Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 4, April, p. 499–505

doi: 10.17219/acem/82517

Publication type: original article

Language: English

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The importance of fetuin-A in vascular calcification in children with chronic kidney disease

Irena Makulska1,A,B,C,D, Maria Szczepańska2,B,D, Dorota Drożdż3,B, Dorota Polak-Jonkisz1,B, Danuta Zwolińska1,A,C,D,E,F

1 Department of Pediatric Nephrology, Faculty of Medicine, Wroclaw Medical University, Poland

2 Department of Pediatrics in Zabrze, Medical University of Silesia, Katowice, Poland

3 Dialysis Unit, Jagiellonian University Medical College, Kraków, Poland


Background. The status of the cardiovascular (CV) system in children with chronic kidney disease (CKD) is significantly influenced by increasing stiffness of the arterial wall. This largely depends on the shortage of local and systemic inhibitors of soft tissue calcification.
Objectives. The aim of the study was to evaluate the role of fetuin-A in conjunction with other factors in the progressive hardening of the vascular wall in these children. We examined serum fetuin-A concentrations in relation to renal function, dialysis modality, and other clinical and biochemical markers promoting vascular calcification.
Material and Methods. Twenty children on peritoneal dialysis (PD), 20 on hemodialysis (HD), 36 treated conservatively, and 26 healthy subjects were enrolled into a cross-sectional study. In all children, fetuin-A and numerous clinical and biochemical parameters were measured.
Results. The fetuin-A concentration was significantly lower in children on hemodialysis (HD) vs children on peritoneal dialysis (PD), conservatively treated subjects, and the control group. In sick children, fetuinA concentration negatively correlated with dialysis vintage, PWV/ht, phosphate concentration, calcium phosphate product (CaxP), cumulative doses of calcium, and vitamin D3. In the whole study population, fetuin-A negatively correlated with blood pressure (BP), pulse wave velocity indexed to height (PWV/ht), intact parathyroid hormone (iPTH), high sensitivity C-reactive protein (hsCRP), and cholesterol concentrations.
Conclusion. In children with CKD, the decreased concentration of fetuin-A is related to other vascular calcification risk factors. Serum fetuin-A concentration may play a role in the identification of vascular disease risk factors in this population.

Key words

children, chronic kidney disease, fetuin-A

References (40)

  1. London GM, Marchais SJ, Guerin AP, Metivier F, Adda H. Arterial structure and function in end-stage renal disease. Nephrol Dial Transplant. 2002;17(10):1713–1724.
  2. London GM, Marchais SJ, Guerin AP. Arterial stiffness and function in end-stage renal disease. Adv Kidney Dis. 2004;11(2):202–209.
  3. Quinibi WY. Reducing the burden of cardiovascular calcification in patients with chronic kidney disease. J Am Soc Nephrol. 2005;16(Suppl 2):S95–S102.
  4. 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(20):1478–1483.
  5. 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(1):100–110.
  6. 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(8):2208–2218.
  7. Deriki U, El Nahas M. Vascular calcifications in uremia: Old concept and new insights. Semin Dial. 2006;19(1):60–68.
  8. Floege J, Ketteler M. Vascular calcification in patients with end-stage renal disease. Nephrol Dial Transplant. 2004;19(Suppl 5):V59–66.
  9. Schaeffer C, Heiss C, Schwarz A, et al. The serum protein α2-Here-mans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification. J Clin Invest. 2003;112(3):357–366.
  10. Price PA, Thomas GR, Bardini AW, Figueira WF, Caputo JM, Williamson MK. Discovery of a high molecular weight complex of calcium, phosphate, fetuin and matrix gamma-carboxyglutamic acid protein in the serum of etidronate-treated rats. J Biol Chem. 2002;277(6):3926–3934.
  11. Heiss A, DuChesne A, Denecke B, et al. Structural basis of calcification inhibition by α2-HS glycoprotein/fetuin-A. Formation of colloidal calciprotein particles. J Biol Chem. 2003;278(15):13333–13341.
  12. Chen NX, O’Neill KD, Chen X, et al. Fetuin-A uptake in bovine vascular smooth muscle cells is calcium dependent and mediated by annexins. Am J Renal Physiol. 2007;292(2):F599–606.
  13. Reynolds JL, Skepper JN, McNair, et al. Multifactorial roles for serum protein fetuin-A in inhibition of human vascular smooth muscle cell calcification. J Am Soc Nephrol. 2005;16(10):2920–2930.
  14. Schaible J, Wigger M, Staude H, et al. Serum fetuin-A and vitamin D in children with mild-to-severe chronic kidney disease: A cross-sectional study. Nephrol Dial Transplant. 2012;27(3):1107–1113.
  15. Scialla JJ, Kao WH, Crainiceanu C, et al. Biomarkers of vascular calcification and mortality in patients with ESRD. Clin J Am Soc Nephrol. 2014;9(4):745–755.
  16. Ketteler M, Bongartz P, Westenfeld R, et al. Association of low fetuin-A levels (AHSG) concentrations in serum in patients on dialysis with cardiovascular mortality: A cross sectional study. Lancet. 2003;361(9360):827–833.
  17. 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.
  18. Sheth RD, Perez MD, Goldstein SL. Cardiovascular calcifications in pediatric patients receiving maintenance dialysis. Pediatr Nephrol. 2003;18(8):810–813.
  19. Civilibal M, Caliskan S, Adaletli I, et al. Coronary artery calcifications in children with end-stage renal disease. Pediatr Nephrol. 2006;21(10):1426–1433.
  20. Bakiler AR, Yavascan O, Harputluoglu N, Kara OD, Aksu N. Evaluation of aortic stiffness in children with chronic renal failure. Pediatr Nephrol. 2007;22(11):1911–1919.
  21. Collura G, Capozza N, Francalanci P, et al. Arterial changes in children undergoing renal transplantation. Trans Proceed. 2008;40:1891–1894.
  22. Schwartz GJ, Gauthier B. A simple estimate of glomerular filtration rate in adolescent boys. J Pediatr. 1985:106(3):522–526.
  23. The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents; U.S. Department of Health and Human Services; National Institutes of Health, National Heart, Lung, and Blood Institute NIH Publication No. 05-5267. 2005.
  24. Mavroudis C, Backer CL. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children. Pediatr Cardiac Surg. 2008;251.
  25. Makulska I, Szczepańska M, Drożdż D, Polak-Jonkisz D, Zwolińska D. Skin autofluorescence as a marker of cardiovascular risk in children with chronic kidney disease. Pediatr Nephrol. 2013;28(1):121–128.
  26. Coen G, Manni M, Agnoli A, et al. Cardiac calcifications: Fetuin-A and other risk factors in hemodialysis patients. ASAIO J. 2006;52(2):150–156.
  27. Porazko T, Kuźniar J, Kusztal M, et al. Increased aortic wall stiffness associated with low circulating fetuin-A and high C-reactive protein in predialysis patients. Nephron Clin Pract. 2009;113(2):81–87.
  28. Dervisoglu E, Kir HM, Kalender B, Caglayan CO, Eraldemir CO. Serum fetuin-A concentrations are inversely related to cytokines concentrations in patients with chronic renal failure. Cytokine. 2008;44(3):323–327.
  29. Shroff RC, Shah V, Hiorns MP, et al. The circulation calcification inhibitors, fetuin-A and osteoprotegerin but not Matrix Gla protein are associated with vascular stiffness and calcification in children on dialysis. Nephrol Dial Transplant. 2008;23(10):3263–3271.
  30. Ziółkowska H, Brzeski M, Roszkowska-Blaim M. Determinants of the intima media thickness in children and adolescents with chronic kidney disease. Pediatr Nephrol. 2008;23(5):805–811.
  31. Hermans MM, Brandenburg V, Ketteler M, et al. Study on the relationship of serum fetuin-A concentration with aortic stiffness in patients on dialysis. Nephrol Dial Transplant. 2006;21(5):1293–1299.
  32. van Summeren MJ, Hameleers JM, Schurgers LJ, et al. Circulating calcification inhibitors and vascular properties in children after renal transplantation. Pediatr Nephrol. 2008;23(6):985–993.
  33. Jahnen-Dechent W, Schinke T, Trindl A, et al. Cloning and targeted deletion of the mouse fetuin gene. J Biol Chem. 1997;272(50):31496–31503.
  34. Eraso LH, Ginwala N, Qasim AN, et al. Association of lower plasma fetuin-A levels with peripheral arterial disease in type-2 diabetes. Diabetes Care. 2010;33(2):408–410.
  35. Westenfeld R, Schäfer C, Krüger T, et al. Fetuin-A protects against atherosclerotic calcification in CKD. J Am Soc Nephrol. 2009;20(6):1264–1274.
  36. Kirkpantur A, Altun B, Hazirolan T, et al. Association among serum fetuin-A level, coronary artery calcification and bone mineral densitometry in maintenance of hemodialysis patients. Artif Organs. 2009; 33(10):844–854.
  37. Moe SM, Reslerova M, Ketteler M, et al. Role of calcification inhibitors in the pathogenesis of vascular calcification in chronic kidney disease (CKD). Kidney Int. 2005;67(6):2295–2304.
  38. Caglar K, Yilmaz MI, Saglam M, et al. Serum fetuin-A concentration and endothelial dysfunction in chronic kidney disease. Nephron Clin Pract. 2008;108(3):233–420.
  39. Toussaint ND, Lau KK, Strauss BJ, Polkinghorne KR, Kerr PG. Associations between vascular calcification, arterial stiffness and bone mineral density in chronic kidney disease. Nephrol Dial Transplant. 2008;23(2):586–593.
  40. Ford ML, Tomlinson LA, Smith ER, Rajkumar C, Holt SG. Fetuin-A is an independent determinant of change of aortic stiffness over 1 year in non-diabetic patients with CKD stage 3 and 4. Nephrol Dial Transplant. 2010;25(6):1853–1858.