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The relationship between circulating fibroblast growth factor 23 and bone metabolism factors in Korean hemodialysis patients

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Abstract

Background

Fibroblast growth factor 23 (FGF-23) is a circulating factor that acts as a phosphaturic factor in the kidneys. It is also involved in several disorders of phosphate regulation and bone metabolism. We hypothesized that increased FGF-23 levels in patients with endstage renal disease (ESRD) on maintenance hemodialysis would be associated with increased bone demineralization, and we analyzed the relationship between FGF-23 levels and bone mineral density (BMD).

Methods

The serum level of FGF-23 was measured in this cross-sectional study, whose subjects consisted of 54 patients with ESRD on maintenance hemodialysis. Clinical parameters associated with hemodialysis and bone metabolism were measured. The relationship between serum FGF-23 and BMD and the factors affecting the serum level of FGF-23 were analyzed.

Results

Serum FGF-23 levels were significantly higher in ESRD patients on maintenance hemodialysis than in normal persons (2961.4 vs. 30 pg/ml). Multiple regression analysis showed that increasing FGF-23 levels were associated with serum phosphate (r = 0.684, P < 0.001), but not with BMD or other bone metabolism factors. Factors affecting log10FGF-23 included the serum calcium phosphate product (β = 0.603) and K t/V (integrated fractional clearance expressed per dialysis, β = −0.244). These results were also seen in an analysis of the correlations based on T score or gender.

Conclusions

FGF-23 levels were positively associated with serum phosphate levels but were not correlated with BMD. The only factors affecting log10FGF-23 were the serum calcium phosphate product and K t/V. These findings suggest that FGF-23 may have no direct effect on bone mineralization, and further studies are warranted to examine the effects of FGF-23 on vitamin D metabolism.

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References

  1. 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.

    Article  CAS  PubMed  Google Scholar 

  2. Weber TJ, Liu S, Indridason OS, Quarles LD. Serum FGF23 levels in normal and disordered phosphorus homeostasis. J Bone Miner Res. 2003;18:1227–34.

    Article  CAS  PubMed  Google Scholar 

  3. Imanishi Y, Inaba M, Nakatsuka K, Nagasue K, Okuno S, Yoshihara A, et al. FGF-23 in patients with end-stage renal disease on hemodialysis. Kidney Int. 2004;65:1943–6.

    Article  CAS  PubMed  Google Scholar 

  4. Mirams M, Robinson BG, Mason RS, Nelson AE. Bone as a source of FGF23: regulation by phosphate? Bone. 2004;35:1192–9.

    Article  CAS  PubMed  Google Scholar 

  5. Liu S, Zhou J, Tang W, Jiang X, Rowe DW, Quarles LD. Pathogenic role of FGF23 in Hyp mice. Am J Physiol Endocrinol Metab. 2006;291:E38–49.

    Article  CAS  PubMed  Google Scholar 

  6. Sitara D, Razzaque MS, Hesse M, Yoganathan S, Taguchi T, Erben RG, et al. Homozygous ablation of fibroblast growth factor-23 results in hyperphosphatemia and impaired skeletogenesis, and reverses hypophosphatemia in Phex-deficient mice. Matrix Biol. 2004;23:421–32.

    Article  CAS  PubMed  Google Scholar 

  7. Saito H, Kusano K, Kinosaki M, Kinosaki M, Ito H, Hirata M, et al. Human fibroblast growth factor-23 mutants suppress Na+-dependent phosphate co-transport activity and 1alpha,25-dihydroxyvitamin D3 production. J Biol Chem. 2003;278:2206–11.

    Article  CAS  PubMed  Google Scholar 

  8. Inoue Y, Segawa H, Kaneko I, Yamanaka S, Kusano K, Kawakami E, et al. Role of the vitamin D receptor in FGF23 action on phosphate metabolism. Biochem J. 2005;390:325–31.

    Article  CAS  PubMed  Google Scholar 

  9. Baum M, Schiavi S, Dwarakanath V, Quigley R. Effect of fibroblast growth factor-23 on phosphate transport in proximal tubules. Kidney Int. 2005;68:1148–53.

    Article  CAS  PubMed  Google Scholar 

  10. Shimada T, Yamazaki Y, Takahashi M, Hasegawa H, Urakawa I, Oshima T, 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 

  11. Kuro OM. Klotho as a regulator of fibroblast growth factor signaling and phosphate/calcium metabolism. Curr Opin Nephrol Hypertens. 2006;15:437–41.

    Article  Google Scholar 

  12. National Kidney Foundation. K/DOQI clinical practice guidelines for hemodialysis adequacy, 2000. Am J Kidney Dis. 2001;37(Suppl 1):S7–64.

    Google Scholar 

  13. Marsell R, Mirza MAI, Mallmin H, Karlsson M, Mellström D, Orwoll E, et al. Relation between fibroblast growth factor-23, body weight and bone mineral density in elderly men. Osteoporos Int. 2009;20:1167–73.

    Article  CAS  PubMed  Google Scholar 

  14. Portale AA, Booth BE, Halloran BP, Morris RC Jr. Effect of dietary phosphorus on circulating concentrations of 1,25-dihydroxyvitamin D and immunoreactive parathyroid hormone in children with moderate renal insufficiency. J Clin Invest. 1984;73:1580–9.

    Article  CAS  PubMed  Google Scholar 

  15. Nagano N, Miyata S, Abe M, Kobayashi N, Wakita S, Yamashita T, et al. Effect of manipulating serum phosphorus with phosphate binder on circulating PTH and FGF23 in renal failure rats. Kidney Int. 2006;69:531–7.

    Article  CAS  PubMed  Google Scholar 

  16. Khachigian LM. Early growth response-1 in cardiovascular pathobiology. Circ Res. 2006;98:186–91.

    Article  CAS  PubMed  Google Scholar 

  17. Qunibi WY, Abouzahr F, Mizani MR, Nolan CR, Arya R, Hunt KJ. Cardiovascular calcification in Hispanic Americans (HA) with chronic kidney disease (CKD) due to type 2 diabetes. Kidney Int. 2005;68:271–7.

    Article  PubMed  Google Scholar 

  18. Mehrotra R. Disordered mineral metabolism and vascular calcification in nondialyzed chronic kidney disease patients. J Ren Nutr. 2006;16:100–8.

    Article  PubMed  Google Scholar 

  19. Larsson T, Nisbeth U, Ljunggren Ö, Jüppner H, Jonsson KB. Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers. Kidney Int. 2003;64:2272–9.

    Article  CAS  PubMed  Google Scholar 

  20. Gutierrez O, Isakova T, Rhee E, Shah A, Holmes J, Collerone G, et al. Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol. 2005;16:2205–15.

    Article  CAS  PubMed  Google Scholar 

  21. Shigematsu T, Kazama JJ, Yamashita T, Fukumoto S, Hosoya T, Gejyo F, 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;44:250–6.

    Article  CAS  PubMed  Google Scholar 

  22. Torres PU, Friedlander G, Vernejoul MC, Silve C, Prié D. Bone mass does not correlate with the serum fibroblast growth factor 23 in hemodialysis patients. Kidney Int. 2008;73:102–7.

    Article  Google Scholar 

  23. Stubbs J, Liu S, Quarles LD. Role of fibroblast growth factor 23 in phosphate homeostasis and pathogenesis of disordered mineral metabolism in chronic kidney disease. Semin Dial. 2007;20:302–8.

    Article  PubMed  Google Scholar 

  24. Gutiérrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, et al. Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008;359:584–92.

    Article  PubMed  Google Scholar 

  25. Sitara D, Kim S, Razzaque, Bergwitz C, Taguchi T, Schüler C, et al. Genetic evidence of serum phosphate-independent functions of FGF-23 on bone. PLoS Genet. 2008;4:e1000154.

    Article  PubMed  Google Scholar 

  26. Stubbs JR, Liu S, Tang W, Zhou J, Wang Y, Yao X, et al. Role of hyperphosphatemia and 1,25 dihydroxyvitamin D in vascular calcification and mortality in fibroblastic growth factor 23 null mice. J Am Soc Nephrol. 2007;18:2116–24.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Nephrology, Kyung Hee University School of Medicine, 1 Heogi-Dong, Dongdaemun-Gu, Seoul, 130-701, Korea

    So-Youn Park, Kyung-Hwan Jeong, Ju-Young Moon, Sang-Ho Lee, Chun-Gyoo Ihm & Tae-Won Lee

  2. Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Seoul, Korea

    Sang Youl Rhee & Jeong-Taek Woo

  3. Department of Preventive Medicine, Kyung Hee University School of Medicine, Seoul, Korea

    In-Hwan Oh

Authors
  1. So-Youn Park
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  2. Kyung-Hwan Jeong
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  9. Tae-Won Lee
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Correspondence to Tae-Won Lee.

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Park, SY., Jeong, KH., Moon, JY. et al. The relationship between circulating fibroblast growth factor 23 and bone metabolism factors in Korean hemodialysis patients. Clin Exp Nephrol 14, 239–243 (2010). https://doi.org/10.1007/s10157-010-0272-5

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  • DOI: https://doi.org/10.1007/s10157-010-0272-5

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