Study on the correlation between serum dp-ucMGP level and vascular calcification in maintenance hemodialysis patients

doi:10.3877/cma.j.issn.2095-3216.2021.06.003

Abstract

Abstract:

Objective

To investigate the correlation between serum dephosphorylated-uncarboxylated matrix glutamate protein (dp-ucMGP) and coronary artery calcification in maintenance hemodialysis (MHD) patients.

Methods

A total of 89 MHD patients and 40 healthy persons as the control were selected. Chest CT examination and coronary artery calcification score calculation were performed. The serum vitamin K2, dp-ucMGP, uncarboxylated matrix glutamate protein (ucMGP), calcium, phosphorus, intact parathyroid hormone, and other indicators were measured. The correlation between coronary calcification score and dp-ucMGP and others was analyzed with the Spearman correlation analysis method.

Results

The serum dp-ucMGP level of MHD patients group was higher than that of the control group (13.5±2.65 vs 7.16±2.09 ng/ml, P<0.01). The coronary artery calcification score in MHD group was positively correlated with the serum dp-ucMGP level (r=0.59, P<0.01), but not with the ucMGP level (r=-0.11, P=0.30). In the MHD patient group, when dp-ucMGP was used to diagnose coronary calcification, and the receiver operating characteristic curve (ROC) was drawn. The area under the curve was 0.769 (95%CI: 0.661-0.877, P<0.001), indicating that dp-ucMGP was of significane for the diagnosis of coronary artery calcification.

Conclusion

The serum dp-ucMGP level of MHD patients was higher than that of the normal control, and had a positive correlation with the coronary calcification score. Detection of the serum dp-ucMGP rather than the ucMGP may be helpful for evaluating the coronary calcification in MHD patients.

Key words: Dp-ucMGP, Vitamin K2, Hemodialysis, Vascular calcification

Youxin Wei, Yuanping Wu, Baisheng Chen, Changying Xing. Study on the correlation between serum dp-ucMGP level and vascular calcification in maintenance hemodialysis patients[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2021, 10(06): 311-316.

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Figures/Tables 7

References 24

[1]	Staude H, Jeske S, Schmitz K, et al. Cardiovascular risk and mineral bone -disorder in patients with chronic kidney disease [J]. Kidney Blood Press Res, 2013, 37(1): 68-83.
[2]	Miller EO, Schwartz RG. Cardiovascular risk assessment with regadenoson SPECT MPI in patients with end-stage renal disease is safe, effective, and well tolerated: does it matter? [J]. J Nucl Cardiol, 2017, 24(1): 119-121.
[3]	Schurgers LJ, Uitto J, Reutelingsperger CP. Vitamin K-dependent carboxylation of matrix Gla-protein: a crucial switch to control ectopic mineralization [J]. Trends Mol Med, 2013, 19(4): 217-226.
[4]	Price PA, Otsuka AA, Poser JW, et al. Characterization of a gamma-carboxyglutamic acid-containing protein from bone [J]. Proc Natl Acad Sci USA, 1976, 73(5): 1447-1451.
[5]	Chiyoya M, Seya K, Yu Z, et al. Matrix Gla protein negatively regulates calcification of human aortic valve interstitial cells isolated from calcified aortic valves [J]. J Pharmacol Sci, 2018, 136(4): 257-265.
[6]	Ciprian N, Tamas I, Vladimir P, et al. Vitamin K dependent proteins in kidney disease [J]. Int J Mol Sc, 2019, 20(7): 1571.
[7]	Hilary B, Mary O, Eamon K, et al. Is matrix Gla protein associated with vascular calcification? a systematic review [J]. Nutrients, 2018, 10(4): 415.
[8]	Bjørklund G, Svanberg E, Dadar M, et al. The role of matrix Gla protein (MGP) in vascular calcification [J]. Curr Med Chem, 2020, 27(10): 1647-1660.
[9]	Westenfeld R, Vermeer C, Schlieper G, et al. Circulating nonphosphorylated carboxylated matrix Gla protein predicts survival in ESRD [J]. J Am Soc Nephrol, 2011, 22(2): 387-395.
[10]	Meuwese CL, Olauson H, Qureshi AR. et al. Associations between thyroid hormones, calcifification inhibitor levels and vascular calcification in end-stage renal disease [J]. PLoS One, 2015, 10(7): e0132353.
[11]	Delanaye P, Krzesinski JM, Warling X, et al. Dephosphorylated-uncarboxylated matrix Gla protein concentration is predictive of vitamin K status and is correlated with vascular calcification in a cohort of hemodialysis patients [J]. BMC Nephrol, 2014, 15: 145.
[12]	Schurgers LJ, Barreto DV, Barreto FC, et al. The circulating inactive form of matrix Gla protein Is a surrogate marker for vascular calcification in chronic kidney disease: a preliminary report [J]. Clin J Am Soc Nephrol, 2010, 5(4): 568-575.
[13]	Jaminon A, Lu D, Qureshi AR, et al. Matrix Gla protein is an independent predictor of both intimal and medial vascular calcification in chronic kidney disease [J]. Sci Rep, 2020, 10(1): 6586.
[14]	Li Y, Xie QH, You HZ, et al. Twelve weeks of pioglitazone therapy significantly attenuates dysmetabolism and reduces inflammation in continuous ambulatory peritoneal dialysis patients--a randomized crossover trial [J]. Perit Dial Int, 2012, 32(5): 507-515.
[15]	Hackeng TM, Rosing J, Spronk H, et al. Total chemical synthesis of human matrix Gla protein [J]. Protein Sci, 2010, 10(4): 864-870.
[16]	Luo G, Ducy P, McKee MD, et al. Spontaneous calcification of arteries and cartilage in mice lacking matrix Gla protein [J]. Nature, 1997, 386(6620): 78-81.
[17]	Chiyoya M, Seya K, Yu Z, et al. Matrix Gla protein negatively regulates calcification of human aortic valve interstitial cells isolated from calcified aortic valves [J]. J Pharmacol Sci, 2018, 136(4): 257-265.
[18]	Wei FF, Trenson S, Verhamme P, et al. Vitamin K-dependent matrix Gla protein as multifaceted protector of vascular and tissue integrity [J]. Hypertension, 2019, 73(6): 1160-1169.
[19]	Ahmad S, Jan AT, Baig MH, et al. Matrix Gla protein: an extracellular matrix protein regulates myostatin expression in the muscle developmental program [J]. Life Sci, 2017, 172: 55-63.
[20]	Cranenburg ECM, Schurgers LJ, Uiterwijk HH, et al. Vitamin K intake and status are low in hemodialysis patients [J]. Kidney Int, 2012, 82(5): 605-610.
[21]	Wyskida K, Ak-Gob A, Wajda J, et al. Functional deficiency of vitamin K in hemodialysis patients in Upper Silesia in Poland [J]. Int Urol Nephrol, 2016, 48(5): 765-771.
[22]	Aoun M, Makki M, Azar H, et al. High dephosphorylated-uncarboxylated MGP in hemodialysis patients: risk factors and response to vitamin K2, a pre-post intervention clinical trial [J]. BMC Nephrol, 2017, 18(1): 191.
[23]	Schurgers LJ, Joosen IA, Laufer EM, et al. Vitamin K-antagonists accelerate atherosclerotic calcification and induce a vulnerable plaque phenotype [J]. PLoS One, 2012, 7(8): e43229.
[24]	Zanoli L, Lentini P, Briet M, et al. Arterial stiffness in the heart disease of CKD [J]. J Am Soc Nephrol, 2019, 30(6): 918-928.

项目	对照组(n＝40)	病例组(n＝89)	t/Z/χ²值	P值
年龄(岁)	59.80±13.14	62.29±14.36	-0.94	0.35
男/女(例)	22/18	45/44	0.22	0.64
血红蛋白(g/L)	141.73±13.33	96.27±21.21	14.75	<0.01
钙(mmol/L)	2.31±0.15	2.19±0.27	3.19	<0.01
磷(mmol/L)	1.22±0.19	1.63±0.50	-6.69	<0.01
C反应蛋白(mg/L)	0.40(0.13，0.68)	4.55(0.23，33.27)	-4.31	<0.01
白蛋白(g/L)	44.56±6.44	38.46±5.54	5.19	<0.01
甘油三酯(mmol/L)	1.15(0.88，1.66)	1.49(0.93，2.13)	-1.47	0.14
全段甲状旁腺激素(ng/L)	37(23，54)	364(205，619)	-9.06	<0.01
维生素K₂(nmol/L)	7.67(6.65，8.24)	3.09(1.97，5.15)	-8.76	<0.01
ucMGP(ng/ml)	11.13(9.51，11.78)	5.74(4.08，7.16)	-8.92	<0.01
dp-ucMGP(ng/ml)	7.16±2.09	13.47±2.65	-13.30	<0.01
钙化积分	0.0(0.0，0.0)	263.1(33.1，845.7)	-8.02	<0.01

项目	对照组(n＝40)	病例组(n＝89)	t/Z/χ²值	P值
年龄(岁)	59.80±13.14	62.29±14.36	-0.94	0.35
男/女(例)	22/18	45/44	0.22	0.64
血红蛋白(g/L)	141.73±13.33	96.27±21.21	14.75	<0.01
钙(mmol/L)	2.31±0.15	2.19±0.27	3.19	<0.01
磷(mmol/L)	1.22±0.19	1.63±0.50	-6.69	<0.01
C反应蛋白(mg/L)	0.40(0.13，0.68)	4.55(0.23，33.27)	-4.31	<0.01
白蛋白(g/L)	44.56±6.44	38.46±5.54	5.19	<0.01
甘油三酯(mmol/L)	1.15(0.88，1.66)	1.49(0.93，2.13)	-1.47	0.14
全段甲状旁腺激素(ng/L)	37(23，54)	364(205，619)	-9.06	<0.01
维生素K₂(nmol/L)	7.67(6.65，8.24)	3.09(1.97，5.15)	-8.76	<0.01
ucMGP(ng/ml)	11.13(9.51，11.78)	5.74(4.08，7.16)	-8.92	<0.01
dp-ucMGP(ng/ml)	7.16±2.09	13.47±2.65	-13.30	<0.01
钙化积分	0.0(0.0，0.0)	263.1(33.1，845.7)	-8.02	<0.01

项目	无钙化组(n＝27)	低分钙化组(n＝28)	高分钙化组(n＝34)	F/H/χ²值	P值
年龄(岁)	61.6±14.7	61.8±13.5	63.3±15.1	0.13	0.88
男/女(例)	13/14	14/14	18/16	0.14	0.93
血红蛋白(g/L)	102.9±26.9	93.9±15.7	92.9±19.4	1.97	0.25
C反应蛋白(mg/L)	2.36(0.51，21.4)	2.84(0.11，25.7)	10.2(0.46，41.7)	1.60	0.45
钙(mmol/L)	2.22±0.23	2.18±0.36	2.18±0.23	0.25	0.78
磷(mmol/L)	1.35(1.12，1.65)	1.61(1.37，1.93)	1.65 (1.41，2.20)^a	9.33	<0.01
白蛋白(g/L)	39.1±5.50	38.7±5.90	37.8±5.36	0.49	0.61
甘油三酯(mmol/L)	1.40(0.88，1.93)	1.56(0.98，2.27)	1.60(0.96，2.06)	0.51	0.78
全段甲状旁腺激素(ng/L)	197(110，356)	338(140，463)	642(453，961) ^ab	47.4	<0.01
维生素K₂(nmol/L)	4.98(3.21，5.87)	3.71(2.05，4.91)	2.13(1.43，2.80)^a	20.9	<0.01
ucMGP(ng/ml)	5.71(4.28，6.98)	5.96(3.46，7.56)	5.62(3.78，7.02)	0.46	0.79
dp-ucMGP(ng/ml)	11.8±2.24	12.9±1.97	15.3±2.38ab	19.9	<0.01

项目	无钙化组(n＝27)	低分钙化组(n＝28)	高分钙化组(n＝34)	F/H/χ²值	P值
年龄(岁)	61.6±14.7	61.8±13.5	63.3±15.1	0.13	0.88
男/女(例)	13/14	14/14	18/16	0.14	0.93
血红蛋白(g/L)	102.9±26.9	93.9±15.7	92.9±19.4	1.97	0.25
C反应蛋白(mg/L)	2.36(0.51，21.4)	2.84(0.11，25.7)	10.2(0.46，41.7)	1.60	0.45
钙(mmol/L)	2.22±0.23	2.18±0.36	2.18±0.23	0.25	0.78
磷(mmol/L)	1.35(1.12，1.65)	1.61(1.37，1.93)	1.65 (1.41，2.20)^a	9.33	<0.01
白蛋白(g/L)	39.1±5.50	38.7±5.90	37.8±5.36	0.49	0.61
甘油三酯(mmol/L)	1.40(0.88，1.93)	1.56(0.98，2.27)	1.60(0.96，2.06)	0.51	0.78
全段甲状旁腺激素(ng/L)	197(110，356)	338(140，463)	642(453，961) ^ab	47.4	<0.01
维生素K₂(nmol/L)	4.98(3.21，5.87)	3.71(2.05，4.91)	2.13(1.43，2.80)^a	20.9	<0.01
ucMGP(ng/ml)	5.71(4.28，6.98)	5.96(3.46，7.56)	5.62(3.78，7.02)	0.46	0.79
dp-ucMGP(ng/ml)	11.8±2.24	12.9±1.97	15.3±2.38ab	19.9	<0.01

项目	回归系数	标准误	标准化回归系数	t值	P值
常量	-11.153	4.721		-2.362	0.020
全段甲状旁腺激素(X1)	0.021	0.003	0.467	6.676	<0.001
dp-ucMGP(X2)	1.614	0.316	0.321	5.102	<0.001
维生素K2(X3)	-2.149	0.447	-0.281	-4.810	<0.001
血磷(X4)	3.455	1.583	0.131	2.183	0.032

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