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http://dx.doi.org/10.3346/jkms.2018.33.e322

The Correlation of Serum Osteoprotegerin with Non-Traditional Cardiovascular Risk Factors and Arterial Stiffness in Patients with Pre-Dialysis Chronic Kidney Disease: Results from the KNOW-CKD Study  

Chae, Seung Yun (Department of Internal Medicine, College of Medicine, The Catholic University of Korea)
Chung, WooKyung (Department of Internal Medicine, Gil Medical Center, Gachon University)
Kim, Yeong Hoon (Department of Internal Medicine, Inje University Busan Paik Hospital)
Oh, Yun Kyu (Department of Internal Medicine, Seoul National University Boramae Medical Center)
Lee, Joongyub (Department of Prevention and Management, Inha University School of Medicine)
Choi, Kyu Hun (Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University)
Ahn, Curie (Department of Internal Medicine, Seoul National University Hospital)
Kim, Yong-Soo (Department of Internal Medicine, College of Medicine, The Catholic University of Korea)
Publication Information
Journal of Korean Medical Science / v.33, no.53, 2018 , pp. 322.1-322.14 More about this Journal
Abstract
Background: Osteoprotegerin (OPG) plays protective roles against the development of vascular calcification (VC) which greatly contributes to the increased cardiovascular events in patients with chronic kidney disease (CKD). The present study aimed to find the non-traditional, kidney-related cardiovascular risk factors correlated to serum OPG and the effect of serum OPG on the arterial stiffness measured by brachial ankle pulse wave velocity (baPWV) in patients with the pre-dialysis CKD. Methods: We cross-sectionally analyzed the data from the patients in whom baPWV and the serum OPG were measured at the time of enrollment in a prospective pre-dialysis CKD cohort study in Korea. Results: Along with traditional cardiovascular risk factors such as age, diabetes mellitus, pulse pressure, and baPWV, non-traditional, kidney-related factors such as albuminuria, plasma level of hemoglobin, total $CO_2$ content, alkaline phosphatase, and corrected calcium were independent variables for serum OPG in multivariate linear regression. Reciprocally, the serum OPG was positively associated with baPWV in multivariate linear regression. The baPWV in the 3rd and 4th quartile groups of serum OPG were higher than that in the 1st quartile group after adjustments by age, sex and other significant factors for baPWV in linear mixed model. Conclusion: Non-traditional, kidney-related cardiovascular risk factors in addition to traditional cardiovascular risk factors were related to serum level of OPG in CKD. Serum OPG level was significantly related to baPWV. Our study suggests that kidney-related factors involved in CKD-specific pathways for VC play a role in the increased secretion of OPG into circulation in patients with CKD.
Keywords
Serum Osteoprotegerin; Non-Traditional Cardiovascular Risk Factors; Brachial-Ankle Pulse Wave Velocity; Chronic Kidney Disease;
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1 Morena M, Jaussent I, Dupuy AM, Bargnoux AS, Kuster N, Chenine L, et al. Osteoprotegerin and sclerostin in chronic kidney disease prior to dialysis: potential partners in vascular calcifications. Nephrol Dial Transplant 2015;30(8):1345-56.   DOI
2 Abedin M, Omland T, Ueland T, Khera A, Aukrust P, Murphy SA, et al. Relation of osteoprotegerin to coronary calcium and aortic plaque (from the Dallas Heart Study). Am J Cardiol 2007;99(4):513-8.   DOI
3 Lieb W, Gona P, Larson MG, Massaro JM, Lipinska I, Keaney JF Jr, et al. Biomarkers of the osteoprotegerin pathway: clinical correlates, subclinical disease, incident cardiovascular disease, and mortality. Arterioscler Thromb Vasc Biol 2010;30(9):1849-54.   DOI
4 Vik A, Brodin EE, Mathiesen EB, Brox J, Jorgensen L, Njolstad I, et al. Serum osteoprotegerin and renal function in the general population: the Tromso Study. Clin Kidney J 2017;10(1):38-44.
5 Nemeth ZK, Mardare NG, Czira ME, Deak G, Kiss I, Mathe Z, et al. Serum osteoprotegerin is associated with pulse pressure in kidney transplant recipients. Sci Rep 2015;5(1):14518.   DOI
6 Reinhard H, Lajer M, Gall MA, Tarnow L, Parving HH, Rasmussen LM, et al. Osteoprotegerin and mortality in type 2 diabetic patients. Diabetes Care 2010;33(12):2561-6.   DOI
7 Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, et al. osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 1998;12(9):1260-8.   DOI
8 Styrkarsdottir U, Halldorsson BV, Gretarsdottir S, Gudbjartsson DF, Walters GB, Ingvarsson T, et al. Multiple genetic loci for bone mineral density and fractures. N Engl J Med 2008;358(22):2355-65.   DOI
9 West SL, Lok CE, Jamal SA. Osteoprotegerin and fractures in men and women with chronic kidney disease. J Bone Miner Metab 2014;32(4):428-33.   DOI
10 Jorgensen L, Hansen JB, Ahmed L, Bjornerem A, Emaus N, Joakimsen R, et al. Osteoprotegerin is associated with hip fracture incidence: the Tromso Study. Int J Epidemiol 2012;41(4):1033-9.   DOI
11 Scialla JJ, Kao WH, Crainiceanu C, Sozio SM, Oberai PC, Shafi T, et al. Biomarkers of vascular calcification and mortality in patients with ESRD. Clin J Am Soc Nephrol 2014;9(4):745-55.   DOI
12 Speer G, Fekete BC, El Hadj Othmane T, Szabo T, Egresits J, Fodor E, et al. Serum osteoprotegerin level, carotid-femoral pulse wave velocity and cardiovascular survival in haemodialysis patients. Nephrol Dial Transplant 2008;23(10):3256-62.   DOI
13 Morena M, Dupuy AM, Jaussent I, Vernhet H, Gahide G, Klouche K, et al. A cut-off value of plasma osteoprotegerin level may predict the presence of coronary artery calcifications in chronic kidney disease patients. Nephrol Dial Transplant 2009;24(11):3389-97.   DOI
14 Meneghini M, Regalia A, Alfieri C, Barretta F, Croci D, Gandolfo MT, et al. Calcium and osteoprotegerin levels predict the progression of the abdominal aortic calcifications after kidney transplantation. Transplantation 2013;96(1):42-8.   DOI
15 Nascimento MM, Hayashi SY, Riella MC, Lindholm B. Elevated levels of plasma osteoprotegerin are associated with all-cause mortality risk and atherosclerosis in patients with stages 3 to 5 chronic kidney disease. Braz J Med Biol Res 2014;47(11):995-1002.   DOI
16 Kruzliak P, Berezin A, Kremzer A, Samura T, Benacka R, Mozos I, et al. Global longitudinal strain and strain rate in type two diabetes patients with chronic heart failure: relevance to osteoprotegerin. Folia Med (Plovdiv) 2016;58(3):164-73.   DOI
17 Lee JE, Kim HJ, Moon SJ, Nam JS, Kim JK, Kim SK, et al. Serum osteoprotegerin is associated with vascular stiffness and the onset of new cardiovascular events in hemodialysis patients. Korean J Intern Med 2013;28(6):668-77.   DOI
18 Kim BJ, Lee HA, Kim NH, Kim MW, Kim BS, Kang JH. The association of albuminuria, arterial stiffness, and blood pressure status in nondiabetic, nonhypertensive individuals. J Hypertens 2011;29(11):2091-8.   DOI
19 Vallee A, Yannoutsos A, Temmar M, Dreyfuss Tubiana C, Spinu I, Zhang Y, et al. Determinants of the aortic pulse wave velocity index in hypertensive and diabetic patients: predictive and therapeutic implications. J Hypertens 2018;36(12):2324-32.   DOI
20 Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol 2010;55(13):1318-27.   DOI
21 Berezin AE, Kremzer AA, Berezina TA, Martovitskaya YV, Gronenko EA. Data regarding association between serum osteoprotegerin level, numerous of circulating endothelial-derived and mononuclear-derived progenitor cells in patients with metabolic syndrome. Data Brief 2016;8:717-22.   DOI
22 Berezin AE, Kremzer AA, Samura TA, Berezina TA, Kruzliak P. Impaired immune phenotype of circulating endothelial-derived microparticles in patients with metabolic syndrome and diabetes mellitus. J Endocrinol Invest 2015;38(8):865-74.   DOI
23 Kim CS, Bae EH, Ma SK, Han SH, Choi KH, Lee J, et al. Association of serum osteoprotegerin levels with bone loss in chronic kidney disease: insights from the KNOW-CKD Study. PLoS One 2016;11(11):e0166792.   DOI
24 Morony S, Tintut Y, Zhang Z, Cattley RC, Van G, Dwyer D, et al. Osteoprotegerin inhibits vascular calcification without affecting atherosclerosis in ldlr(-/-) mice. Circulation 2008;117(3):411-20.   DOI
25 Schoppet M, Al-Fakhri N, Franke FE, Katz N, Barth PJ, Maisch B, et al. Localization of osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand, and receptor activator of nuclear factor-kappaB ligand in Monckeberg's sclerosis and atherosclerosis. J Clin Endocrinol Metab 2004;89(8):4104-12.   DOI
26 Chronic Kidney Disease Prognosis ConsortiumMatsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 2010;375(9731):2073-81.   DOI
27 Wu M, Rementer C, Giachelli CM. Vascular calcification: an update on mechanisms and challenges in treatment. Calcif Tissue Int 2013;93(4):365-73.   DOI
28 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):S1-130.
29 Rochette L, Meloux A, Rigal E, Zeller M, Cottin Y, Vergely C. The role of osteoprotegerin in the crosstalk between vessels and bone: Its potential utility as a marker of cardiometabolic diseases. Pharmacol Ther 2018;182:115-32.   DOI
30 Callegari A, Coons ML, Ricks JL, Rosenfeld ME, Scatena M. Increased calcification in osteoprotegerin-deficient smooth muscle cells: dependence on receptor activator of NF-${\kappa}B$ ligand and interleukin 6. J Vasc Res 2014;51(2):118-31.   DOI
31 Venuraju SM, Yerramasu A, Corder R, Lahiri A. Osteoprotegerin as a predictor of coronary artery disease and cardiovascular mortality and morbidity. J Am Coll Cardiol 2010;55(19):2049-61.   DOI
32 di Giuseppe R, Biemann R, Wirth J, Menzel J, Isermann B, Stangl GI, et al. Plasma osteoprotegerin, its correlates, and risk of heart failure: a prospective cohort study. Eur J Epidemiol 2017;32(2):113-23.   DOI
33 Zagura M, Serg M, Kampus P, Zilmer M, Zilmer K, Eha J, et al. Association of osteoprotegerin with aortic stiffness in patients with symptomatic peripheral artery disease and in healthy subjects. Am J Hypertens 2010;23(6):586-91.   DOI
34 Lee SW, Han SH, Yoo TH, Chung W, Park SK, Chae DW, et al. Relationship between brachial-ankle and heart-femoral pulse wave velocities and the rapid decline of kidney function. Sci Rep 2018;8(1):821.   DOI
35 Perez de Ciriza C, Moreno M, Restituto P, Bastarrika G, Simon I, Colina I, et al. Circulating osteoprotegerin is increased in the metabolic syndrome and associates with subclinical atherosclerosis and coronary arterial calcification. Clin Biochem 2014;47(18):272-8.   DOI
36 Avignon A, Sultan A, Piot C, Mariano-Goulart D, Thuan Dit Dieudonne JF, Cristol JP, et al. Osteoprotegerin: a novel independent marker for silent myocardial ischemia in asymptomatic diabetic patients. Diabetes Care 2007;30(11):2934-9.   DOI
37 Yilmaz MI, Siriopol D, Saglam M, Unal HU, Karaman M, Gezer M, et al. Osteoprotegerin in chronic kidney disease: associations with vascular damage and cardiovascular events. Calcif Tissue Int 2016;99(2):121-30.   DOI
38 Oh KH, Park SK, Park HC, Chin HJ, Chae DW, Choi KH, et al. KNOW-CKD (KoreaN cohort study for Outcome in patients With Chronic Kidney Disease): design and methods. BMC Nephrol 2014;15:80.   DOI
39 Munakata M. Brachial-ankle pulse wave velocity: background, method, and clinical evidence. Pulse (Basel) 2016;3(3-4):195-204.   DOI
40 Scialla JJ, Leonard MB, Townsend RR, Appel L, Wolf M, Budoff MJ, et al. Correlates of osteoprotegerin and association with aortic pulse wave velocity in patients with chronic kidney disease. Clin J Am Soc Nephrol 2011;6(11):2612-9.   DOI