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Vol. 33, No. 5, 2011
Issue release date: May 2011
Am J Nephrol 2011;33:421–426
(DOI:10.1159/000327019)

Effect of Intravenous Saccharated Ferric Oxide on Serum FGF23 and Mineral Metabolism in Hemodialysis Patients

Takeda Y. · Komaba H. · Goto S. · Fujii H. · Umezu M. · Hasegawa H. · Fujimori A. · Nishioka M. · Nishi S. · Fukagawa M.
aDivision of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, Kobe, bDivision of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara, cDepartment of Nephrology and Blood Purification Center, Rokko Island Hospital, dDivision of Blood Purification and Kidney Center, Konan Hospital, and eSumiyoshigawa Clinic, Kobe, Japan

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Abstract

Background/Aims: Fibroblast growth factor-23 (FGF23) plays a central role in the development of hypophosphatemia and inappropriately low 1,25-dihydroxyvitamin D induced by iron therapy for iron-deficiency anemia. The aim of this study was to examine the effect of intravenous saccharated ferric oxide on serum FGF23 levels and mineral metabolism in hemodialysis patients. Methods: This prospective study enrolled 27 hemodialysis patients who had iron-deficiency anemia defined by a hemoglobin concentration <10.5 g/dl and serum ferritin <100 ng/ml. Intravenous saccharated ferric oxide at a dose of 40 mg was administered three times weekly over 3 weeks. The dose of active vitamin D and phosphate binders was kept unchanged. Serum FGF23, intact parathyroid hormone (PTH) and other parameters were prospectively monitored for 5 weeks. Results: Serum FGF23 levels were markedly elevated [3,453 (338–6,383) pg/ml] at baseline. After 3 weeks of intravenous saccharated ferric oxide treatment, serum FGF23 further increased to 4,701 (1,251–14,396) pg/ml, and returned to the baseline values after 2 weeks of observation. There was also a significant decrease in intact PTH but no changes in serum calcium and phosphorus. Conclusions: Intravenous saccharated ferric oxide induces further increase in elevated FGF23 levels in hemodialysis patients. This increase does not induce hypophosphatemia and inappropriately low 1,25-dihydroxyvitamin D in the absence of functioning kidney, but may result in transient PTH suppression – possibly by directly acting on the parathyroid.



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References

  1. Quarles LD: Endocrine functions of bone in mineral metabolism regulation. J Clin Invest 2008;118:3820–3828.
  2. Saito H, Kusano K, Kinosaki M, et al: Human fibroblast growth factor-23 mutants suppress Na-dependent phosphate cotransport activity and 1α,25-dihydroxyvitamin D3 production. J Biol Chem 2003;278:2206–2211.
  3. Shimada T, Hasegawa H, Yamazaki Y, et al: FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 2004;19:429–435.
  4. Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V, et al: The parathyroid is a target organ for FGF23 in rats. J Clin Invest 2007;117:4003–4008.
  5. Krajisnik T, Bjorklund P, Masell R, et al: Fibroblast growth factor-23 regulates parathyroid hormone and 1α-hydroxylase expression in cultured bovine parathyroid cells. J Endocrinol 2007;195:125–131.
  6. ADHR Consortium: Autosomal dominant hypophosphataemic rickets is associated with mutations in FGF23. Nat Genet 2000;26:345–348.
  7. Yamazaki Y, Okazaki R, Shibata M, et al: increased circulatory level of biologically active full-length FGF23 in patients with hypophosphatemic rickets/osteomalacia. J Clin Endocrinol Metab 2002;87:4957–4960.
  8. Jonsson KB, Zahradnik R, Larsson T, et al: Fibroblast growth factor-23 in oncogenic osteomalacia and X-linked hypophosphatemia. N Engl J Med 2003;348:1656–1663.
  9. Shimada T, Mizutani S, Muto T, et al: Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci USA 2001;98:6500–6505.
  10. Kurosu H, Ogawa Y, Miyoshi M, et al: Regulation of fibroblast growth factor-23 signaling by Klotho. J Biol Chem 2006;281:6120–6123.
  11. Urakawa I, Yamazaki Y, Shimada T, et al: Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 2006;444:770–774.
  12. Komaba H, Fukagawa M: FGF23-parathyroid interaction: implications in chronic kidney disease. Kidney Int 2010;77:292–298.
  13. Gutiérrez OM: Fibroblast growth factor-23 and disordered vitamin D metabolism in chronic kidney disease: updating the ‘trade-off’ hypothesis. Clin J Am Soc Nephrol 2010;5:1710–1716.
  14. Shigematsu T, Yamashita T, Fukumoto S, et al: Possible involvement of circulating fibroblast growth factor-23 in the development of secondary hyperparathyroidism associated with renal insufficiency. Am J Kidney Dis 2004;44:250–256.
  15. Gutierrez O, Isakova T, Rhee E, et al: Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 2005;16:2205–2215.
  16. Nishi H, Nii-Kono T, Nakanishi S, et al: Intravenous calcitriol therapy increases serum concentration of fibroblast growth factor-23 in dialysis patients with secondary hyperparathyroidism. Nephron Clin Pract 2005;101:c94–c99.
  17. Nakanishi S, Kazama JJ, Nii-Kono T, et al: Serum fibroblast factor-23 levels predict the future refractory hyperparathyroidism in dialysis patients. Kidney Int 2005;67:1171–1178.
  18. Kazama JJ, Sato F, Omori K, et al: Pretreatment serum FGF23 levels predict the efficacy of calcitriol therapy in dialysis patients. Kidney Int 2005;67:1120–1125.
  19. Gutierrez OM, Mannstadt M, Isakova T, et al: Fibroblast growth factor-23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008;359:584–592.
  20. Jean G, Terrat JC, Vanel T, et al: High levels of serum fibroblast growth factor-23 are associated with increased mortality in long haemodialysis patients. Nephrol Dial Transplant 2009;24:2792–2796.
  21. Shimizu Y, Tada Y, Yamauchi M, et al: Hypophosphatemia induced by intravenous administration of saccharated ferric oxide: another form of FGF23-related hypophosphatemia. Bone 2009;45:814–816.
  22. Schouten BJ, Hunt PJ, Livesey JH, et al: FGF23 elevation and hypophosphatemia after intravenous iron polymaltose: a prospective study. J Clin Endocrinol Metab 2009;94:2332–2337.
  23. Fishbane S, Maesaka JK: Iron management in end-stage renal disease. Am J Kidney Dis 1997;29:319–333.
  24. Rozen-Zvi B, Gafter-Gvili A, Paul M, Leibovici L, Shpilberg O, Gafter U: Intravenous versus oral iron supplementation for the treatment of anemia in CKD: systematic review and meta-analysis. Am J Kidney Dis 2008;52:897–906.
  25. Payne RB, Little AJ, Williams RB, Milner JR: Interpretation of serum calcium levels in patients with abnormal serum proteins. Br Med J 1973;4:643–646.
  26. Okada M, Imamura K, Fuchigami T, et al: Two cases of nonspecific multiple ulcers of the small intestine associated with osteomalacia caused by long-term intravenous administration of saccharated ferric oxide (in Japanese). Nippon Naika Gakkai Zasshi 1982;71:1566–1572.
  27. Okada M, Imamura K, Iida M, et al: Hypophosphatemia induced by intravenous administration of saccharated iron oxide. Klin Wochenschr 1983;61:99–102.
  28. Sato K, Shiraki M: Saccharated ferric oxide-induced osteomalacia in Japan: iron-induced osteopathy due to nephropathy. Endocr J 1998;45:431–439.
  29. Ishii K, Fumoto T, Iwai K, et al: Coordination of PGC-1β and iron uptake in mitochondrial biogenesis and osteoclast activation. Nat Med 2009;15:259–266.
  30. Liu S, Guo R, Simpson LG, Xiao ZS, Burnham CE, Quarles LD: Regulation of fibroblastic growth factor 23 expression but not degradation by PHEX. J Biol Chem 2003;278:37419–37426.
  31. Komaba H, Goto S, Fujii H, et al: Depressed expression of Klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients. Kidney Int 2010;77:232–238.
  32. Kumata C, Mizobuchi M, Ogata H, et al: Involvement of α-Klotho and fibroblast growth factor receptor in the development of secondary hyperparathyroidism. Am J Nephrol 2010;31:230–238.
  33. Galitzer H, Ben-Dov IZ, Silver J, et al: Parathyroid cell resistance to fibroblast growth factor-23 in secondary hyperparathyroidism of chronic kidney disease. Kidney Int 2010;77:211–218.
  34. Canalejo R, Canalejo A, Martinez-Moreno JM, et al: FGF23 fails to inhibit uremic parathyroid glands. J Am Soc Nephrol 2010;21:1125–1135.


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