International Urology and Nephrology

, Volume 46, Issue 1, pp 99–106 | Cite as

Relationship between serum fibroblast growth factor-23 level and mortality in chronic hemodialysis patients

  • Himiko Sugimoto
  • Tetsuya Ogawa
  • Yuko Iwabuchi
  • Kuniaki Otsuka
  • Kosaku Nitta
Nephrology - Original Paper



Fibroblast growth factor-23 (FGF23) is a phosphate-regulating hormone and is found to be markedly increased in patients with chronic kidney disease. The aim of the present study was to evaluate the relationship between serum FGF23 levels and mortality, including the impact of gender and cardiovascular disease (CVD), in a Japanese cohort of chronic hemodialysis (HD) patients.


Ninety-two maintenance dialysis patients (58 men; mean age 60.3 years) were included. Serum intact FGF23, calcium, phosphate, albumin, intact parathyroid hormone (PTH), and C-reactive protein were measured at baseline. CVD was defined as clinical symptoms and/or a history of CVD.


During a median follow-up time of 53.2 months, 24 patients (26 %) died. Serum FGF23 levels were positively correlated with serum levels of calcium (r = 0.5433, P < 0.0001), phosphate (r = 0.5048, P < 0.0001), calcium × phosphate product (r = 0.6801, P < 0.0001), and intact PTH (r = 0.2710, P = 0.0090) (r = 0.27, P < 0.0001). In Cox proportional hazard models, serum FGF23 level was not associated with increased mortality risk, neither in crude nor in multivariate-adjusted models. However, in a subgroup analysis of women with previous CVD, serum FGF23 level above median was associated with higher cardiovascular event risk in crude models (hazard ratio 9.52, 95 % confidence interval 1.56–86.11, P = 0.0129). Kaplan–Meier analysis stratifying for the presence of CVD demonstrated a significant higher mortality risk in patients with history of CVD and higher serum FGF23 levels (P < 0.0001).


Serum FGF23 level was not associated with increased mortality risk in this cohort of prevalent HD patients. These results suggest that the impact of FGF23 on mortality may be modified by gender and previous CVD and is blunted in the grade of hyperphosphatemia.


Chronic kidney disease Hemodialysis Fibroblast growth factor-23 Mortality Cardiovascular disease 


  1. 1.
    Yamashita T, Yoshioka M, Itoh N (2000) Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain. Biochem Biophys Res Commun 277:494–498PubMedCrossRefGoogle Scholar
  2. 2.
    Moe S, Drueke T, Cunningham J et al (2006) Definition, evaluation, and classification of renal osteodystrophy: a position statement from kidney disease: improving global outcomes (KDIGO). Kidney Int 69:1945–1953PubMedCrossRefGoogle Scholar
  3. 3.
    Park SY, Jeong KH, Moon JY et al (2010) The relationship between circulating fibroblast growth factor 23 and bone metabolism factors in Korean hemodialysis patients. Clin Exp Nephrol 14:239–243PubMedCrossRefGoogle Scholar
  4. 4.
    Yamashita T, Konishi M, Miyake A et al (2002) Fibroblast growth factor (FGF)-23 inhibits renal phosphate reabsorption by activation of the mitogen-activated protein kinase pathway. J Biol Chem 277:28265–28270PubMedCrossRefGoogle Scholar
  5. 5.
    Shimada T, Urakawa I, Yamazaki Y et al (2004) FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa. Biochem Biophys Res Commun 314:409–414PubMedCrossRefGoogle Scholar
  6. 6.
    Krajisnik T, Bjorklund P, Marsell R et al (2007) Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells. J Endocrinol 195:125–131PubMedCrossRefGoogle Scholar
  7. 7.
    Larsson T, Nisbeth U, Ljunggren O et al (2003) 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 64:2272–2279PubMedCrossRefGoogle Scholar
  8. 8.
    Kalantar-Zadeh K, Kuwae N, Regidor DL et al (2006) Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int 70:771–780PubMedCrossRefGoogle Scholar
  9. 9.
    Wolf M, Shah A, Gutierrez O et al (2007) Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int 72:1004–1013PubMedCrossRefGoogle Scholar
  10. 10.
    Taskapan H (2012) Is 24,25(OH)D level really high in dialysis patients with high FGF23 levels? Int Urol Nephrol 44:1135–1144PubMedCrossRefGoogle Scholar
  11. 11.
    Mirza MA, Larsson A, Lind L et al (2009) Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis 205:385–390PubMedCrossRefGoogle Scholar
  12. 12.
    Mirza MA, Hansen T, Johansson L et al (2009) Relationship between circulating FGF23 and total body atherosclerosis in the community. Nephrol Dial Transplant 24:3125–3131PubMedCrossRefGoogle Scholar
  13. 13.
    Mirza MA, Larsson A, Melhus H et al (2009) Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population. Atherosclerosis 207:546–551PubMedCrossRefGoogle Scholar
  14. 14.
    Gutierrez OM, Januzzi JL, Isakova T et al (2009) Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 119:2545–2552PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Gutierrez OM, Mannstadt M, Isakova T et al (2008) Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359:584–592PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Echida Y, Ogawa T, Otauka K et al (2012) Serum non-high-density lipoprotein cholesterol (non-HDL-C) levels and cardiovascular mortality in chronic hemodialysis patients. Clin Exp Nephrol 16:767–772PubMedCrossRefGoogle Scholar
  17. 17.
    Tamei N, Ogawa T, Ishida H et al (2011) Serum fibroblast growth factor-23 levels and progression of aortic arch calcification in non-diabetic patients on chronic hemodialysis. J Atheroscler Thromb 18:217–223PubMedCrossRefGoogle Scholar
  18. 18.
    Kojima F, Uchida K, Ogawa T et al (2008) Plasma levels of fibroblast growth factor-23 and mineral metabolism in diabetic and non-diabetic patients on chronic hemodialysis. Int Urol Nephrol 40:1067–1074PubMedCrossRefGoogle Scholar
  19. 19.
    Daugirdas JT (1993) Second generation logarithmic estimates of single-pool variable volume Kt/V: an analysis of error. J Am Soc Nephrol 4:1205–1213PubMedGoogle Scholar
  20. 20.
    Jean G, Terrat JC, Vanel T et al (2009) High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients. Nephrol Dial Transplant 24:2792–2796PubMedCrossRefGoogle Scholar
  21. 21.
    Olauson H, Qureshi AR, Miyamoto T et al (2010) Relation between serum fibroblast growth factor-23 level and mortality in incident dialysis patients: are gender and cardiovascular disease confounding the relationship? Nephrol Dial Transplant 25:3033–3038PubMedCrossRefGoogle Scholar
  22. 22.
    Onufrak SJ, Bellasi A, Cardarelli F et al (2009) Investigation of gender heterogeneity in the associations of serum phosphorus with incident coronary artery disease and all-cause mortality. Am J Epidemiol 169:67–77PubMedCrossRefGoogle Scholar
  23. 23.
    Hsu HJ, Wu MS (2009) Fibroblast growth factor 23: a possible cause of left ventricular hypertrophy in hemodialysis patients. Am J Med Sci 337:116–122PubMedCrossRefGoogle Scholar
  24. 24.
    Canziani ME, Tomiyama C, Higa A (2011) Fibroblast growth factor 23 in chronic kidney disease: bridging the gap between bone mineral metabolism and left ventricular hypertrophy. Blood Purif 31:26–32PubMedCrossRefGoogle Scholar
  25. 25.
    Kirkpantur A, Balci M, Gurbuz OA et al (2011) Serum fibroblast growth factor-23 (FGF-23) levels are independently associated with left ventricular mass and myocardial performance index in maintenance haemodialysis patients. Nephrol Dial Transplant 26:1346–1354PubMedCrossRefGoogle Scholar
  26. 26.
    Faul C, Amaral AP, Oskouei B et al (2011) FGF23 induces left ventricular hypertrophy. J Clin Invest 121:4393–4408PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Jean G, Bresson E, Terrat JC et al (2009) Peripheral vascular calcification in long-haemodialysis patients: associated factors and survival consequences. Nephrol Dial Transplant 24:948–955PubMedCrossRefGoogle Scholar
  28. 28.
    Nasrallah MM, El-Shehaby AR, Salem MM et al (2010) Fibroblast growth factor-23 (FGF-23) is independently correlated to aortic calcification in haemodialysis patients. Nephrol Dial Transplant 25:2679–2685PubMedCrossRefGoogle Scholar
  29. 29.
    Desiardins L, Liabeuf S, Renard C et al (2012) FGF23 is independently associated with vascular calcification but not bone mineral density in patients at various CKD stages. Osteoporos Int 23:2017–2025CrossRefGoogle Scholar
  30. 30.
    Stenvinkel P, Pecoits-Filho R, Lindholm B (2003) Coronary artery disease in end-stage renal disease: no longer a simple plumbing problem. J Am Soc Nephrol 7:1927–1939CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Himiko Sugimoto
    • 1
  • Tetsuya Ogawa
    • 2
  • Yuko Iwabuchi
    • 1
  • Kuniaki Otsuka
    • 2
  • Kosaku Nitta
    • 1
  1. 1.Department of Medicine, Kidney CenterTokyo Women’s Medical UniversityShinjuku-kuJapan
  2. 2.Department of Medicine, Medical Center EastTokyo Women’s Medical UniversityArakawa-kuJapan

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