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Elevated FGF 23 and phosphorus are associated with coronary calcification in hemodialysis patients

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Abstract

Increased mortality of adult chronic hemodialysis (HD) patients is associated with coronary calcifications (CC), increased serum phosphorus (P), use of calcium (Ca)-containing P-binders, and vitamin D deficiency. Serum concentration of fibroblast growth factor 23 (FGF 23) is markedly elevated in adults receiving dialysis and is independently associated with increased mortality. Although coronary calcifications have been described in pediatric and adult HD patients, no significant association between serum FGF 23 and CC has been reported. In our study, 5/16 patients had CC. Patients with CC were older, had longer dialysis vintage and higher serum P. Serum Ca, total PTH, elemental Ca intake, and calcitriol doses were not different for CC patients. Serum FGF 23 levels were markedly elevated in all patients (mean 4,024, range 874–8,253), but significantly higher in patients with CC (4,247 ± 10,35 vs 2,427 ± 11,92, p = 0.01) and positively correlated with Agatston calcification score (r = 0.69, p = 0.003) and serum P (r = 0.49, p = 0.05). Using multivariate analysis, serum FGF 23 and serum P remained the most significant factors associated with Agatston score. This study confirms the occurrence of CC in pediatric HD patients and is the first to show a significant association between CC and elevated serum FGF 23 in children.

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References

  1. Foley RN, Parfrey PS, Sarnak MJ (1998) Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 32:S112–S119

    Article  CAS  Google Scholar 

  2. Kopple JD (2005) The phenomenon of altered risk factor patterns or reverse epidemiology in persons with advanced chronic kidney failure. Am J Clin Nutr 81:1257–1266

    Article  CAS  Google Scholar 

  3. Block GA, Raggi P, Bellasi A, Kooienga L, Spiegel DM (2007) Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Kidney Int 71:438–441

    Article  CAS  Google Scholar 

  4. Block GA, Spiegel DM, Ehrlich J, Mehta R, Lindbergh J, Dreisbach A, Raggi P (2005) Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney Int 68:1815–1824

    Article  CAS  Google Scholar 

  5. Kuro-o M (2010) Overview of the FGF23-Klotho axis. Pediatr Nephrol 25:583–590

    Article  Google Scholar 

  6. Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Juppner H, Wolf M (2008) Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359:584–592

    Article  CAS  Google Scholar 

  7. Wesseling-Perry K, Pereira RC, Wang H, Elashoff RM, Sahney S, Gales B, Juppner H, Salusky IB (2009) Relationship between plasma fibroblast growth factor-23 concentration and bone mineralization in children with renal failure on peritoneal dialysis. J Clin Endocrinol Metab 94:511–517

    Article  CAS  Google Scholar 

  8. Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, Wang Y, Chung J, Emerick A, Greaser L, Elashoff RM, Salusky IB (2000) Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 342:1478–1483

    Article  CAS  Google Scholar 

  9. Oh J, Wunsch R, Turzer M, Bahner M, Raggi P, Querfeld U, Mehls O, Schaefer F (2002) Advanced coronary and carotid arteriopathy in young adults with childhood-onset chronic renal failure. Circulation 106:100–105

    Article  Google Scholar 

  10. Shroff RC, McNair R, Figg N, Skepper JN, Schurgers L, Gupta A, Hiorns M, Donald AE, Deanfield J, Rees L, Shanahan CM (2008) Dialysis accelerates medial vascular calcification in part by triggering smooth muscle cell apoptosis. Circulation 118:1748–1757

    Article  CAS  Google Scholar 

  11. Civilibal M, Caliskan S, Adaletli I, Oflaz H, Sever L, Candan C, Canpolat N, Kasapcopur O, Kuruoglu S, Arisoy N (2006) Coronary artery calcifications in children with end-stage renal disease. Pediatr Nephrol 21:1426–1433

    Article  Google Scholar 

  12. Srivaths PR, Silverstein DM, Leung J, Krishnamurthy R, Goldstein SL (2010) Malnutrition-inflammation-coronary calcification in pediatric patients receiving chronic hemodialysis. Hemodial Int 14:263–269

    Article  Google Scholar 

  13. Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R (1990) Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15:827–832

    Article  CAS  Google Scholar 

  14. Van Husen M, Fischer AK, Lehnhardt A, Klaassen I, Moller K, Muller-Wiefel DE, Kemper MJ (2010) Fibroblast growth factor 23 and bone metabolism in children with chronic kidney disease. Kidney Int 78:200–206

    Article  Google Scholar 

  15. Goldstein SL, Baronette S, Gambrell TV, Currier H, Brewer ED (2002) nPCR assessment and IDPN treatment of malnutrition in pediatric hemodialysis patients. Pediatr Nephrol 17:531–534

    Article  Google Scholar 

  16. Juarez-Congelosi M, Orellana P, Goldstein SL (2007) Normalized protein catabolic rate versus serum albumin as a nutrition status marker in pediatric patients receiving hemodialysis. J Ren Nutr 17:269–274

    Article  Google Scholar 

  17. Razzaque MS (2009) The FGF23-Klotho axis: endocrine regulation of phosphate homeostasis. Nat Rev Endocrinol 5:611–619

    Article  CAS  Google Scholar 

  18. Isakova T, Gutierrez OM, Chang Y, Shah A, Tamez H, Smith K, Thadhani R, Wolf M (2009) Phosphorus binders and survival on hemodialysis. J Am Soc Nephrol 20:388–396

    Article  CAS  Google Scholar 

  19. Jean G, Bresson E, Terrat JC, Vanel T, Hurot JM, Lorriaux C, Mayor B, Chazot C (2009) Peripheral vascular calcification in long-haemodialysis patients: associated factors and survival consequences. Nephrol Dial Transplant 24:948–955

    Article  CAS  Google Scholar 

  20. Balci M, Kirkpantur A, Gulbay M, Gurbuz OA (2010) Plasma fibroblast growth factor-23 levels are independently associated with carotid artery atherosclerosis in maintenance hemodialysis patients. Hemodial Int 14:425–432

    Article  Google Scholar 

  21. Gutierrez OM, Januzzi JL, Isakova T, Laliberte K, Smith K, Collerone G, Sarwar A, Hoffmann U, Coglianese E, Christenson R, Wang TJ, deFilippi C, Wolf M (2009) Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 119:2545–2552

    Article  CAS  Google Scholar 

  22. Mirza MA, Larsson A, Melhus H, Lind L, Larsson TE (2009) Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population. Atherosclerosis 207:546–551

    Article  CAS  Google Scholar 

  23. Hu MC, Shi M, Zhang J, Quinones H, Griffith C, Kuro OM, Moe OW (2011) Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol 22:124–136

    Article  CAS  Google Scholar 

  24. El-Abbadi MM, Pai AS, Leaf EM, Yang HY, Bartley BA, Quan KK, Ingalls CM, Liao HW, Giachelli CM (2009) Phosphate feeding induces arterial medial calcification in uremic mice: role of serum phosphorus, fibroblast growth factor-23, and osteopontin. Kidney Int 75:1297–1307

    Article  CAS  Google Scholar 

  25. Bacchetta J, Dubourg L, Harambat J, Ranchin B, Abou-Jaoude P, Arnaud S, Carlier MC, Richard M, Cochat P (2010) The influence of glomerular filtration rate and age on fibroblast growth factor 23 serum levels in pediatric chronic kidney disease. J Clin Endocrinol Metab 95:1741–1748

    Article  CAS  Google Scholar 

  26. Teng M, Wolf M, Ofsthun MN, Lazarus JM, Hernan MA, Camargo CA Jr, Thadhani R (2005) Activated injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol 16:1115–1125

    Article  CAS  Google Scholar 

  27. USRDS (2009) Annual data report: atlas of end-stage renal disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD

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Correspondence to Poyyapakkam R. Srivaths.

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Srivaths, P.R., Goldstein, S.L., Silverstein, D.M. et al. Elevated FGF 23 and phosphorus are associated with coronary calcification in hemodialysis patients. Pediatr Nephrol 26, 945–951 (2011). https://doi.org/10.1007/s00467-011-1822-0

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  • DOI: https://doi.org/10.1007/s00467-011-1822-0

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