Skip to main content
SpringerLink
Log in

Effects of lanthanum carbonate and calcium carbonate on fibroblast growth factor 23 and hepcidin levels in chronic hemodialysis patients

  • Original article
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

An Erratum to this article was published on 23 February 2017

This article has been updated

Abstract

Background

Phosphate binders have an impact on fibroblast growth factor 23 (FGF23); however, the effect of phosphate binders on serum hepcidin has not been explored. We conducted a 24-week multicenter randomized controlled trial to investigate the effects of lanthanum carbonate or calcium carbonate monotherapy on serum phosphate, FGF23, and hepcidin levels in chronic hemodialysis patients.

Methods

Forty-six patients were recruited, and daily dietary phosphorus was controlled between 600–800 mg. Serum calcium, phosphate, albumin, alkaline phosphatase (ALP), FGF23, intact parathyroid hormone (iPTH), hepcidin, high-sensitivity CRP (hsCRP), 25(OH)D, 1,25(OH)2D, fetuin-A, and osteopontin were checked as scheduled.

Results

Twenty-five patients completed the study. Mean serum FGF23 level was significantly decreased after a 24-week treatment with lanthanum (8677.5 ± 7490.0 vs. 4692.8 ± 5348.3 pg/mL, p = 0.013, n = 13), but not with calcium (n = 12). The reduction of serum hepcidin in lanthanum group was positively correlated with the decrement of serum phosphate (r = 0.631, p = 0.021) and serum hsCRP (r = 0.670, p = 0.012) levels, respectively. Serum ALP, iPTH, vitamin D, fetuin-A, and osteopontin revealed no significant inter- or intragroup differences.

Conclusions

In summary, a decrease in serum FGF23 levels and a trend of decline in hepcidin levels were observed only in lanthanum group.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Change history

  • 23 February 2017

    An erratum to this article has been published.

References

  1. Gutiérrez OM, Mannstadt M, Isakova T, et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008;359:584–92.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Gutiérrez OM, Januzzi JL, Isakova T, et al. Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation. 2009;119:2545–52.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Mirza MA, Larsson A, Lind L, et al. Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis. 2009;205:385–90.

    Article  CAS  PubMed  Google Scholar 

  4. Mirza MA, Hansen T, Johansson L, et al. Relationship between circulating FGF23 and total body atherosclerosis in the community. Nephrol Dial Transplant. 2009;24:3125–31.

    Article  CAS  PubMed  Google Scholar 

  5. Gonzalez-Parra E, Gonzalez-Casaus ML, Galán A, et al. Lanthanum carbonate reduces FGF 23 in chronic kidney disease stage 3 patients. Nephrol Dial Transplant. 2011;26:2567–71.

    Article  CAS  PubMed  Google Scholar 

  6. Isakova T, Barchi-Chung A, Enfield G, et al. Effects of diet phosphate restriction and phosphate binders on FGF23 levels in CKD. Clin J Am Soc Nephrol. 2013;8:1009–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yilmaz MI, Sonmez A, Saglam M, et al. Comparison of calcium acetate and sevelamer on vascular function and fibroblast growth factor 23 in CKD patients: a randomized clinical trial. Am J Kidney Dis. 2012;59:177–85.

    Article  CAS  PubMed  Google Scholar 

  8. Oliveira RB, Cancela AL, Graciolli FG, et al. Early control of PTH and FGF23 in normophosphatemic CKD patients: a new target in CKD-MBD therapy? Clin J Am Soc Nephrol. 2010;5:286–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Soriano S, Ojeda R, Rodríguez M, et al. The effect of phosphate binders, calcium and lanthanum carbonate on FGF23 levels in chronic kidney disease patients. Clin Nephrol. 2013;80:17–22.

    Article  CAS  PubMed  Google Scholar 

  10. Koiwa F, Kazama JJ, Tokumoto A, et al. Sevelamer hydrochloride and calcium bi-carbonate reduce serum fibroblast growth factor 23 levels in dialysis patients. Ther Apher Dial. 2005;9:336–9.

    Article  CAS  PubMed  Google Scholar 

  11. Spatz C, Roe K, Lehman E, et al. Effect of a non-calcium-based phosphate binder on fibroblast growth factor 23 in chronic kidney disease. Nephron Clin Prac. 2013;123:61–6.

    Article  CAS  Google Scholar 

  12. Brandenberg VM, Schlieper G, Heussen N, et al. Serological cadiovascular and mortality risk predictors in dialysis patients receiving sevelamer: a prospective study. Nephrol Dial Transplant. 2010;25:2672–9.

    Article  Google Scholar 

  13. Shigematsu T. Negi S; COLC Research Group. Combined therapy with lanthanum carbonate and calcium carbonate for hyperphosphatemia decreases serum FGF-23 level independently of calcium and PTH (COLC Study). Nephrol Dial Transplant. 2012;27:1050–4.

    Article  CAS  PubMed  Google Scholar 

  14. Cancela AL, Oliveira RB, Graciolli FG, et al. Fibroblast growth factor 23 in hemodialysis patients: effects of phosphate binder, calcitriol and calcium concentration in the dialysate. Nephron Clin Pract. 2011;117:c74–82.

    Article  CAS  PubMed  Google Scholar 

  15. Toida T, Fukudome K, Fujimoto S, et al. Effect of lanthanum carbonate vs. calcium carbonate on serum calcium in hemodialysis patients: a crossover study. Clin Nephrol. 2012;78:216–23.

    Article  CAS  PubMed  Google Scholar 

  16. Yusuf AA, Weinhandl ED, St Peter WL. Comparative effectiveness of calcium acetate and sevelamer on clinical outcomes in elderly hemodialysis patients enrolled in Medicare part D. Am J Kidney Dis. 2014;64:95–103.

    Article  CAS  PubMed  Google Scholar 

  17. Jamal SA, Vandermeer B, Raggi P, et al. Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis. Lancet. 2013;382:1268–77.

    Article  CAS  PubMed  Google Scholar 

  18. Ganz T. Molecular control of iron transport. J Am Soc Nephrol. 2007;18:394–400.

    Article  CAS  PubMed  Google Scholar 

  19. Young B, Zaritsky J. Hepcidin for clinicians. Clin J Am Soc Nephrol. 2009;4:1384–7.

    Article  CAS  PubMed  Google Scholar 

  20. Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood. 2003;102:783–8.

    Article  CAS  PubMed  Google Scholar 

  21. Carvalho C, Isakova T, Collerone G, et al. Hepcidin and disordered mineral metabolism in chronic kidney disease. Clin Nephrol. 2011;76:90–8.

    Article  CAS  PubMed  Google Scholar 

  22. Samouilidou E, Pantelias K, Petras D, et al. Serum hepcidin levels are associated with serum triglycerides and interleukin-6 concentrations in patients with end-stage renal disease. Ther Apher Dial. 2014;18:279–83.

    CAS  PubMed  Google Scholar 

  23. Shimada T, Yamazaki Y, Takahashi M, et al. Vitamin D receptor-independent FGF23 actions in regulating phosphate and vitamin D metabolism. Am J Physiol Renal Physiol. 2005;289:F1088–95.

    Article  CAS  PubMed  Google Scholar 

  24. Kobayashi K, Imanishi Y, Miyauchi A, et al. Regulation of plasma fibroblast growth factor 23 by calcium in primary hyperparathyroidism. Eur J Endocrinol. 2006;154:93–9.

    Article  CAS  PubMed  Google Scholar 

  25. David V, Dai B, Martin A, et al. Calcium regulates FGF-23 expression in bone. Endocrinology. 2013;154:4469–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Rodriquez-Ortiz ME, Lopez I, Muñoz-Castañeda JR, et al. Calcium deficiency reduces circulating levels of FGF23. J Am Soc Nephrol. 2012;23:1190–7.

    Article  Google Scholar 

  27. Caglar K, Yilmaz MI, Saglam M, et al. Short-term treatment with sevelamer increases serum fetuin-A concentration and improves endothelial dysfunction in chronic kidney disease stage 4 patients. Clin J Am Soc Nephrol. 2008;3:61–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Zhou YB, Jin SJ, Cai Y, et al. Lanthanum acetate inhibits vascular calcification induced by vitamin D3 plus nicotine in rats. Exp Biol Med. 2009;234:908–17.

    Article  CAS  Google Scholar 

  29. El-Abbadi MM, Pai AS, Leaf EM, et al. Phosphate feeding induces arterial medial calcification in uremic mice: role of serum phosphorus, fibroblast growth factor-23, and osteopontin. Kidney Int. 2009;75:1297–307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. D’Haese PC, Spasovski GB, Sikole A, et al. A multicenter study on the effects of lanthanum carbonate (Fosrenol) and calcium carbonate on renal bone disease in dialysis patients. Kidney Int. 2003;63(Suppl 85):S73–8.

    Article  Google Scholar 

  31. Manabe R, Fukami K, Ando R, et al. Effects of switching from calcium carbonate to lanthanum carbonate on bone mineral metabolism in hemodialysis patients. Ther Apher Dial. 2013;17(Suppl 1):35–40.

    Article  CAS  PubMed  Google Scholar 

  32. Guo F, Guo X, Xie A, et al. The suppressive effects of lanthanum on the production of inflammatory mediators in mice challenged by LPS. Biol Trace Elem Res. 2011;142:693–703.

    Article  CAS  PubMed  Google Scholar 

  33. Navarro-González JF, Mora-Fernández C, Muros M, et al. Mineral metabolism and inflammation in chronic kidney disease patients: a cross-sectional study. Clin J Am Soc Nephrol. 2009;4:1646–54.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Nicolas G, Bennoun M, Devaux I, et al. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci USA. 2001;98:8780–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Lesbordes-Brion JC, Viatte L, Bennoun M, et al. Targeted disruption of the hepcidin 1 gene results in severe hemochromatosis. Blood. 2006;108:1402–5.

    Article  CAS  PubMed  Google Scholar 

  36. Takeda Y, Komaba H, Goto S, et al. Effect of intravenous saccharated ferric oxide on serum FGF23 and mineral metabolism in hemodialysis patients. Am J Nephrol. 2011;33:421–6.

    Article  CAS  PubMed  Google Scholar 

  37. Braithwaite V, Prentice AM, Doherty C, et al. FGF23 is correlated with iron status but not with inflammation and decreases after iron supplementation: a supplementation study. Int J Pediatr Endocrinol. 2012;2012:27.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Deger SM, Erten Y, Pasaoglu OT, et al. The effects of iron on FGF23-mediated Ca-P metabolism in CKD patients. Clin Exp Nephrol. 2013;17:416–23.

    Article  CAS  PubMed  Google Scholar 

  39. Gravesen E, Hofman-Bang J, Mace ML, et al. High dose intravenous iron, mineral homeostasis and intact FGF23 in normal and uremic rats. BMC Nephrol. 2013;14:281.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Lin HH, Liou HH, Wu MS, et al. Long-term sevelamer treatment lowers serum fibroblast growth factor 23 accompanied with increasing serum Klotho levels in chronic haemodialysis patients. Nephrology. 2014;19:672–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The research was supported by Saint Mary’s Hospital Research Fund. (SMHRF100004).

Author information

Author notes

    Authors and Affiliations

    1. Division of Nephrology, of Internal Medicine, Department Saint Mary’s Hospital Luodong, Yilan, Taiwan

      Yu-Ming Chang, Shih-Ching Tsai, Chih-Chung Shiao, Jsun-Liang Kao & Rong-Na Jhen

    2. Division of Nephrology, Department of Internal Medicine, Hsin-Jen Hospital, 5th F, 387 Chong-Cheng Road, Xinzhuang District, 242, New Taipei City, Taiwan

      Hung-Hsiang Liou

    3. Department of Nursing, Saint Mary’s Hospital Luodong, Yilan, Taiwan

      Chuan-Lan Yang, Kua-Sui Hsu, I-Ling Chen & Ya-Ting Huang

    4. Nutrition Room, Saint Mary’s Hospital Luodong, Yilan, Taiwan

      Nai-Yu Tung

    5. Dialysis Center, Hsin-Ren Clinics, New Taipei City, Taiwan

      Hung-Hsiang Liou & Mei-Chyn Liu

    Authors
    1. Yu-Ming Chang
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Shih-Ching Tsai
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Chih-Chung Shiao
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Hung-Hsiang Liou
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Chuan-Lan Yang
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Nai-Yu Tung
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Kua-Sui Hsu
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. I-Ling Chen
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Mei-Chyn Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Jsun-Liang Kao
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Rong-Na Jhen
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Ya-Ting Huang
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Hung-Hsiang Liou.

    Ethics declarations

    Conflict of interest

    The authors have declared that no conflict of interest exists.

    Human rights and ethical approval

    All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee at which the studies were conducted (IRB approval number SMHIRB100001) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

    Informed consent

    Informed consent was obtained from all individual participants included in the study.

    Additional information

    Registration of clinical trials The registration number of NCT01845090 in www.clinicaltrials.gov. (Clinical Trials).

    Y.-M. Chang, S.-C. Tsai, and H.-H. Liou contribute equally.

    An erratum to this article is available at https://doi.org/10.1007/s10157-017-1384-y.

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Chang, YM., Tsai, SC., Shiao, CC. et al. Effects of lanthanum carbonate and calcium carbonate on fibroblast growth factor 23 and hepcidin levels in chronic hemodialysis patients. Clin Exp Nephrol 21, 908–916 (2017). https://doi.org/10.1007/s10157-016-1362-9

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s10157-016-1362-9

    Keywords

    Search

    Navigation