Skip to main content

Dietary phosphorus restriction by a standard low-protein diet decreased serum fibroblast growth factor 23 levels in patients with early and advanced stage chronic kidney disease

Clinical and Experimental Nephrology volume 18, pages 925–931 (2014)Cite this article

Abstract

Background

Elevated serum fibroblast growth factor 23 (FGF23) levels are associated with mortality, cardiovascular disease, and disease progression in patients with chronic kidney disease (CKD). Although recent studies demonstrated that FGF23 levels decreased in response to dietary restriction of phosphorus and/or use of phosphate binders, research on the effects of a standard low-protein diet is lacking.

Methods

The effects of a standard low-protein diet on serum FGF23, intact parathyroid hormone, and 1,25-dihydroxyvitamin D levels were investigated in patients with early (n = 15) and advanced (n = 20) CKD.

Results

Serum FGF23 levels decreased in both groups. Changes in FGF23 levels correlated with changes in 24 h urinary phosphorus excretion in the advanced CKD group. Decreased serum intact parathyroid hormone levels were observed only in the advanced CKD group and increased serum 1,25-dihydroxyvitamin D levels only in the early CKD group.

Conclusions

These findings suggest that consuming standard low-protein diet decreased serum FGF23 levels in patients with CKD. Serum FGF23 levels may therefore be a useful marker to monitor the effects of a low-protein diet in early and advanced stage CKD.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

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.

    PubMed Central  PubMed  Article  Google Scholar 

  2. Isakova T, Xie H, Yang W, Xie D, et al. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA. 2011;305:2432–49.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  3. Jean G, Terrat JC, Vanel T, et al. High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients. Nephrol Dial Transpl. 2009;24:2792–6.

    CAS  Article  Google Scholar 

  4. Kendrick J, Cheung AK, Kaufman JS, et al. FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis. J Am Soc Nephrol. 2011;22:1913–22.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  5. Seiler S, Reichart B, Roth D, Seibert E, Fliser D, Heine GH. FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment. Nephrol Dial Transpl. 2010;25:3983–9.

    CAS  Article  Google Scholar 

  6. Nakano C, Hamano T, Fujii N, et al. Intact fibroblast growth factor 23 levels predict incident cardiovascular event before but not after the start of dialysis. Bone. 2012;50:1266–74.

    CAS  PubMed  Article  Google Scholar 

  7. Fliser D, Kollerits B, Neyer U, et al. 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.

    CAS  PubMed  Article  Google Scholar 

  8. Titan SM, Zatz R, Graciolli FG, et al. FGF-23 as a predictor of renal outcome in diabetic nephropathy. Clin J Am Soc Nephrol. 2011;6:241–7.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  9. Nakano C, Hamano T, Fujii N, et al. Combined use of vitamin D status and FGF23 for risk stratification of renal outcome. Clin J Am Soc Nephrol. 2012;7:810–9.

    CAS  PubMed  Article  Google Scholar 

  10. Faul C, Amaral AP, Oskouei B, et al. FGF23 induces left ventricular hypertrophy. J Clin Invest. 2011;121:4393–408.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  11. Ferrari SL, Bonjour JP, Rizzoli R. Fibroblast growth factor-23 relationship to dietary phosphate and renal phosphate handling in healthy young men. J Clin Endocrinol Metab. 2005;90:1519–24.

    CAS  PubMed  Article  Google Scholar 

  12. Burnett SM, Gunawardene SC, Bringhurst FR, Jüppner H, Lee H, Finkelstein JS. Regulation of C-terminal and intact FGF-23 by dietary phosphate in men and women. J Bone Miner Res. 2006;21:1187–96.

    CAS  PubMed  Article  Google Scholar 

  13. Antoniucci DM, Yamashita T, Portale AA. Dietary phosphorus regulates serum fibroblast growth factor-23 concentrations in healthy men. J Clin Endocrinol Metab. 2006;91:3144–9.

    CAS  PubMed  Article  Google Scholar 

  14. Sigrist M, Tang M, Beaulieu M, et al. Responsiveness of FGF-23 and mineral metabolism to altered dietary phosphate intake in chronic kidney disease (CKD): results of a randomized trial. Nephrol Dial Transpl. 2013;28:161–9.

    CAS  Article  Google Scholar 

  15. Gonzalez-Parra E, Gonzalez-Casaus ML, Galán A, et al. Lanthanum carbonate reduces FGF23 in chronic kidney disease Stage 3 patients. Nephrol Dial Transpl. 2011;26:2567–71.

    CAS  Article  Google Scholar 

  16. 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.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  17. 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.

    CAS  PubMed  Article  Google Scholar 

  18. Di Iorio B, Di Micco L, Torraca S, et al. Acute effects of very-low-protein diet on FGF23 levels: a randomized study. Clin J Am Soc Nephrol. 2012;7:581–7.

    PubMed  Article  Google Scholar 

  19. 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 Transpl. 2012;27:1050–4.

    CAS  Article  Google Scholar 

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

    CAS  PubMed  Article  Google Scholar 

  21. Bleskestad IH, Bergrem H, Hartmann A, Godang K, Gøransson LG. Fibroblast growth factor 23 and parathyroid hormone after treatment with active vitamin D and sevelamer carbonate in patients with chronic kidney disease stage 3b, a randomized crossover trial. BMC Nephrol. 2012;13:49.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  22. Isakova T, Gutiérrez OM, Smith K, et al. Pilot study of dietary phosphorus restriction and phosphorus binders to target fibroblast growth factor 23 in patients with chronic kidney disease. Nephrol Dial Transpl. 2011;26:584–91.

    CAS  Article  Google Scholar 

  23. Saito H, Maeda A, Ohtomo S, et al. Circulating FGF-23 is regulated by 1α, 25-dihydroxyvitamin D3 and phosphorus in vivo. J Biol Chem. 2005;280:2543–9.

    CAS  PubMed  Article  Google Scholar 

  24. Ito M, Sakai Y, Furumoto M, et al. Vitamin D and phosphate regulate fibroblast growth factor-23 in K-562 cells. Am J Physiol Endocrinol Metab. 2005;288:E1101–9.

    CAS  PubMed  Article  Google Scholar 

  25. Matsuo S, Imai E, Horio M, et al. Collaborators developing the Japanese equation for estimated GFR: revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.

    CAS  PubMed  Article  Google Scholar 

  26. Payne RB, Little AJ, Williams RB, Milner JR. Interpretation of serum calcium levels in patients with abnormal serum proteins. BMJ. 1973;4:643–6.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

  27. Calvo MS, Park YK. Changing phosphorus content of the US diet: potential for adverse effects on bone. J Nutr. 1996;126:1168S–80S.

    CAS  PubMed  Google Scholar 

  28. Liu S, Tang W, Zhou J, et al. Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. J Am Soc Nephrol. 2006;17:1305–15.

    CAS  PubMed  Article  Google Scholar 

  29. Isakova T, Gutierrez O, Shah A, et al. Postprandial mineral metabolism and secondary hyperparathyroidism in early CKD. J Am Soc Nephrol. 2007;19:615–23.

    Article  Google Scholar 

  30. Nishida Y, Taketani Y, Yamanaka-Okumura H, et al. Acute effect of oral phosphate loading on serum fibroblast growth factor 23 levels in healthy men. Kidney Int. 2006;70:2141–7.

    CAS  PubMed  Google Scholar 

  31. Ito N, Fukumoto S, Takeuchi Y, et al. Effect of acute changes of serum phosphate on fibroblast growth factor (FGF) 23 levels in humans. J Bone Miner Metab. 2007;25:419–22.

    CAS  PubMed  Article  Google Scholar 

  32. 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.

    PubMed Central  PubMed  Article  Google Scholar 

  33. Ben-Dov IZ, Galitzer H, Lavi-Moshayoff V, et al. The parathyroid is a target organ for FGF23 in rats. J Clin Invest. 2007;117:4003–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Lavi-Moshayoff V, Wasserman G, Meir T, et al. PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop. Am J Physiol Renal Physiol. 2010;299:F882–9.

    CAS  PubMed  Article  Google Scholar 

  35. Shigematsu T, Kazama JJ, Yamashita T, et al. Possible involvement of circulating fibroblast factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency. Am J Kidney Dis. 2004;44:250–6.

    CAS  PubMed  Article  Google Scholar 

  36. Moe SM, Zidehsarai MP, Chambers MA, et al. Vegetarian compared with meat dietary protein source and phosphorus homeostasis in chronic kidney disease. Clin J Am Soc Nephrol. 2011;6:257–64.

    CAS  PubMed Central  PubMed  Article  Google Scholar 

Download references

Acknowledgments

This study is supported by the Himeji Nephrology Research Grant and a grant from The Kidney Foundation, Japan (JKFB12-43). Preliminary results of this study were presented in part at the American Society of Nephrology Kidney Week 2013 Annual Meeting in Atlanta, GA, USA, on November 8, 2013.

Conflict of interest

The authors declare that no conflicts of interest exist.

Author information

Affiliations

  1. Division of Nephrology and Kidney Center, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan

    Shunsuke Goto, Kentaro Nakai, Keiji Kono, Yuriko Yonekura, Jun Ito, Hideki Fujii & Shinichi Nishi

Authors
  1. Shunsuke Goto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kentaro Nakai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Keiji Kono
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuriko Yonekura
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jun Ito
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hideki Fujii
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shinichi Nishi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hideki Fujii.

About this article

Cite this article

Goto, S., Nakai, K., Kono, K. et al. Dietary phosphorus restriction by a standard low-protein diet decreased serum fibroblast growth factor 23 levels in patients with early and advanced stage chronic kidney disease. Clin Exp Nephrol 18, 925–931 (2014). https://doi.org/10.1007/s10157-014-0947-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-014-0947-4

Keywords

  • Chronic kidney disease
  • Fibroblast growth factor 23
  • Protein restriction