Skip to main content
Top
Published in: International Urology and Nephrology 1/2014

01-01-2014 | Nephrology - Original Paper

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

Authors: Himiko Sugimoto, Tetsuya Ogawa, Yuko Iwabuchi, Kuniaki Otsuka, Kosaku Nitta

Published in: International Urology and Nephrology | Issue 1/2014

Login to get access

Abstract

Background

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.

Methods

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.

Results

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).

Conclusion

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.
Literature
1.
go back to reference 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 277:494–498PubMedCrossRef 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 277:494–498PubMedCrossRef
2.
go back to reference 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 69:1945–1953PubMedCrossRef 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 69:1945–1953PubMedCrossRef
3.
go back to reference 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 14:239–243PubMedCrossRef 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 14:239–243PubMedCrossRef
4.
go back to reference 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 277:28265–28270PubMedCrossRef 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 277:28265–28270PubMedCrossRef
5.
go back to reference 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 314:409–414PubMedCrossRef 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 314:409–414PubMedCrossRef
6.
go back to reference 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 195:125–131PubMedCrossRef 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 195:125–131PubMedCrossRef
7.
go back to reference 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 64:2272–2279PubMedCrossRef 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 64:2272–2279PubMedCrossRef
8.
go back to reference 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 70:771–780PubMedCrossRef 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 70:771–780PubMedCrossRef
9.
go back to reference Wolf M, Shah A, Gutierrez O et al (2007) Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int 72:1004–1013PubMedCrossRef Wolf M, Shah A, Gutierrez O et al (2007) Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int 72:1004–1013PubMedCrossRef
10.
go back to reference Taskapan H (2012) Is 24,25(OH)D level really high in dialysis patients with high FGF23 levels? Int Urol Nephrol 44:1135–1144PubMedCrossRef Taskapan H (2012) Is 24,25(OH)D level really high in dialysis patients with high FGF23 levels? Int Urol Nephrol 44:1135–1144PubMedCrossRef
11.
go back to reference Mirza MA, Larsson A, Lind L et al (2009) Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis 205:385–390PubMedCrossRef Mirza MA, Larsson A, Lind L et al (2009) Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis 205:385–390PubMedCrossRef
12.
go back to reference Mirza MA, Hansen T, Johansson L et al (2009) Relationship between circulating FGF23 and total body atherosclerosis in the community. Nephrol Dial Transplant 24:3125–3131PubMedCrossRef Mirza MA, Hansen T, Johansson L et al (2009) Relationship between circulating FGF23 and total body atherosclerosis in the community. Nephrol Dial Transplant 24:3125–3131PubMedCrossRef
13.
go back to reference 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 207:546–551PubMedCrossRef 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 207:546–551PubMedCrossRef
14.
go back to reference Gutierrez OM, Januzzi JL, Isakova T et al (2009) Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 119:2545–2552PubMedCentralPubMedCrossRef Gutierrez OM, Januzzi JL, Isakova T et al (2009) Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 119:2545–2552PubMedCentralPubMedCrossRef
15.
go back to reference Gutierrez OM, Mannstadt M, Isakova T et al (2008) Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359:584–592PubMedCentralPubMedCrossRef Gutierrez OM, Mannstadt M, Isakova T et al (2008) Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359:584–592PubMedCentralPubMedCrossRef
16.
go back to reference 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 16:767–772PubMedCrossRef 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 16:767–772PubMedCrossRef
17.
go back to reference 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 18:217–223PubMedCrossRef 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 18:217–223PubMedCrossRef
18.
go back to reference 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 40:1067–1074PubMedCrossRef 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 40:1067–1074PubMedCrossRef
19.
go back to reference Daugirdas JT (1993) Second generation logarithmic estimates of single-pool variable volume Kt/V: an analysis of error. J Am Soc Nephrol 4:1205–1213PubMed Daugirdas JT (1993) Second generation logarithmic estimates of single-pool variable volume Kt/V: an analysis of error. J Am Soc Nephrol 4:1205–1213PubMed
20.
go back to reference 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 24:2792–2796PubMedCrossRef 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 24:2792–2796PubMedCrossRef
21.
go back to reference 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 25:3033–3038PubMedCrossRef 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 25:3033–3038PubMedCrossRef
22.
go back to reference 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 169:67–77PubMedCrossRef 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 169:67–77PubMedCrossRef
23.
go back to reference Hsu HJ, Wu MS (2009) Fibroblast growth factor 23: a possible cause of left ventricular hypertrophy in hemodialysis patients. Am J Med Sci 337:116–122PubMedCrossRef Hsu HJ, Wu MS (2009) Fibroblast growth factor 23: a possible cause of left ventricular hypertrophy in hemodialysis patients. Am J Med Sci 337:116–122PubMedCrossRef
24.
go back to reference 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 31:26–32PubMedCrossRef 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 31:26–32PubMedCrossRef
25.
go back to reference 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 26:1346–1354PubMedCrossRef 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 26:1346–1354PubMedCrossRef
27.
go back to reference Jean G, Bresson E, Terrat JC et al (2009) Peripheral vascular calcification in long-haemodialysis patients: associated factors and survival consequences. Nephrol Dial Transplant 24:948–955PubMedCrossRef Jean G, Bresson E, Terrat JC et al (2009) Peripheral vascular calcification in long-haemodialysis patients: associated factors and survival consequences. Nephrol Dial Transplant 24:948–955PubMedCrossRef
28.
go back to reference 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 25:2679–2685PubMedCrossRef 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 25:2679–2685PubMedCrossRef
29.
go back to reference 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 23:2017–2025CrossRef 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 23:2017–2025CrossRef
30.
go back to reference 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 7:1927–1939CrossRef 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 7:1927–1939CrossRef
Metadata
Title
Relationship between serum fibroblast growth factor-23 level and mortality in chronic hemodialysis patients
Authors
Himiko Sugimoto
Tetsuya Ogawa
Yuko Iwabuchi
Kuniaki Otsuka
Kosaku Nitta
Publication date
01-01-2014
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 1/2014
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-013-0386-2

Other articles of this Issue 1/2014

International Urology and Nephrology 1/2014 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.