Background: Matrix Gla protein (MGP) is a potent inhibitor of vascular calcification and needs vitamin K-dependent carboxylation for its activity. High levels of desphosphorylated uncarboxylated MGP (dp-ucMGP) were significantly associated with vitamin K deficiency and vascular calcification. This study was conducted to explore the correlations of plasma dp-ucMGP with vascular calcification and vascular stiffness in chronic kidney disease (CKD) patients. Methods: This cross-sectional study enrolled 83 CKD stages 3-5 patients. Vascular calcification score was determined by calcific lesions in the abdominal aorta (AAC) shown by lateral lumbar film; vascular stiffness was assessed by cardio-ankle vascular index (CAVI) and pulse wave velocity, while plasma dp-ucMGP levels were measured using ELISA method. Multivariate regression analyses were used to select factors that were independently associated with vascular calcification and vascular stiffness. Results: The mean age was 62.9 ± 13.9 years. CKD stages 3, 4, and 5 constituted 51.8, 13.3, and 34.9%, respectively. The median of plasma dp-ucMGP levels in CKD stages 3, 4, and 5 were 586 (452-888), 870 (594-1,591), and 1,050 (518-1,298) pmol/L, respectively. The prevalence of vascular calcification (AAC score ≥1) was 63.4% and that of vascular stiffness (CAVI ≥9) was 46.3%. Vascular calcification was correlated with vascular stiffness (r2 = 0.50, p < 0.001). Multivariate logistic regression analysis models to predict vascular calcification showed that age and plasma dp-ucMGP levels were significantly correlated with vascular calcification (OR 1.21; 95% CI 1.09-1.33; p < 0.001 and OR 1.002; 95% CI 1.001-1.004; p = 0.004, respectively). In contrast, there was no association between plasma dp-ucMGP levels and vascular stiffness. Conclusions: Plasma dp-ucMGP levels increase according to the severity of CKD. Plasma dp-ucMGP was positively associated with vascular calcification and might be utilized as an early marker for vascular calcification in CKD patients.

Keywords:
Vascular calcification, Vascular stiffness, Cardio-ankle vascular index, Pulse wave velocity, Chronic kidney disease, Matrix Gla protein
1.
Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:1296-1305.
2.
Russo D, Palmiero G, De Blasio AP, Balletta MM, Andreucci VE: Coronary artery calcification in patients with CRF not undergoing dialysis. Am J Kidney Dis 2004;44:1024-1030.
3.
Spiegel DM, Raggi P, Mehta R, Lindberg JS, Chonchol M, Ehrlich J, et al: Coronary and aortic calcifications in patients new to dialysis. Hemodial Int 2004;8:265-272.
4.
Blacher J, Guerin AP, Pannier B, Marchais SJ, London GM: Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension 2001;38:938-942.
5.
Cannata-Andia JB, Roman-Garcia P, Hruska K: The connections between vascular calcification and bone health. Nephrol Dial Transplant 2011;26:3429-3436.
6.
Mackey RH, Venkitachalam L, Sutton-Tyrrell K: Calcifications, arterial stiffness and atherosclerosis. Adv Cardiol 2007;44:234-244.
7.
Mattace-Raso FU, van der Cammen TJ, Hofman A, van Popele NM, Bos ML, Schalekamp MA, et al: Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam study. Circulation 2006;113:657-663.
8.
Briet M, Boutouyrie P, Laurent S, London GM: Arterial stiffness and pulse pressure in CKD and ESRD. Kidney Int 2012;82:388-400.
9.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group: KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl 2009;113:S1-S130.
10.
Murshed M, Schinke T, McKee MD, Karsenty G: Extracellular matrix mineralization is regulated locally; different roles of two gla-containing proteins. J Cell Biol 2004;165:625-630.
11.
Cranenburg EC, Koos R, Schurgers LJ, Magdeleyns EJ, Schoonbrood TH, Landewe RB, et al: Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species. Thromb Haemost 2010;104:811-822.
12.
Boxma PY, van den Berg E, Geleijnse JM, Laverman GD, Schurgers LJ, Vermeer C, et al: Vitamin k intake and plasma desphospho-uncarboxylated matrix Gla-protein levels in kidney transplant recipients. PLoS One 2012;7:e47991.
13.
Schurgers LJ, Barreto DV, Barreto FC, Liabeuf S, Renard C, Magdeleyns EJ, et al: The circulating inactive form of matrix gla protein is a surrogate marker for vascular calcification in chronic kidney disease: a preliminary report. Clin J Am Soc Nephrol 2010;5:568-575.
14.
Stevens PE, Levin A; Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group Members: Evaluation and management of chronic kidney disease: synopsis of the kidney disease: improving global outcomes 2012 clinical practice guideline. Ann Intern Med 2013;158:825-830.
15.
National Kidney Foundation: K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003;42(4 suppl 3):S1-S201.
16.
Keyzer CA, Vermeer C, Joosten MM, Knapen MH, Drummen NE, Navis G, Bakker SJ, de Borst MH: Vitamin K status and mortality after kidney transplantation: a cohort study. Am J Kidney Dis 2015;65:474-483.
17.
Boxma PY, van den Berg E, Geleijnse JM, Laverman GD, Schurgers LJ, Vermeer C, Kema IP, Muskiet FA, Navis G, Bakker SJ, de Borst MH: Vitamin k intake and plasma desphospho-uncarboxylated matrix Gla-protein levels in kidney transplant recipients. PLoS One 2012;7:e47991.
18.
Kauppila LI, Polak JF, Cupples LA, Hannan MT, Kiel DP, Wilson PW: New indices to classify location, severity and progression of calcific lesions in the abdominal aorta: a 25-year follow-up study. Atherosclerosis 1997;132:245-250.
19.
Sun CK: Cardio-ankle vascular index (CAVI) as an indicator of arterial stiffness. Integr Blood Press Control 2013;6:27-38.
20.
Accetto R, Salobir B, Brguljan J, Rener K: Clinical implication of pulse wave analysis. Sci J Fac Med Niš 2010;27:165-169.
21.
Schurgers LJ, Spronk HM, Soute BA, Schiffers PM, DeMey JG, Vermeer C: Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats. Blood 2007;109:2823-2831.
22.
Dalmeijer GW, van der Schouw YT, Vermeer C, Magdeleyns EJ, Schurgers LJ, Beulens JW: Circulating matrix Gla protein is associated with coronary artery calcification and vitamin K status in healthy women. J Nutr Biochem 2013;24:624-628.
23.
Boxma PY, van den Berg E, Geleijnse JM, Laverman GD, Schurgers LJ, et al: Vitamin k intake and plasma desphospho-uncarboxylated matrix Gla-protein levels in kidney transplant recipients. PLoS One 2012;7:e47991.
24.
McCabe KM, Adams MA, Holden RM: Vitamin K status in chronic kidney disease. Nutrients 2013;5:4390-4398.
25.
Cheung CL, Sahni S, Cheung BM, Sing CW, Wong IC: Vitamin K intake and mortality in people with chronic kidney disease from NHANES III. Clin Nutr 2015;34:235-240.
26.
Caluwe R, Vandecasteele S, Van Vlem B, Vermeer C, De Vriese AS: Vitamin K2 supplementation in haemodialysis patients: a randomized dose-finding study. Nephrol Dial Transplant 2014;29:1385-1390.
27.
Wei FF, Drummen NE, Schutte AE, Thijs L, Jacobs L, Petit T, et al: Vitamin K dependent protection of renal function in multi-ethnic population studies. EBioMedicine 2016;4:162-169.
28.
Toussaint ND, Kerr PG: Vascular calcification and arterial stiffness in chronic kidney disease: implications and management. Nephrology (Carlton) 2007;12:500-509.
29.
Garnier AS, Briet M: Arterial stiffness and chronic kidney disease. Pulse (Basel) 2016;3:229-241.
30.
Briet M, Boutouyrie P, Laurent S, London GM: Arterial stiffness and pulse pressure in CKD and ESRD. Kidney Int 2012;82:388-400.
31.
Pivin E, Ponte B, Pruijm M, Ackermann D, Guessous I, Ehret G, et al: Inactive matrix Gla-protein is associated with arterial stiffness in an adult population-based study. Hypertension 2015;66:85-92.
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2016
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