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Vol. 27, No. 1, 2007
Issue release date: March 2007
Am J Nephrol 2007;27:75–83

Serum Levels of Calcification Inhibition Proteins and Coronary Artery Calcium Score: Comparison between Transplantation and Dialysis

Mazzaferro S. · Pasquali M. · Pugliese F. · Barresi G. · Carbone I. · Francone M. · Sardella D. · Taggi F.
aDivision of Nephrology, Department of Clinical Science, bDepartment of Radiological Science, University of Rome ‘La Sapienza’, and cDepartment of Environment and Primary Prevention of the Istituto Superiore di Sanità, Rome, Italy

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Vascular calcifications in CKD are now linked to serum alterations of both divalent ions and calcification inhibitory proteins. Due to possible biochemical differences between dialysis (D) and transplantation (Tx), we examined the entity and severity of these biochemical modifications and of coronary artery calcium score separately in these two populations. We assayed, besides standard markers of inflammation, divalent ions and serum levels of fetuin, matrix Gla protein (MGP) and osteoprotegerin (OPG), in 51 Tx patients (age 45 ± 12 years; 30 males, 21 females; previous D duration 4.8 ± 4.2 years; Tx since 6.6 ± 5.5 years; Cr 1.8 ± 0.6 mg/dl) and in 49 D patients (age 49 ± 14 years; 30 males,19 females; D duration 5.6 ± 4.8 years). Additionally, coronary calcium score (AS) was evaluated by cardiac multi-slice CT. Compared with D patients, Tx patients had better values of divalent ions and inflammation markers, and lower prevalence (65 vs. 86%; p < 0.02) and severity (AS = 570 ± 1,637 vs. 1,311 ± 3,128; p < 0.008) of coronary calcification. In addition, a tendency toward normalization for all of the three calcification inhibitory proteins was evident. In both Tx and D, AS correlated with age and OPG (Tx: rs = 0.439, p < 0.001, and rs = 0.510, p < 0.0001; D: rs = 0.471, p < 0.001, and rs = 0.403, p < 0.005, respectively); in D patients, a correlation was present also with D duration (rs = 0.435; p < 0.002), other markers of inflammation and, notably, fetuin (rs = –0.442; p < 0.002). Regression analysis selected previous time on D in Tx patients (rm = 0.400; p < 0.004), and C-reactive protein and OPG in D patients (rm = 0.518; p < 0.004) as the most predictive parameters of AS. Discriminant analysis confirmed the major role of age and D duration in the appearance of AS and evidenced male gender as a distinct risk condition. At variance, Tx duration was never associated with AS. In conclusion, as compared to D, renal Tx patients show serum levels of calcification inhibition proteins and of divalent ions closer to normal. As this is associated with a lower prevalence and severity of AS, it is suggested that Tx antagonize the accelerating role of D in the progression of vascular calcification. Assessment of both coronary calcifications and serum levels of calcification inhibitory proteins may be of value to identify those subjects at higher risk of development and progression of vascular lesions, among whom males have the highest rate.

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  1. Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM: Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 2004;15:2208–2218.
  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. Foley RN, Parfrey PS, Sarnak MJ: Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998;32(suppl 3):S112–S119.

    External Resources

  4. Jono S, McKee MD, Murry CE, Shioi A, Nishizawa Y, Mori K, Morii H, Giachelli CM: Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 2000;87:E10–E17.
  5. Reynolds JL, Joannides AJ, Skepper JN, McNair R, Schurgers LJ, Proudfoot D, Jahnen-Dechent W, Weissberg PL, Shanahan CM: 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.
  6. Yang H, Curinga G, Giachelli CM: Elevated extracellular calcium levels induce smooth muscle cell matrix mineralization in vitro. Kidney Int 2004;66:2293–2299.
  7. Henley C, Colloton M, Cattley RC, Shatzen E, Towler DA, Lacey D, Martin D: 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.
  8. Giachelli CM: Vascular calcification mechanisms. J Am Soc Nephrol 2004;15:2959–2964.
  9. Ketteler M, Gross ML, Ritz E: Calcification and cardiovascular problems in renal failure. Kidney Int 2005;67(suppl 94):S120–S127.

    External Resources

  10. Yuen D, Pierratos A, Richardson RMA, Chan CT: The natural history of coronary calcification progression in a cohort of nocturnal hemodialysis patients. Nephrol Dial Transplant 2006;21:1407–1412.
  11. 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.
  12. Block GA, Spiegel DM, Ehrlich J, Mehta R, Lindbergh J, Dreisbach A, Raggi P: Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney Int 2005;68:1815–1824.
  13. Moe SM, Reslerova M, Ketteler M, O’Neill K, Duan D, Koczman J, Westenfeld R, Jahnen-Dechent W, Chen NX: Role of calcification inhibitors in the pathogenesis of vascular calcification in chronic kidney disease (CKD). Kidney Int 2005;67:2295–2304.
  14. Hernandez D, Rufino M, Bartolomei S, Gonzalez-Rinne A, Lorenzo V, Cobo M, Torres A: Clinical impact of preexisting vascular calcifications on mortality after renal transplantation. Kidney Int 2005;67:2015–2020.
  15. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R: Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 1990;15:827–832.
  16. Rumberger JA, Brundage BH, Rader DJ, Kondos G: Electron beam computed tomographic coronary calcium scanning: a review and guidelines for use in asymptomatic persons. Mayo Clin Proc 1999;74:243–252.
  17. Kestenbaum B, Sampson JN, Rudser KD, Patterson DJ, Seliger SL, Young B, Sherrard DJ, Andress DL: Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol 2005;16:520–528.
  18. Tonelli M, Sacks F, Pfeffer M, Gao Z, Curhan G; Cholesterol and recurrent events trial investigators: relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation 2005;112:2627–2633.
  19. 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.
  20. Moe SM, O’Neill KD, Reslerova M, Fineberg N, Persohn S, Meyer CA: Natural history of vascular calcification in dialysis and transplant patients. Nephrol Dial Transplant 2004;19:2387–2393.
  21. Oschatz E, Benesch T, Kodras K, Hoffman U, Haas M: Changes of coronary calcification after kidney transplantation Am J Kidney Dis 2006;48:307–313.
  22. Schinke T, Amendt C, Trindl A, Poschke O, Muller-Esterl W, Jahnen-Dechent W: The serum protein alpha2-HS glycoprotein/fetuin inhibits apatite formation in vitro and in mineralizing calvaria cells. A possible role in mineralization and calcium homeostasis. J Biol Chem 1996;271:20789–20796.
  23. Schafer C, Heiss A, Schwarz A, Westenfeld R, Ketteler M, Floege J, Muller-Esterl W, Schinke T, Jahnen-Dechent W: 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.
  24. Ketteler M, Bongartz P, Westenfeld R, Wildberger JE, Mahnken AH, Bohm R, Metzger T, Wanner C, Jahnen-Dechent W, Floege J: Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study. Lancet 2003;361:827–833.
  25. Vermeer C: Gamma-carboxyglutamate-containing proteins and the vitamin K-dependent carboxylase. Biochem J 1990;266:625–636.
  26. Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G: Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 1997;386:78–81.
  27. Jono S, Ikari Y, Vermeer C, Dissel P, Hasegawa K, Shioi A, Taniwaki H, Kizu A, Nishizawa Y, Saito S: Matrix Gla protein is associated with coronary artery calcification as assessed by electron-beam computed tomography. Thromb Haemost 2004;91:790–794.
  28. Schurgers LJ, Teunissen KJ, Knapen MH, Geusens P, van der Heijde D, Kwaijtaal M, van Diest R, Ketteler M, Vermeer C: Characteristics and performance of an immunosorbent assay for human matrix Gla-protein. Clin Chim Acta 2005;351:131–138.
  29. Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ, Simonet WS: Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 1998;12:1260–1268.
  30. Schoppet M, Al-Fakhri N, Franke FE, Katz N, Barth PJ, Maisch B, Preissner KT, Hofbauer LC: 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;89:4104–4112.
  31. Jono S, Ikari Y, Shioi A, Mori K, Miki T, Hara K, Nishizawa Y: Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation 2002;106:1192–1194.
  32. Kiechl S, Schett G, Wenning G, Redlich K, Oberhollenzer M, Mayr A, Santer P, Smolen J, Poewe W, Willeit J: Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation 2004;109:2175–2180.
  33. Morena M, Terrier N, Jaussent I, Leray-Moragues H, Chalabi L, Rivory JP, Maurice F, Delcourt C, Cristol JP, Canaud B, Dupuy AM: Plasma osteoprotegerin is associated with mortality in hemodialysis patients. J Am Soc Nephrol 2006;17:262–270.
  34. Hjelmesaeth J, Ueland T, Flyvbjerg A, Bollerslev J, Leivestad T, Jenssen T, Hansen TK, Thiel S, Sagedal S, Roislien J, Hartmann A: Early posttransplant serum osteoprotegerin levels predict long-term (8 year) patient survival and cardiovascular death in renal transplant patients. J Am Soc Nephrol 2006;17:1746–1754.
  35. Kazama JJ, Shigematsu T, Yano K, Tsuda E, Miura M, Iwasaki Y, Kawaguchi Y, Gejyo F, Kurokawa K, Fukagawa M: Increased circulating levels of osteoclastogenesis inhibitory factor (osteoprotegerin) in patients with chronic renal failure. Am J Kidney Dis 2002;39:525–532.
  36. Kudlacek S, Schneider B, Woloszczuk W, Pietschmann P, Willvonseder R: Serum levels of osteoprotegerin increase with age in a healthy adult population. Bone 2003;32:681–686.
  37. Coen G, Ballanti P, Balducci A, Calabria S, Fischer MS, Jankovic L, Manni M, Morosetti M, Moscaritolo E, Sardella D, Bonucci E: Serum osteoprotegerin and renal osteodystrophy. Nephrol Dial Transplant 2002;17:233–238.
  38. Haas M, Leko-Mohr Z, Roschger P, Kletzmayr J, Schwarz C, Domenig C, Zsontsich T, Klaushofer K, Delling G, Oberbauer R: Osteoprotegerin and parathyroid hormone as markers of high-turnover osteodystrophy and decreased bone mineralization in hemodialysis patients. Am J Kidney Dis 2002;39:580–586.
  39. Szulc P, Hofbauer LC, Huefelder AE, Roth S, Delmas PD: Osteoprotegerin serum levels in men: correlation with age, estrogen, and testosterone status. J Clin Endocrinol Metab 2001;86:3162–3165.
  40. Nitta K, Akiba T, Uchida K, Kawashima A, Yumura W, Kabaya T, Nihei H: The progression of vascular calcification and serum osteoprotegerin levels in patients on long-term hemodialysis. Am J Kidney Dis 2003;42:303–309.
  41. Schoppet M, Sattler AM, Schaefer JR, Herzum M, Maisch B, Hofbauer LC: Increased osteoprotegerin serum levels in men with coronary artery disease. J Clin Endocrinol Metab 2003;88:1024–1028.
  42. Browner WS, Lui LY, Cummings SR: Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women. J Clin Endocrinol Metab 2001;86:631–637.
  43. Allison MA, Wright CM: Age and gender are the strongest clinical correlates of prevalent coronary calcification. Int J Cardiol 2005;98:325–330.
  44. Shisen J, Leung DY, Juergens CP: Gender and age differences in the prevalence of coronary artery calcification in 953 Chinese subjects. Hearth Lung Circ 2005;14:69–73.

    External Resources

  45. Coen G, Manni M, Agnoli A, Balducci A, Dessi M, De Angelis S, Jankovic L, Mantella D, Morosetti M, Naticchia A, Nofroni I, Romagnoli A, Gallucci MT, Tomassini M, Simonetti G, Splendiani G: Cardiac calcifications: fetuin-A and other risk factors in hemodialysis patients. ASAIO J 2006;52:150–156.

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