)
PD vintage, month	NA	22.5 (7.0 − 51.0)	12.0 (5.5 − 24.5)	39.0 (9.0 − 61.5)^b
total Kt/V	NA	1.81 (1.62 − 2.05)	1.74 (1.51 − 2.17)	1.86 (1.67 − 2.04)
HB, g/L	135 ± 19^a	99 ± 16	102 ± 17^c	98 ± 16^c
NE, 10^9/L	3.5(2.9 − 4.4)	3.7(2.8 − 4.6)	3.4 (2.6 − 4.4)	3.7(2.8 − 4.6)
PLT, 10^6/L	237 ± 64^a	171 ± 56	183 ± 55^c	166 ± 56^c
TG, mmol/L	1.2 (0.9 – 1.6)	1.4 (1.0 – 2.0)	1.4 (1.1 – 1.9)	1.4 (1.0 – 2.0)
TC, mmol/L	4.57 ± 0.93	4.41 ± 1.09	4.44 ± 1.07	4.39 ± 1.10
HDL, mmol/L	1.12 (0.93 − 1.31)^a	0.97 (0.81 − 1.19)	0.95 (0.79 − 1.21)	0.98 (0.82 − 1.19)
LDL, mmol/L	2.82 ± 0.85^a	2.20 ± 0.78	2.24 ± 0.69^c	2.18 ± 0.82^c
Cr, µmol/L	63 ± 13^a	944 ± 292	991 ± 303^c	921 ± 286^c
β2-MG, mg/L	NA	28.3 (20.820.8 − 34.3)	27.2 ± 11.3	29.1 ± 10.5
UA, mmol/L	315 ± 100^a	390 ± 72	416 ± 80^c	379 ± 65^b, c
Alb, g/L	44.0 (41.3 − 46.0)^a	34.6 (31.3 − 37.13)	34.9 ± 3.5^c	33.3 ± 5.1^b, c
Ca, mmol/L	2.29 ± 0.13	2.25 ± 0.19	2.16 ± 0.14	2.16 ± 0.20
P, mmol/L	1.24 ± 0.27^a	1.63 ± 0.40	1.71 ± 0.45^c	1.59 ± 0.37^c
hs-CRP, mg/L	1.9 (0.8 − 3.3)	1.9 (0.7 − 4.3)	1.7 (0.4 − 4.8)	2.0 (0.9 − 4.0)
ALP, U/L	57 (47 − 70)^a	80 (63 − 116)	66 (54 − 94)^c	88 (71 − 136)^b, c
iPTH, ng/L	NA	397 (26 − 595)	358 (224 − 542)	405 (266 − 656)
EDPs, ng/mL	31.7 (24.2 − 39.2)^a	46.0 (37.7 − 55.0)	37.7 (32.3 − 46.5)^c	48.3 (42.8 − 57.4)^b,c

Data are presented as mean ± SD, median (Q1–Q3), or frequency (percentage). NA means not assessed. ^ap < 0.05 when comparing between two groups of all PD patients and controls. ^bp < 0.05 when comparing between two groups of PD patients with and without AAC. ^cp < 0.05 in the post-hoc analysis between AAC group with controls or non-AAC group with controls.

AAC indicates abdominal aortic calcification; PD: peritoneal dialysis; SBP: systole blood pressure; DBP: diastole blood pressure; BMI: body mass index; T2DM: type 2 diabetes mellitus; CVD: cardiovascular disease; Kt/V: weekly urea clearance; HB: hemoglobin; NE: neutrophil; PLT: platelet; TG: triglyceride; TC: total cholesterol; HDL: high-density lipoprotein; LDL: low-density lipoprotein; Cr: creatinine; β2-MG: β2-microglobulin; UA: uric acid; Alb: albumin; Ca: calcium; P: phosphate; hs-CRP: high sensitivity C reactive protein; ALP: alkaline phosphatase; iPTH: intact parathyroid hormone; EDPs: elastin-derived peptides.

Figure 3. Correlation analyses of EDPs with other parameters in PD patients. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001

Figure 4. Comparisons of EDPs among different groups presented as a dot-plot. EDPs of PD patients with or without AAC were greatly higher than healthy controls. In all PD patients, EDPs of AAC were significantly higher than those without AAC. In patients with severer AAC, EDPs were also higher than those without severer AAC. AAC indicates abdominal aortic calcification; PD: peritoneal dialysis; EDPs, elastin-derived peptides.

Figure 5. Receiver operating characteristic curves to predict AAC in PD patients. A combined model of age, PD vintage, UA, and EDPs yielded a significant increase in AUC when compared with other factors alone (Union factor 1, AUC = 0.903). The respective AUC of other parameters including EDPs, PD vintage, age, and UA was 0.766, 0.721), 0.813), and 0.645.

Table 2. Univariate and multivariate logistic regression analysis for effects of EDPs on AAC in PD patients.

	Parameters	Β	SE	Wald	OR	95% CI	p Value
Univariate logistic regression	Age, year	0.115	0.023	25.860	1.122	1.073–1.173	<0.001
	DBP, mmHg	−0.043	0.017	6.414	0.958	0.927–0.990	0.011
	PD vintage, month	0.040	0.011	14.311	1.041	1.019–1.062	<0.001
	UA, mmol/L	−0.008	0.003	6.958	0.992	0.986–0.998	0.008
	Alb, g/L	−0.077	0.044	3.039	0.926	0.850–1.010	0.081
	ALP, U/L	0.013	0.013	0.005	6.092	1.003–1.024	0.014
	EDPs, ng/mL	0.086	0.021	16.477	1.090	1.046–1.137	<0.001
Multivariate logistic regression	Age, year	0.093	0.027	11.942	1.097	1.041–1.156	0.001
	PD vintage, month	0.041	0.014	8.368	1.042	1.013–1.071	0.004
	EDPs, ng/mL	0.054	0.022	5.793	1.056	1.010–1.103	0.016
	UA, mmol/L	−0.013	0.004	10.307	0.987	0.979–0.995	0.001
Sensitivity analysis	Age, year	0.099	0.027	13.695	1.104	1.048–1.164	<0.001
	PD vintage, month	0.036	0.013	7.303	1.037	1.010–1.065	0.007
	EDPs (categorical data)	1.015	0.517	3.899	2.760	1.003–7.596	0.049
	UA, mmol/L	−0.012	0.004	8.899	0.988	0.981–0.996	0.003

Binomial logistic regression was analyzed with prevalent AAC as the outcome in all PD patients. The multivariate logistic regression was adjusted for age, DBP, PD vintage, history of T2DM, Alb, UA, Ca, P, ALP, iPTH, TC, and TG. Sensitivity analysis was conducted with EDPs included as a dichotomous variable according to its cutoff point in the ROC curve. OR means per 1 unit increment in an independent variable can lead to the change in the risk of AAC.

AAC indicates abdominal aortic calcification; PD: peritoneal dialysis; DBP: diastole blood pressure; Alb: albumin; Ca: calcium; P: phosphate; ALP: alkaline phosphatase; iPTH: intact parathyroid hormone; TG: triglyceride; TC: total cholesterol; UA: uric acid; EDPs: elastin-derived peptide; OR: odds ratio; and CI: confidence interval.

Table 3. Comparisons of demographic data and laboratory parameters with or without severer AAC in PD patients.

	PD		p Value
	Non severer AAC	Severer AAC
	N = 49	N = 36
Age, year	51 ± 11	60 ± 10	<0.001^***
Male n,(%)	30 (61.2)	22 (61.1)	1.000
SBP, mmHg	142 (135 − 148)	148 (142 − 160)	0.010^*
DBP, mmHg	81 (75 − 87)	86 (79 − 89)	0.068
BMI, kg/m2	22.9 ± 2.8	23.3 ± 2.7	0.456
Hypertension n,(%)	49 (100.0)	35 (97.2)	0.424
T2DM n,(%)	5 (10.2)	4 (11.1)	1.000
CVD n,(%)	3 (6.1)	4 (11.1)	0.45
PD vintage, month	12.0 (6.0 − 39.0)	58.5 (43.0 − 79.5)	<0.001^***
total Kt/V	1.98 (1.64 − 2.26)	1.81 (1.67 − 1.99)	0.118
HB, g/L	97 ± 14	97 ± 16	0.886
NE, 109/L	3.6 (2.8 − 4.6)	3.7 (2.9 − 5.1)	0.584
PLT, 106/L	163 ± 59	169 ± 52	0.666
TG, mmol/L	1.8 ± 1.2	1.5 ± 1.0	0.297
TC, mmol/L	4.39 ± 1.04	4.40 ± 1.20	0.996
HDL, mmol/L	1.02 ± 0.30	1.04 ± 0.32	0.692
LDL, mmol/L	2.19 ± 0.82	2.17 ± 0.81	0.920
Cr, µmol/L	863 ± 299	1000 ± 251	0.029^*
β2-MG, mg/L	26.4 ± 11.1	32.7 ± 8.6	0.004^**
UA, mmol/L	369 ± 57	391 ± 75	0.134
Alb, g/L	34.2 ± 5.2	32.2 ± 4.9	0.084
Ca, mmol/L	2.14 ± 0.19	2.18 ± 0.23	0.494
P, mmol/L	1.52 ± 0.38	1.68 ± 0.34	0.049^*
hs-CRP, mg/L	1.7 ( 0.6 − 3.1)	2.5 (1.9 − 4.7)	0.018^*
ALP, U/L	80 (69 − 138)	91 (74 − 127)	0.434
iPTH, ng/L	352 (245 − 535)	479 (361 − 714)	0.018^*
EDPs, ng/mL	47.6 (39.2 − 53.9)	53.8 (46.4 − 62.8)	0.003^**

Data are presented as mean ± SD, median (interquartile ranges), or frequency (percentage). ^*p < 0.05, ^**p < 0.01, ^***p < 0.001. AAC indicates abdominal aortic calcification; PD, peritoneal dialysis; SBP, systole blood pressure; DBP, diastole blood pressure; BMI, body mass index; T2DM, type-2 diabetes mellitus; CVD, cardiovascular disease; Kt/V, weekly urea clearance; HB, hemoglobin; NE, neutrophil; PLT, platelet; TG, triglyceride; TC, total cholesterol; HDL, high-density lipoprotein; LDL, low-density lipoprotein; Cr, creatinine; β2-MG, β2-microglobulin; UA, uric acid; Alb, albumin; Ca, calcium; P, phosphate; hs-CRP, high sensitivity C reactive protein; ALP, alkaline phosphatase; iPTH, intact parathyroid hormone; EDPs, elastin-derived peptide.

Figure 6. Receiver operating characteristic curves to predict severe AAC in PD patients. A combined model of age, PD vintage, P, and EDPs yielded a significant increase in AUC when compared with other factors alone (Union factor 2, AUC = 0.886). The respective AUC of other parameters including EDPs, PD vintage, age, and P was 0.681, 0.856, 0.715, and 0.633.

Table 4. Logistic regression analysis of EDPs on severer AAC in PD patients.

	parameters	β	SE	Wald	OR	95% CI	p Value
Univariate logistic regression	Age, year	0.069	0.022	9.697	1.072	1.026–1.120	0.002
	PD vintage, month	0.047	0.011	19.146	1.048	1.026–1.070	<0.001
	Total Kt/V	−1.029	0.553	3.469	0.357	0.121–1.055	0.063
	Cr, µmol/L	0.002	0.001	5.405	1.002	1.000–1.004	0.010
	β2-MG, mg/L	0.071	0.024	8.750	1.074	1.024–1.126	0.003
	P, mmol/L	1.348	0.649	4.315	3.851	1.079–13.740	0.038
	iPTH, ng/L	0.017	0.008	5.546	1.017	1.001–1.033	0.033
	EDPs, ng/mL	0.045	0.019	5.397	1.046	1.007–1.086	0.020
Multivariate logistic regression	Age, year	0.101	0.034	8.719	1.106	1.034–1.182	0.003
	PD vintage, month	0.043	0.012	13.418	1.044	1.020–1.069	<0.001
	P, mmol/L	3.237	1.192	7.379	25.468	2.464–263.288	0.007
	EDPs, ng/mL	0.060	0.029	4.394	1.062	1.004–1.123	0.036
Sensitivity analysis	Age, year	0.093	0.035	7.087	1.097	1.025–1.175	0.008
	PD vintage, month	0.044	0.012	12.683	1.044	1.020–1.070	<0.001
	P, mmol/L	3.088	1.203	6.585	21.931	2.074–231.928	0.010
	EDPs, ng/mL	1.875	0.692	7.337	6.521	1.679–25.322	0.007

Binomial logistic regression was analyzed with prevalent severer AAC as the outcome in patients with AAC. The multivariate logistic regression was adjusted for age, SBP, PD vintage, total kt/V, T2DM, Cr, β2-MG, P, and iPTH. Sensitivity analysis was conducted with EDPs included as a dichotomous variable according to the cutoff point in its ROC curve to predict severer AAC. OR means per 1 unit increment in an independent variable can lead to the change in the risk of severe AAC.

AAC indicates abdominal aortic calcification; PD: peritoneal dialysis; SBP: systole blood pressure; T2DM: type 2 diabetic mellitus; Cr: creatinine; β2-MG: β2-microglobulin; P: phosphate; iPTH: intact parathyroid hormone; EDPs: elastin-derived peptide; OR: odds ratio; and CI: confidence interval.

Data availability statement

The data that support the findings of this study are openly available in figshare at http://doi.org/10.6084/m9.figshare.13172660.