Vascular calcification in chronic kidney disease mechanisms and clinical implications

Iranian Journal of Kidney Diseases

Volumn 5, Issue 5, 2011, Pages 285-299

  Ossareh, Shahrzad ^a  

^a IRAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

Author keywords

Calcium metabolism disorders; Cardiovascular diseases; Renal dialysis; Vascular diseases

Indexed keywords

BISPHOSPHONIC ACID DERIVATIVE; CALCITRIOL; CALCIUM; CINACALCET; FETUIN A; HYDROXYAPATITE; OSTEOCALCIN; OSTEOCLAST DIFFERENTIATION FACTOR; OSTEOGENIC PROTEIN 1; OSTEOPONTIN; OSTEOPROTEGERIN; PARATHYROID HORMONE; PARATHYROID HORMONE[1-34]; PHOSPHATE; PHOSPHATE BINDING AGENT; PLACEBO; PLASMA PROTEIN; PYROPHOSPHATE; SEVELAMER; SMAD6 PROTEIN; VITAMIN D; VITAMIN K GROUP;

ARTERY CALCIFICATION; BLOOD VESSEL CALCIFICATION; CARDIOVASCULAR RISK; CHRONIC KIDNEY DISEASE; CONTINUOUS AMBULATORY PERITONEAL DIALYSIS; CORONARY ARTERY ATHEROSCLEROSIS; CORONARY ARTERY CALCIFICATION; DOSE RESPONSE; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; ELECTRON BEAM TOMOGRAPHY; GENETIC SUSCEPTIBILITY; HEMODIALYSIS; HORMONE ACTION; HUMAN; KIDNEY FAILURE; LOW DRUG DOSE; MINERAL METABOLISM; MOLECULAR DYNAMICS; NONHUMAN; PATHOGENESIS; PREDICTION; PROTEIN PROTEIN INTERACTION; REVIEW; RISK FACTOR; SECONDARY HYPERPARATHYROIDISM; VITAMIN SUPPLEMENTATION;

CHRONIC DISEASE; HUMANS; KIDNEY DISEASES; KIDNEY FAILURE, CHRONIC; VASCULAR CALCIFICATION;

EID: 80052577149     PISSN: 17358582     EISSN: 17358604     Source Type: Journal    
DOI: None     Document Type: Review

References (154)

1. United States Renal Data System. Excerpts from USRDS 2009 Annual Data Report. U.S. Department of Health and Human Services. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Am J Kidney Dis. 2010;55:S1.
2. London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant. 2003;18:1731-1740.
3. 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.
4. Braun J, Oldendorf M, Moshage W, Heidler R, Zeitler E, Luft FC. Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients. Am J Kidney Dis. 1996;27:394-401.
5. Parfitt AM. Soft-tissue calcification in uremia. Arch Intern Med. 1969;124:544
6. Pollack VE, Schneider AF, Freund G, Kark RM. Chronic renal disease with secondary hyperparathyroidism. Arch Intern Med. 1959;103:200.
7. Milliner DS, Zinsmeister AR, Lieberman E, Landing B. Soft tissue calcification in pediatric patients with end-stage renal disease. Kidney Int. 1990;38:931-936
8. Oh J, Wunsch R, Turzer M, et al. Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure. Circulation. 2002;106:100-105.
9. Merjanian R, Budoff M, Adler S, Berman N, Mehrotra R. Coronary artery, aortic wall, and valvular calcification in nondialyzed individuals with type 2 diabetes and renal disease. Kidney Int. 2003;64:263-271.
10. Meema HE, Oreopoulos DG. Morphology, progression, and regression of arterial and periarterial calcifications in patients with end-stage renal disease. Radiology 1986;158:671-677.
11. Meema HE, Oreopoulos DG, Rapoport A. Serum magnesium level and arterial calcification in end-stage renal disease. Kidney Int. 1987;32:388-394.
12. Levey, AS, Beto, JA, Coronado, BE, et al. Controlling the epidemic of cardiovascular disease in chronic renal disease: what do we know? What do we need to learn? Where do we go from here? National Kidney Foundation Task Force on Cardiovascular Disease. Am J Kidney Dis. 1998;32:853.
13. Contiguglia SR, Alfrey AC, Miller NL, Runnells DE, Le Geros RZ. Nature of soft tissue calcification in uremia. Kidney Int. 1973;4:229-235
14. Reid JD, Andersen ME. Medial calcification (whitlockite) in the aorta. Atherosclerosis. 1993;101:213-224.
15. Stary HC. Lipid and macrophage accumulations in arteries of children and the development of atherosclerosis. Am J Clin Nutr. 2000;72:1297S-1306S.
16. Shanahan CM, Cary NR, Salisbury JR, Proudfoot D, Weissberg PL, Edmonds ME. Medial localization of mineralization-regulating proteins in association with Mönckeberg's sclerosis: evidence for smooth muscle cell-mediated vascular calcification. Circulation. 1999;100:2168-2176.
17. Proudfoot D, Davies JD, Skepper JN, Weissberg PL, Shanahan CM. Acetylated low-density lipoprotein stimulates human vascular smooth muscle cell calcification by promoting osteoblastic differentiation and inhibiting phagocytosis. Circulation. 2002;106:3044-3050.
18. Lanzer P. [Mönckeberg media calcinosis]. Z Kardiol. 1998;87:586-593. German.
19. Proudfoot D, Shanahan CM. Biology of calcification in vascular cells: intima versus media. Herz. 2001;26: 245-51.
20. Shroff RC, Shanahan CM. The vascular biology of calcification. Semin Dial. 2007;20:103-109.
21. Giachelli CM. Vascular calcification mechanisms. J Am Soc Nephrol. 2004;15:2959-64.
22. Ivandic BT, Qiao JH, Machleder D, Liao F, Drake TA, Lusis AJ. A locus on chromosome 7 determines myocardial cell necrosis and calcification (dystrophic cardiac calcinosis) in mice. Proc Natl Acad Sci U S A. 1996;93:5483-5488.
23. Ivandic BT, Utz HF, Kaczmarek PM, et al. New Dyscalc loci for myocardial cell necrosis and calcification (dystrophic cardiac calcinosis) in mice. Physiol Genomics. 2001;6:137-44.
24. Colinayo VV, Qiao JH, Demant P, Krass K, Lusis AJ, Drake TA. Genetic characterization of the Dyscalc locus. Mamm Genome. 2002;13:283-288.
25. Matsui Y, Rittling SR, Okamoto H, et al. Osteopontin deficiency attenuates atherosclerosis in female apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2003;23:1029-1034.
26. Pan JH, Sukhova GK, Yang JT, et al. Macrophage migration inhibitory factor deficiency impairs atherosclerosis in low-density lipoprotein receptordeficient mice. Circulation. 2004;109:3149-3153.
27. Luo G, Ducy P, McKee MD, et al. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature. 1997;386:78-81.
28. Speer MY, Chien YC, Quan M, et al. Smooth muscle cells deficient in osteopontin have enhanced susceptibility to calcification in vitro. Cardiovasc Res. 2005;66:324-333.
29. Kuro-o M, Matsumura Y, Aizawa H, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997;390:45-51
30. Spicer SS, Lewis SE, Tashian RE, Schulte BA. Mice carrying a CAR-2 null allele lack carbonic anhydrase II immunohistochemically and show vascular calcification. Am J Pathol. 1989;134:947-954.
31. Schafer C, Heiss A, Schwarz A, et al. The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest. 2003;112:357-366.
32. Musunuru K, Post WS, Herzog W, et al. Association of single nucleotide polymorphisms on chromosome 9p21.3 with platelet reactivity: a potential mechanism for increased vascular disease. Circ Cardiovasc Genet. 2010;3:445-453
33. Burdon KP, Rudock ME, Lehtinen AB, et al. Human lipoxygenase pathway gene variation and association with markers of subclinical atherosclerosis in the diabetes heart study. Mediators Inflamm.;2010:170153.
34. Schmitz F, Ewering S, Zerres K, Klomfass S, Hoffmann R, Ortlepp JR. Parathyroid hormone gene variant and calcific aortic stenosis. J Heart Valve Dis. 2009;18:262-267.
35. Freedman BI, Bowden DW, Ziegler JT, et al. Bone morphogenetic protein 7 (BMP7) gene polymorphisms are associated with inverse relationships between vascular calcification and BMD: the Diabetes Heart Study. J Bone Miner Res. 2009;24:1719-1727.
36. Pfohl M, Athanasiadis A, Koch M, et al. Insertion/ deletion polymorphism of the angiotensin I-converting enzyme gene is associated with coronary artery plaque calcification as assessed by intravascular ultrasound. J Am Coll Cardiol 1998;31:987-991.
37. Narayan KM, Pettitt DJ, Hanson RL, et al. Familial aggregation of medial arterial calcification in Pima Indians with and without diabetes. Diabetes Care 1996;19:968-971
38. Wagenknecht LE, Bowden DW, Carr JJ, Langefeld CD, Freedman BI, Rich SS. Familial aggregation of coronary artery calcium in families with type 2 diabetes. Diabetes. 2001;50:861-866.
39. Wang Y, Zhang W, Zhang Y, et al. VKORC1 haplotypes are associated with arterial vascular diseases (stroke, coronary heart disease, and aortic dissection). Circulation. 2006;113:1615-1621.
40. Rufino M, Hernández D, Barrios Y, Salido E. The GLUT-1 XbaI gene polymorphism is associated with vascular calcifications in nondiabetic uremic patients. Nephron Clin Pract. 2008;108:182-187.
41. Giachelli CM. Mechanisms of vascular calcification in uremia. Semin Nephrol. 2004;24:401-402.
42. El-Abbadi MM, Pai AS, Leaf EM, et al. Phosphate feeding induces arterial medial calcification in uremic mice: role of serum phosphorus, fibroblast growth factor-23, and osteopontin. Kidney Int. 2009;75:1297-1307.
43. Goodman WG, Goldin J, Kuizon BD, et al. Coronaryartery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med. 2000;342:1478-1483.
44. Chertow GM, Raggi P, Chasan-Taber S, Bommer J, Holzer H, Burke SK. Determinants of progressive vascular calcification in haemodialysis patients. Nephrol Dial Transplant. 2004;19:1489-1496.
45. Phan O, Ivanovski O, Nikolov IG, et al. Effect of oral calcium carbonate on aortic calcification in apolipoprotein E-deficient (apoE-/-) mice with chronic renal failure. Nephrol Dial Transplant. 2008;23:82-90.
46. Ossareh S, Alaei A, Saedi D. Carotid intima-media thickness in maintenance hemodialysis patients: role of cardiovascular risk factor. Iran J Kidney Dis. 2011;5: 169-174.
47. Block GA, Spiegel DM, Ehrlich J, et al. Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney Int. 2005;68: 1815-1824.
48. Mathew S, Lund RJ, Strebeck F, Tustison KS, Geurs T, Hruska KA. Reversal of the adynamic bone disorder and decreased vascular calcification in chronic kidney disease by sevelamer carbonate therapy. J Am Soc Nephrol. 2007;18:122-130.
49. Asmus HG, Braun J, Krause R, et al. Two year comparison of sevelamer and calcium carbonate effects on cardiovascular calcification and bone density. Nephrol Dial Transplant. 2005;20:1653-1661.
50. Covic A, Kanbay M, Voroneanu L, et al. Vascular calcification in chronic kidney disease. Clin Sci (Lond). 2010;119:111-121.
51. Yang H, Curinga G, Giachelli CM. Elevated extracellular calcium levels induce smooth muscle cell matrix mineralization in vitro. Kidney Int. 2004;66:2293-2299.
52. Shioi A, Nishizawa Y. [Roles of hyperphosphatemia in vascular calcification]. Clin Calcium. 2009;19:180-185. Japanese.
53. Adragao T, Pires A, Lucas C, et al. A simple vascular calcification score predicts cardiovascular risk in haemodialysis patients. Nephrol Dial Transplant. 2004;19:1480-1488.
54. Oh J, Wunsch R, Turzer M, et al. Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure. Circulation. 2002;106:100-105.
55. Kraśniak A, Drozdz M, Pasowicz M, et al. Factors involved in vascular calcification and atherosclerosis in maintenance haemodialysis patients. Nephrol Dial Transplant. 2007;22:515-521.
56. Goldsmith DJ, Covic A, Sambrook PA, Ackrill P. Vascular calcification in long-term haemodialysis patients in a single unit: a retrospective analysis. Nephron. 1997;77:37-43.
57. Shao JS, Cheng SL, Charlton-Kachigian N, Loewy AP, Towler DA. Teriparatide (human parathyroid hormone (1-34)) inhibits osteogenic vascular calcification in diabetic low density lipoprotein receptor-deficient mice. J Biol Chem. 2003;278:50195-50202.
58. Shanahan CM. Mechanisms of vascular calcification in renal disease. Clin Nephrol. 2005;63:146-157.
59. Martola L, Barany P, Stenvinkel P. Why do dialysis patients develop a heart of stone and bone of china? Blood Purif. 2005;23:203-210.
60. Razzaque MS. The dualistic role of vitamin D in vascular calcifications. Kidney Int. 2011;79:708-714.
61. Zehnder D, Bland R, Chana RS, et al. Synthesis of 1,25-dihydroxyvitamin D(3) by human endothelial cells is regulated by inflammatory cytokines: a novel autocrine determinant of vascular cell adhesion. Am Soc Nephrol. 2002;13:621-629.
62. Watson KE, Abrolat ML, Malone LL, et al. Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation. 1997;96:1755-1760.
63. Braam LA, Hoeks AP, Brouns F, Hamulyák K, Gerichhausen MJ, Vermeer C. Beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women: a follow-up study. Thromb Haemost. 2004;91:373-380.
64. Briese S, Wiesner S, Will JC, et al. Arterial and cardiac disease in young adults with childhood-onset end-stage renal disease-impact of calcium and vitamin D therapy. Nephrol Dial Transplant. 2006;21:1906-1914.
65. McCullough PA, Sandberg KR, Dumler F, Yanez JE. Determinants of coronary vascular calcification in patients with chronic kidney disease and end-stage renal disease: a systematic review. Nephrol. 2004 Mar-;17:205-215.
66. Henley C, Colloton M, Cattley RC, et al. 1,25-Dihydroxyvitamin D3 but not cinacalcet HCl (Sensipar/Mimpara) treatment mediates aortic calcification in a rat model of secondary hyperparathyroidism. Nephrol Dial Transplant. 2005;20:1370-1377
67. Haffner D, Hocher B, Müller D, et al. Systemic cardiovascular disease in uremic rats induced by 1,25(OH)2D3. J Hypertens. 2005;23:1067-1075.
68. Memon F, El-Abbadi M, Nakatani T, Taguchi T, Lanske B, Razzaque MS. Does Fgf23-klotho activity influence vascular and soft tissue calcification through regulating mineral ion metabolism? Kidney Int. 2008;74:566-570.
69. Razzaque MS, Lanske B. Hypervitaminosis D and premature aging: lessons learned from Fgf23 and Klotho mutant mice. Trends Mol Med. 2006;12:298-305.
70. Shroff R, Egerton M, Bridel M, et al. A bimodal association of vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol. 2008;19:1239-1246.
71. Abedin M, Tintut Y, Demer LL. Vascular calcification: mechanisms and clinical ramifications. Arterioscler Thromb Vasc Biol. 2004;24:1161-1170
72. Giachelli C, Bae N, Lombardi D, Majesky M, Schwartz S. Molecular cloning and characterization of 2B7, a rat mRNA which distinguishes smooth muscle cell phenotypes in vitro and is identical to osteopontin (secreted phosphoprotein I, 2aR). Biochem Biophys Res Commun. 1991;177:867-873.
73. Boström K, Watson KE, Horn S, Wortham C, Herman IM, Demer LL. Bone morphogenetic protein expression in human atherosclerotic lesions. J Clin Invest. 1993;91:1800-1809.
74. Shanahan CM, Cary NR, Metcalfe JC, Weissberg PL. High expression of genes for calcification-regulating proteins in human atherosclerotic plaques. J Clin Invest. 1994;93:2393-2402.
75. Rennenberg RJ, Schurgers LJ, Kroon AA, Stehouwer CD. Arterial calcifications. J Cell Mol Med. 2010;14:2203-2210.
76. Steitz SA, Speer MY, Curinga G, et al. Smooth muscle cell phenotypic transition associated with calcification: upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circ Res. 2001;89:1147-1154.
77. Chamley-Campbell J, Campbell GR, Ross R. The smooth muscle cell in culture. Physiol Rev. 1979;59:1-61.
78. Chamley-Campbell JH, Campbell GR, Ross R. Phenotype-dependent response of cultured aortic smooth muscle to serum mitogens. J Cell Biol. 1981;89:379-383.
79. Weissberg PL, Clesham GJ, Bennett MR. Is vascular smooth muscle cell proliferation beneficial? Lancet. 1996;347(8997):305-307.
80. Iyemere VP, Proudfoot D, Weissberg PL, Shanahan CM. Vascular smooth muscle cell phenotypic plasticity and the regulation of vascular calcification. J Intern Med. 2006;260:192-210.
81. King KE, Iyemere VP, Weissberg PL, Shanahan CM. Krüppel-like factor 4 (KLF4/GKLF) is a target of bone morphogenetic proteins and transforming growth factor beta 1 in the regulation of vascular smooth muscle cell phenotype. J Biol Chem. 2003;278:11661-11669.
82. Anderson HC. Molecular biology of matrix vesicles. Clin Orthop Relat Res. 1995;:266-280.
83. Kim KM. Calcification of matrix vesicles in human aortic valve and aortic media. Fed Proc. 1976;35:156-162.
84. Reynolds JL, Joannides AJ, Skepper JN, et al. Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: a potential mechanism for accelerated vascular calcification in ESRD. J Am Soc Nephrol. 2004;15:2857-2867.
85. Isner JM, Kearney M, Bortman S, Passeri J. Apoptosis in human atherosclerosis and restenosis. Circulation. 1995;91:2703-2711.
86. Kockx MM, De Meyer GR, Muhring J, Jacob W, Bult H, Herman AG. Apoptosis and related proteins in different stages of human atherosclerotic plaques. Circulation. 1998;97:2307-2315.
87. Geng YJ, Libby P. Evidence for apoptosis in advanced human atheroma. Colocalization with interleukin-1 betaconverting enzyme. Am J Pathol. 1995;147:251-66.
88. Proudfoot D, Skepper JN, Hegyi L, Bennett MR, Shanahan CM, Weissberg PL. Apoptosis regulates human vascular calcification in vitro: evidence for initiation of vascular calcification by apoptotic bodies. Circ Res. 2000;87:1055-1062.
89. Littlewood TD, Bennett MR. Apoptotic cell death in atherosclerosis. Curr Opin Lipidol. 2003;14:469-475.
90. Kim HH, Kim K. Enhancement of TNF-alpha-mediated cell death in vascular smooth muscle cells through cytochrome c-independent pathway by the proteasome inhibitor. FEBS Lett. 2003;535:190-194.
91. Kockx MM. Apoptosis in the atherosclerotic plaque: quantitative and qualitative aspects. Arterioscler Thromb Vasc Biol. 1998;18:1519-1522.
92. Price PA, Urist MR, Otawara Y. Matrix Gla protein, a new gamma-carboxyglutamic acid-containing protein which is associated with the organic matrix of bone. Biochem Biophys Res Commun. 1983;117:765-771.
93. Boström K, Tsao D, Shen S, Wang Y, Demer LL. Matrix GLA protein modulates differentiation induced by bone morphogenetic protein-2 in C3H10T1/2 cells. J Biol Chem. 2001;276:14044-14052.
94. Luo G, Ducy P, McKee MD, et al. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature. 1997;386:78-81.
95. Krueger T, Westenfeld R, Schurgers L, Brandenburg V. Coagulation meets calcification: the vitamin K system. Int J Artif Organs. 2009;32:67-74.
96. Moe SM, Chen NX. Pathophysiology of vascular calcification in chronic kidney disease. Circ Res. 2004;95:560-567.
97. Schlieper G, Westenfeld R, Krüger T, et al. Circulating nonphosphorylated carboxylated matrix gla protein predicts survival in ESRD. J Am Soc Nephrol. 2011;22:387-395.
98. Giachelli CM, Schwartz SM, Liaw L. Molecular and cellular biology of osteopontin: potential role in cardiovascular disease. Trends Cardiovasc Med. 1995;5:88-95.
99. Wada T, McKee MD, Steitz S, Giachelli CM. Calcification of vascular smooth muscle cell cultures: inhibition by osteopontin. Circ Res. 1999;84:166-178.
100. Ohmori R, Momiyama Y, Taniguchi H, et al. Plasma osteopontin levels are associated with the presence and extent of coronary artery disease. Atherosclerosis. 2003;170:333-337.
101. Asou Y, Rittling SR, Yoshitake H, et al. Osteopontin facilitates angiogenesis, accumulation of osteoclasts, and resorption in ectopic bone. Endocrinology. 2001;142: 1325-1332.
102. Lebreton JP, Joisel F, Raoult JP, Lannuzel B, Rogez JP, Humbert G. Serum concentration of human alpha 2 HS glycoprotein during the inflammatory process: evidence that alpha 2 HS glycoprotein is a negative acute-phase reactant. J Clin Invest. 1979;64:1118-1129.
103. Ketteler M. Fetuin-A and extraosseous calcification in uremia. Curr Opin Nephrol Hypertens. 2005;14:337-342.
104. Heiss A, DuChesne A, Denecke B, et al. Structural basis of calcification inhibition by alpha 2-HS glycoprotein/ fetuin-A. Formation of colloidal calciprotein particles. J Biol Chem. 2003;278:13333-13341.
105. Stompór T. An overview of the pathophysiology of vascular calcification in chronic kidney disease. Perit Dial Int. 2007;27 Suppl 2:215-222.
106. Ketteler M, Bongartz P, Westenfeld R, et al. Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a crosssectional study. Lancet. 2003;361:827-833.
107. Honda H, Qureshi AR, Heimbürger O, et al. Serum albumin, C-reactive protein, interleukin 6, and fetuin a as predictors of malnutrition, cardiovascular disease, and mortality in patients with ESRD. Am J Kidney Dis. 2006;47:139-148.
108. Stenvinkel P, Wang K, Qureshi AR, et al. Low fetuin-A levels are associated with cardiovascular death: Impact of variations in the gene encoding fetuin. Kidney Int. 2005;67:2383-2392.
109. Simonet WS, Lacey DL, Dunstan CR, et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997;89:309-319.
110. Schoppet M, Preissner KT, Hofbauer LC. RANK ligand and osteoprotegerin: paracrine regulators of bone metabolism and vascular function. Arterioscler Thromb Vasc Biol. 2002;22:549-553.
111. Price PA, June HH, Buckley JR, Williamson MK. Osteoprotegerin inhibits artery calcification induced by warfarin and by vitamin D. Arterioscler Thromb Vasc Biol. 2001;21:1610-1616.
112. Jono S, Ikari Y, Shioi A, et al. Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation. 2002;106:1192-1194.
113. Nitta K, Akiba T, Uchida K, et al. The progression of vascular calcification and serum osteoprotegerin levels in patients on long-term hemodialysis. Am J Kidney Dis. 2003;42:303-309.
114. Van Campenhout A, Golledge J. Osteoprotegerin, vascular calcification and atherosclerosis. Atherosclerosis. 2009;204:321-329.
115. Morena M, Terrier N, Jaussent I, et al. Plasma osteoprotegerin is associated with mortality in hemodialysis patients. J Am Soc Nephrol. 2006;17: 262-270.
116. Davies MR, Lund RJ, Hruska KA. BMP-7 is an efficacious treatment of vascular calcification in a murine model of atherosclerosis and chronic renal failure. J Am Soc Nephrol. 2003;14:1559-1567.
117. Galvin KM, Donovan MJ, Lynch CA, et al. A role for smad6 in development and homeostasis of the cardiovascular system. Nat Genet. 2000;24:171-174.
118. Lomashvili KA, Cobbs S, Hennigar RA, Hardcastle KI, O'Neill WC. Phosphate-induced vascular calcification: role of pyrophosphate and osteopontin. J Am Soc Nephrol. 2004;15:1392-1401.
119. Lomashvili KA, Khawandi W, O'Neill WC. Reduced plasma pyrophosphate levels in hemodialysis patients. J Am Soc Nephrol. 2005;16:2495-2500.
120. Rachow JW, Ryan LM. Inorganic pyrophosphate metabolism in arthritis. Rheum Dis Clin North Am. 1988;14:289-302.
121. Witteman JC, Kok FJ, van Saase JL, Valkenburg HA. Aortic calcification as a predictor of cardiovascular mortality. Lancet. 1986;2:1120-1122.
122. Rodondi N, Taylor BC, Bauer DC, et al. Association between aortic calcification and total and cardiovascular mortality in older women. J Intern Med. 2007;261:238-244.
123. Rennenberg RJ, Kessels AG, Schurgers LJ, van Engelshoven JM, de Leeuw PW, Kroon AA. Vascular calcifications as a marker of increased cardiovascular risk: a meta-analysis. Vasc Health Risk Manag. 2009;5:185-197.
124. Blacher J, Safar ME, Pannier B, Guerin AP, Marchais SJ, London GM. Prognostic significance of arterial stiffness measurements in end-stage renal disease patients. Curr Opin Nephrol Hypertens. 2002;11:629-634.
125. Guérin AP, Pannier B, Marchais SJ, London GM. Cardiovascular disease in the dialysis population: prognostic significance of arterial disorders. Curr Opin Nephrol Hypertens. 2006;15:105-110.
126. London GM. Cardiovascular calcifications in uremic patients: clinical impact on cardiovascular function. J Am Soc Nephrol. 2003;14:305-309.
127. London GM, Marchais SJ, Guerin AP. Arterial stiffness and function in end-stage renal disease. Adv Chronic Kidney Dis. 2004;11:202-209.
128. Safar ME, Blacher J, Pannier B, et al. Central pulse pressure and mortality in end-stage renal disease. Hypertension. 2002;39:735-738.
129. Guerin AP, Blacher J, Pannier B, Marchais SJ, Safar ME, London GM. Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure. Circulation. 2001;103:987-992.
130. DeLoach SS, Joffe MM, Mai X, Goral S, Rosas SE. Aortic calcification predicts cardiovascular events and all-cause mortality in renal transplantation. Nephrol Dial Transplant. 2009;24:1314-1319.
131. Junyent M, Martínez M, Borràs M, et al. Predicting cardiovascular disease morbidity and mortality in chronic kidney disease in Spain. The rationale and design of NEFRONA: a prospective, multicenter, observational cohort study. BMC Nephrol. 2010;11:14.
132. Braun J, Oldendorf M, Moshage W, Heidler R, Zeitler E, Luft FC. Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients. Am J Kidney Dis. 1996;27:394-401.
133. Blacher J, Asmar R, Djane S, London GM, Safar ME. Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension. 1999;33: 1111-1117.
134. Persson J, Formgren J, Israelsson B, Berglund G. Ultrasound-determined intima-media thickness and atherosclerosis. Direct and indirect validation. Arterioscler Thromb. 1994;14:261-264.
135. 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.
136. Bellasi A, Ferramosca E, Muntner P, et al. Correlation of simple imaging tests and coronary artery calcium measured by computed tomography in hemodialysis patients. Kidney Int. 2006;70:1623-1628.
137. Wang AY, Wang M, Woo J, et al. Cardiac valve calcification as an important predictor for all-cause mortality and cardiovascular mortality in long-term peritoneal dialysis patients: a prospective study. J Am Soc Nephrol. 2003;14:159-618.
138. 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;:1-130.
139. Goldsmith D. The case against routine screening for vascular calcification in chronic kidney disease. Semin Dial. 2010;23:280-282.
140. Uhlig K. There is no practical utility in routinely screening dialysis patients for vascular calcification. Semin Dial. 2010;23:277-279.
141. London GM, Marchais SJ, Guérin AP, Boutouyrie P, Métivier F, de Vernejoul MC. Association of bone activity, calcium load, aortic stiffness, and calcifications in ESRD. J Am Soc Nephrol. 2008;19:1827-1835.
142. Barreto DV, Barreto Fde C, Carvalho AB, et al. Association of changes in bone remodeling and coronary calcification in hemodialysis patients: a prospective study. Am J Kidney Dis. 2008;52:1139-1150.
143. Phan O, Ivanovski O, Nguyen-Khoa T, et al. Sevelamer prevents uremia-enhanced atherosclerosis progression in apolipoprotein E-deficient mice. Circulation. 2005;112:2875-2882.
144. Chertow GM, Burke SK, Raggi P; Treat to Goal Working Group. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int. 2002;62:245-252.
145. Ferramosca E, Burke S, Chasan-Taber S, Ratti C, Chertow GM, Raggi P. Potential antiatherogenic and anti-inflammatory properties of sevelamer in maintenance hemodialysis patients. Am Heart J. 2005;149:820-825.
146. Suki WN; Dialysis Clinical Outcomes Revisited Investigators. Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients: results of a randomized clinical trial. J Ren Nutr. 2008;18:91-98.
147. Tonelli M, Wiebe N, Culleton B, et al; Alberta Kidney Disease Network. Systematic review of the clinical efficacy and safety of sevelamer in dialysis patients. Nephrol Dial Transplant. 2007;22:2856-2866.
148. Cunningham J, Danese M, Olson K, Klassen P, Chertow GM. Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism. Kidney Int. 2005;68:1793-1800.
149. Raggi P, Chertow GM, Torres PU, et al; On behalf of the ADVANCE Study Group. The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcification in patients on hemodialysis. Nephrol Dial Transplant. 2011;26:1327-1339.
150. Clinicaltrials.gov [homepage on the internet]. EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events. Available from: http://clinicaltrials.gov/ct2/show/NCT00345839
151. Price PA, Faus SA, Williamson MK. Bisphosphonates alendronate and ibandronate inhibit artery calcification at doses comparable to those that inhibit bone resorption. Arterioscler Thromb Vasc Biol. 2001;21:817-824.
152. Nitta K, Akiba T, Suzuki K, et al. Effects of cyclic intermittent etidronate therapy on coronary artery calcification in patients receiving long-term hemodialysis. Am J Kidney Dis. 2004;44:680-688.
153. Toussaint ND, Elder GJ, Kerr PG. Bisphosphonates in chronic kidney disease; balancing potential benefits and adverse effects on bone and soft tissue. Clin J Am Soc Nephrol. 2009;4:221-233.
154. Westenfeld R, Ketteler M, Brandenburg VM. Anti-RANKL therapy-implications for the bone-vascular-axis in CKD? Denosumab in post-menopausal women with low bone mineral density. Nephrol Dial Transplant. 2006;21:2075-2077.