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Vascular calcification in chronic kidney disease

Behdad Afzali, MRCP, PhD, PGDip, FHEA, MAcadMEd
David JA Goldsmith, MA, FRCP
Section Editor
Stanley Goldfarb, MD
Deputy Editor
Alice M Sheridan, MD


The most common cause of death in dialysis patients is cardiovascular disease (CVD). This may be due in part to excess vascular calcification (VC), particularly coronary artery calcification (CAC), which can be observed even in very young dialysis patients [1-5]. Calcium can be deposited into either the medial or intimal layers of the vasculature.

The epidemiology, detection, and clinical significance of VC for patients with chronic kidney disease (CKD) are discussed in this topic review. The definition, pathogenesis, and molecular biology of VC are discussed separately. (See "Biology of vascular calcification in chronic kidney disease".)

The treatment of hyperphosphatemia and hyperparathyroidism associated with CKD and other issues associated with mineral and bone disease associated with CKD are also discussed elsewhere. (See "Treatment of hyperphosphatemia in chronic kidney disease" and "Management of secondary hyperparathyroidism and mineral metabolism abnormalities in adult predialysis patients with chronic kidney disease" and "Management of secondary hyperparathyroidism and mineral metabolism abnormalities in dialysis patients" and "Overview of chronic kidney disease-mineral bone disease (CKD-MBD)" and "Adynamic bone disease associated with chronic kidney disease".)


Calcification in association with atherosclerosis is not a new phenomenon. The Horus study revealed atherosclerosis in 34 percent of mummies from four geographical regions or populations that spanned over 4000 years [6]. In ancient times, the prevalence of atherosclerosis may have been due not only to dietary factors, but also to chronic infection-inflammation. Calcification may be considered a classical response to injury to endothelium and smooth muscle layers.

The prevalence of VC among patients with CKD, especially those on dialysis, is extremely high. The prevalence of VC detected by computed tomographic (CT) scanning is >80 percent among dialysis patients [1-3,7-22]. The reported prevalence among CKD patients who are not on dialysis is 47 to 83 percent [21,23-28]. The prevalence is generally the highest among individuals with lower estimated glomerular filtration rates (eGFRs). Among patients with reduced eGFR <60 mL/min per 1.73 m2, calcification is more prevalent, more severe, and progresses at a faster rate than in the general population. By contrast, among patients who have GFR ≥60 mL/min per 1.73 m2 who have moderately increased albuminuria (formerly called "microalbuminuria"), the risk is the same as among patients without CKD [24,25].


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Literature review current through: Sep 2016. | This topic last updated: Sep 5, 2014.
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  1. Braun J, Oldendorf M, Moshage W, et al. Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients. Am J Kidney Dis 1996; 27:394.
  2. Goodman WG, Goldin J, Kuizon BD, et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000; 342:1478.
  3. 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.
  4. London GM, Guérin AP, Marchais SJ, et al. Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 2003; 18:1731.
  5. Sigrist MK, Taal MW, Bungay P, McIntyre CW. Progressive vascular calcification over 2 years is associated with arterial stiffening and increased mortality in patients with stages 4 and 5 chronic kidney disease. Clin J Am Soc Nephrol 2007; 2:1241.
  6. Thompson RC, Allam AH, Lombardi GP, et al. Atherosclerosis across 4000 years of human history: the Horus study of four ancient populations. Lancet 2013; 381:1211.
  7. Meema HE, Oreopoulos DG, deVeber GA. Arterial calcifications in severe chronic renal disease and their relationship to dialysis treatment, renal transplant, and parathyroidectomy. Radiology 1976; 121:315.
  8. Meema HE, Oreopoulos DG. Morphology, progression, and regression of arterial and periarterial calcifications in patients with end-stage renal disease. Radiology 1986; 158:671.
  9. Meema HE, Oreopoulos DG, Rapoport A. Serum magnesium level and arterial calcification in end-stage renal disease. Kidney Int 1987; 32:388.
  10. Andresen JH, Nielsen HE. [Extraskeletal calcification in chronic renal failure during hemodialysis and after renal transplantation (author's transl)]. Klin Wochenschr 1982; 60:199.
  11. 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.
  12. 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. J Nephrol 2004; 17:205.
  13. Schwaiger JP, Neyer U, Sprenger-Mähr H, et al. A simple score predicts future cardiovascular events in an inception cohort of dialysis patients. Kidney Int 2006; 70:543.
  14. Tamashiro M, Iseki K, Sunagawa O, et al. Significant association between the progression of coronary artery calcification and dyslipidemia in patients on chronic hemodialysis. Am J Kidney Dis 2001; 38:64.
  15. 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.
  16. Stompór T, Pasowicz M, Sulłowicz W, et al. An association between coronary artery calcification score, lipid profile, and selected markers of chronic inflammation in ESRD patients treated with peritoneal dialysis. Am J Kidney Dis 2003; 41:203.
  17. Eifinger F, Wahn F, Querfeld U, et al. Coronary artery calcifications in children and young adults treated with renal replacement therapy. Nephrol Dial Transplant 2000; 15:1892.
  18. Raggi P, Boulay A, Chasan-Taber S, et al. Cardiac calcification in adult hemodialysis patients. A link between end-stage renal disease and cardiovascular disease? J Am Coll Cardiol 2002; 39:695.
  19. Moe SM, O'Neill KD, Fineberg N, et al. Assessment of vascular calcification in ESRD patients using spiral CT. Nephrol Dial Transplant 2003; 18:1152.
  20. Sharples EJ, Pereira D, Summers S, et al. Coronary artery calcification measured with electron-beam computerized tomography correlates poorly with coronary artery angiography in dialysis patients. Am J Kidney Dis 2004; 43:313.
  21. Merjanian R, Budoff M, Adler S, et al. Coronary artery, aortic wall, and valvular calcification in nondialyzed individuals with type 2 diabetes and renal disease. Kidney Int 2003; 64:263.
  22. Matsuoka M, Iseki K, Tamashiro M, et al. Impact of high coronary artery calcification score (CACS) on survival in patients on chronic hemodialysis. Clin Exp Nephrol 2004; 8:54.
  23. 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; :S1.
  24. Kramer H, Toto R, Peshock R, et al. Association between chronic kidney disease and coronary artery calcification: the Dallas Heart Study. J Am Soc Nephrol 2005; 16:507.
  25. Qunibi WY, Abouzahr F, Mizani MR, et al. Cardiovascular calcification in Hispanic Americans (HA) with chronic kidney disease (CKD) due to type 2 diabetes. Kidney Int 2005; 68:271.
  26. Russo D, Palmiero G, De Blasio AP, et al. Coronary artery calcification in patients with CRF not undergoing dialysis. Am J Kidney Dis 2004; 44:1024.
  27. Chiu YW, Adler SG, Budoff MJ, et al. Coronary artery calcification and mortality in diabetic patients with proteinuria. Kidney Int 2010; 77:1107.
  28. Ix JH, Katz R, Kestenbaum B, et al. Association of mild to moderate kidney dysfunction and coronary calcification. J Am Soc Nephrol 2008; 19:579.
  29. 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.
  30. POLLAK VE, SCHNEIDER AF, FREUND G, KARK RM. Chronic renal disease with secondary hyperparathyroidism. AMA Arch Intern Med 1959; 103:200.
  31. Parfitt AM. Soft-tissue calcification in uremia. Arch Intern Med 1969; 124:544.
  32. Kuzela DC, Huffer WE, Conger JD, et al. Soft tissue calcification in chronic dialysis patients. Am J Pathol 1977; 86:403.
  33. Terman DS, Alfrey AC, Hammond WS, et al. Cardiac calcification in uremia. A clinical, biochemical and pathologic study. Am J Med 1971; 50:744.
  34. Ibels LS, Alfrey AC, Huffer WE, et al. Arterial calcification and pathology in uremic patients undergoing dialysis. Am J Med 1979; 66:790.
  35. Milliner DS, Zinsmeister AR, Lieberman E, Landing B. Soft tissue calcification in pediatric patients with end-stage renal disease. Kidney Int 1990; 38:931.
  36. Massy ZA, Drüeke TB. Vascular calcification. Curr Opin Nephrol Hypertens 2013; 22:405.
  37. O'Neill WC, Lomashvili KA, Malluche HH, et al. Treatment with pyrophosphate inhibits uremic vascular calcification. Kidney Int 2011; 79:512.
  38. Hill KM, Martin BR, Wastney ME, et al. Oral calcium carbonate affects calcium but not phosphorus balance in stage 3-4 chronic kidney disease. Kidney Int 2013; 83:959.
  39. Evenepoel P, Wolf M. A balanced view of calcium and phosphate homeostasis in chronic kidney disease. Kidney Int 2013; 83:789.
  40. Ganesh SK, Stack AG, Levin NW, et al. Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patients. J Am Soc Nephrol 2001; 12:2131.
  41. Coladonato JA, Szczech LA, Friedman EA, Owen WF Jr. Does calcium kill ESRD patients--the skeptic's perspective. Nephrol Dial Transplant 2002; 17:229.
  42. Chertow GM, Raggi P, Chasan-Taber S, et al. Determinants of progressive vascular calcification in haemodialysis patients. Nephrol Dial Transplant 2004; 19:1489.
  43. 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.
  44. Chertow GM, Burke SK, Dillon MA, Slatopolsky E. Long-term effects of sevelamer hydrochloride on the calcium x phosphate product and lipid profile of haemodialysis patients. Nephrol Dial Transplant 1999; 14:2907.
  45. Burke SK, Dillon MA, Hemken DE, et al. Meta-analysis of the effect of sevelamer on phosphorus, calcium, PTH, and serum lipids in dialysis patients. Adv Ren Replace Ther 2003; 10:133.
  46. Katopodis KP, Andrikos EK, Gouva CD, et al. Sevelamer hydrochloride versus aluminum hydroxide: effect on serum phosphorus and lipids in CAPD patients. Perit Dial Int 2006; 26:320.
  47. Ferramosca E, Burke S, Chasan-Taber S, et al. Potential antiatherogenic and anti-inflammatory properties of sevelamer in maintenance hemodialysis patients. Am Heart J 2005; 149:820.
  48. Qunibi W, Moustafa M, Muenz LR, et al. A 1-year randomized trial of calcium acetate versus sevelamer on progression of coronary artery calcification in hemodialysis patients with comparable lipid control: the Calcium Acetate Renagel Evaluation-2 (CARE-2) study. Am J Kidney Dis 2008; 51:952.
  49. Di Iorio B, Bellasi A, Russo D, INDEPENDENT Study Investigators. Mortality in kidney disease patients treated with phosphate binders: a randomized study. Clin J Am Soc Nephrol 2012; 7:487.
  50. Wada K, Wada Y. Evaluation of aortic calcification with lanthanum carbonate vs. calcium-based phosphate binders in maintenance hemodialysis patients with type 2 diabetes mellitus: an open-label randomized controlled trial. Ther Apher Dial 2014; 18:353.
  51. Block GA, Wheeler DC, Persky MS, et al. Effects of phosphate binders in moderate CKD. J Am Soc Nephrol 2012; 23:1407.
  52. Demer LL, Tintut Y. Inflammatory, metabolic, and genetic mechanisms of vascular calcification. Arterioscler Thromb Vasc Biol 2014; 34:715.
  53. Mazière C, Salle V, Gomila C, Mazière JC. Oxidized low density lipoprotein increases RANKL level in human vascular cells. Involvement of oxidative stress. Biochem Biophys Res Commun 2013; 440:295.
  54. Lamprea-Montealegre JA, McClelland RL, Astor BC, et al. Chronic kidney disease, plasma lipoproteins, and coronary artery calcium incidence: the Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol 2013; 33:652.
  55. Cetinkaya F, Baysal K, Koçak H, Gürses N. The incidence and significance of increased backscatter in myocardial ultrasonography of patients on hemodialysis. Nephron 1996; 73:191.
  56. Rostand SG, Sanders C, Kirk KA, et al. Myocardial calcification and cardiac dysfunction in chronic renal failure. Am J Med 1988; 85:651.
  57. Cesani F, Villanueva-Meyer J. Intense myocardial and lung uptake of 99m-Tc-pyrophosphate using single photon emission computed tomography in a patient with end-stage renal disease and secondary hyperparathyroidism. Int Urol Nephrol 1996; 28:569.
  58. Goldsmith D, MacGinley R, Smith A, Covic A. How important and how treatable is vascular stiffness as a cardiovascular risk factor in renal failure? Nephrol Dial Transplant 2002; 17:965.
  59. London GM, Marchais SJ, Guerin AP, et al. Arterial structure and function in end-stage renal disease. Nephrol Dial Transplant 2002; 17:1713.
  60. Haydar AA, Hujairi NM, Covic AA, et al. Coronary artery calcification is related to coronary atherosclerosis in chronic renal disease patients: a study comparing EBCT-generated coronary artery calcium scores and coronary angiography. Nephrol Dial Transplant 2004; 19:2307.
  61. National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003; 42:S1.
  62. Moe SM, O'Neill KD, Reslerova M, et al. Natural history of vascular calcification in dialysis and transplant patients. Nephrol Dial Transplant 2004; 19:2387.
  63. Oschatz E, Benesch T, Kodras K, et al. Changes of coronary calcification after kidney transplantation. Am J Kidney Dis 2006; 48:307.
  64. Schankel K, Robinson J, Bloom RD, et al. Determinants of coronary artery calcification progression in renal transplant recipients. Am J Transplant 2007; 7:2158.
  65. Rosenblum IY, Black HE, Ferrell JF. The effects of various diphosphonates on a rat model of cardiac calciphylaxis. Calcif Tissue Res 1977; 23:151.
  66. 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.
  67. Hashiba H, Aizawa S, Tamura K, et al. Inhibitory effects of etidronate on the progression of vascular calcification in hemodialysis patients. Ther Apher Dial 2004; 8:241.
  68. Fleckenstein-Grün G, Thimm F, Frey M, Matyas S. Progression and regression by verapamil of vitamin D3-induced calcific medial degeneration in coronary arteries of rats. J Cardiovasc Pharmacol 1995; 26:207.
  69. Bleyer AJ, Burkart J, Piazza M, et al. Changes in cardiovascular calcification after parathyroidectomy in patients with ESRD. Am J Kidney Dis 2005; 46:464.
  70. Covic A, Kanbay M, Voroneanu L, et al. Vascular calcification in chronic kidney disease. Clin Sci (Lond) 2010; 119:111.