Clinical and Experimental Nephrology

, Volume 17, Issue 3, pp 416–423 | Cite as

The effects of iron on FGF23-mediated Ca–P metabolism in CKD patients

  • Serpil Muge Deger
  • Yasemin Erten
  • Ozge Tugce Pasaoglu
  • Ulver Boztepe Derici
  • Kadriye Altok Reis
  • Kursad Onec
  • Hatice Pasaoglu
Original Article

Abstract

Background

Fibroblast growth factor 23 (FGF23) is an important counterregulatory hormone for phosphate homeostasis. Since it has been reported that iron administration induces hypophosphatemic osteomalacia by triggering FGF23 synthesis, we hypothesized that iron administration might lead to a further increase in FGF23, resulting in alterations to Ca–P metabolism in a stage 5 CKD population.

Methods

This cross-sectional study was performed in a single center, and involved 73 hemodialysis patients (47.7 ± 15.74 years old, 68.5 % men), 29 peritoneal dialysis patients (44.55 ± 15.05 years old, 62.1 % men), and 55 healthy (43.57 ± 14.36 years old, 55.6 % men) subjects. The dialysis group was subcategorized according to iron therapy administration into users and nonusers.

Results

The median iFGF23 level was significantly higher in the dialysis population than in the healthy controls [88.050 (25.2–1038.3) pg/ml versus 46.95 (2.4–356) pg/ml (p < 0.001)]. In the dialysis population, a significantly lower median iFGF23 level was observed in iron therapy users than in nonusers [87.6 (25.2–1038.3) versus 119 (51.6–1031); respectively, p = 0.045]. A significant negative association between iron administration and iFGF23 level was revealed by both univariate (r = −0.237, p = 0.016) and multivariate (β = −0.221, p = 0.032) analysis. No association was found between iFGF23 and serum ferritin and iron levels. Also, there was no association between iron therapy and serum phosphate level.

Conclusion

In contrast to what is seen for the general population, this study showed that there was a negative relationship between iron administration and serum iFGF23 level in a dialysis population. We can therefore conclude that if high levels of FGF23 are harmful, iron therapy may have a beneficial effect on bone metabolism by reducing FGF23 levels in a dialysis population.

Keywords

FGF23 Dialysis Iron therapy Mineral metabolism 

References

  1. 1.
    Saito T, Fukumoto S. Fibroblast growth factor 23 (FGF23) and disorders of phosphate metabolism. Int J Pediatr Endocrinol. 2009;2009:496514.PubMedCrossRefGoogle Scholar
  2. 2.
    Samadfam R, Richard C, Nguyen-Yamamoto L, Bolivar I, Goltzman D. Bone formation regulates circulating concentrations of fibroblast growth factor 23. Endocrinology. 2009;150:4835–45.PubMedCrossRefGoogle Scholar
  3. 3.
    Krajisnik T, Bjorklund P, Marsell R, Ljunggren O, Akerstrom G, Jonsson KB, Westin G, Larsson TE. Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells. J Endocrinol. 2007;195:125–31.PubMedCrossRefGoogle Scholar
  4. 4.
    Razzaque MS, Lanske B. The emerging role of the fibroblast growth factor-23-klotho axis in renal regulation of phosphate homeostasis. J Endocrinol. 2007;194:1–10.PubMedCrossRefGoogle Scholar
  5. 5.
    Yamashita T, Yoshioka M, Itoh N. Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain. Biochem Biophys Res Commun. 2000;277:494–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Juppner H, Wolf M. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008;359:584–92.PubMedCrossRefGoogle Scholar
  7. 7.
    Wolf M. Fibroblast growth factor 23 and the future of phosphorus management. Curr Opin Nephrol Hypertens. 2009;18:463–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Filler G, Liu D, Huang SH, Casier S, Chau LA, Madrenas J. Impaired GFR is the most important determinant for FGF-23 increase in chronic kidney disease. Clin Biochem. 2011;44:435–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Isakova T, Wolf MS. FGF23 or PTH: which comes first in CKD ? Kidney Int. 2010;78:947–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Hasegawa H, Nagano N, Urakawa I, Yamazaki Y, Iijima K, Fujita T, Yamashita T, Fukumoto S, Shimada T. Direct evidence for a causative role of FGF23 in the abnormal renal phosphate handling and vitamin D metabolism in rats with early-stage chronic kidney disease. Kidney Int. 2010;78:975–80.PubMedCrossRefGoogle Scholar
  11. 11.
    Sato K, Nohtomi K, Demura H, Takeuchi A, Kobayashi T, Kazama J, Ozawa H. Saccharated ferric oxide (SFO)-induced osteomalacia: in vitro inhibition by SFO of bone formation and 1,25-dihydroxy-vitamin D production in renal tubules. Bone. 1997;21:57–64.PubMedCrossRefGoogle Scholar
  12. 12.
    Schouten BJ, Hunt PJ, Livesey JH, Frampton CM, Soule SG. FGF23 elevation and hypophosphatemia after intravenous iron polymaltose: a prospective study. J Clin Endocrinol Metab. 2009;94:2332–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Schouten BJ, Doogue MP, Soule SG, Hunt PJ. Iron polymaltose-induced FGF23 elevation complicated by hypophosphataemic osteomalacia. Ann Clin Biochem. 2009;46:167–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Shimizu Y, Tada Y, Yamauchi M, Okamoto T, Suzuki H, Ito N, Fukumoto S, Sugimoto T, Fujita T. Hypophosphatemia induced by intravenous administration of saccharated ferric oxide: another form of FGF23-related hypophosphatemia. Bone. 2009;45:814–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Dhingra R, Sullivan LM, Fox CS, Wang TJ, D’Agostino RB Sr, Gaziano JM, Vasan RS. Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. Arch Intern Med. 2007;167:879–85.PubMedCrossRefGoogle Scholar
  16. 16.
    Fliser D, Kollerits B, Neyer U, Ankerst DP, Lhotta K, Lingenhel A, Ritz E, Kronenberg F, Kuen E, Konig P, Kraatz G, Mann JF, Muller GA, Kohler H, Riegler P. Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. J Am Soc Nephrol. 2007;18:2600–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Okada M, Imamura K, Iida M, Fuchigami T, Omae T. Hypophosphatemia induced by intravenous administration of saccharated iron oxide. Klin Wochenschr. 1983;61:99–102.PubMedCrossRefGoogle Scholar
  18. 18.
    Sato K, Shiraki M. Saccharated ferric oxide-induced osteomalacia in Japan: iron-induced osteopathy due to nephropathy. Endocr J. 1998;45:431–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Takeda Y, Komaba H, Goto S, Fujii H, Umezu M, Hasegawa H, Fujimori A, Nishioka M, Nishi S, Fukagawa M. Effect of intravenous saccharated ferric oxide on serum FGF23 and mineral metabolism in hemodialysis patients. Am J Nephrol. 2011;33:421–6.PubMedCrossRefGoogle Scholar
  20. 20.
    Yamasaki K, Hagiwara H. Excess iron inhibits osteoblast metabolism. Toxicol Lett. 2009;191:211–5.PubMedCrossRefGoogle Scholar
  21. 21.
    Seiler S, Heine GH, Fliser D. Clinical relevance of FGF-23 in chronic kidney disease. Kidney Int Suppl 2009;114:S34–S42.Google Scholar

Copyright information

© Japanese Society of Nephrology 2012

Authors and Affiliations

  • Serpil Muge Deger
    • 1
    • 3
  • Yasemin Erten
    • 1
  • Ozge Tugce Pasaoglu
    • 2
  • Ulver Boztepe Derici
    • 1
  • Kadriye Altok Reis
    • 1
  • Kursad Onec
    • 1
  • Hatice Pasaoglu
    • 2
  1. 1.Department of Internal Medicine, Department of NephrologyGazi University Faculty of MedicineBesevler, AnkaraTurkey
  2. 2.Department of BiochemistryGazi University Faculty of MedicineBesevler, AnkaraTurkey
  3. 3.Division of NephrologyVanderbilt University Medical CenterNashvilleUSA

Personalised recommendations