nach oben

Erschienen in:

01.07.2012 | Original Article

FGF23 is independently associated with vascular calcification but not bone mineral density in patients at various CKD stages

verfasst von: L. Desjardins, S. Liabeuf, C. Renard, A. Lenglet, H.-D. Lemke, G. Choukroun, T. B. Drueke, Z. A. Massy, on behalf of the European Uremic Toxin (EUTox) Work Group

Erschienen in: Osteoporosis International | Ausgabe 7/2012

Einloggen, um Zugang zu erhalten

Abstract

Summary

The hormone fibroblast growth factor 23 (FGF23) is involved in mineral homeostasis but may also have a role in vascular calcification and bone mineralization. In a cohort of 142 patients with CKD stages 2–5D, plasma FGF23 was independently associated with aortic calcification but not with pulse wave velocity or bone mineral density.

Introduction

FGF23 is involved in mineral homeostasis but may also have a role in vascular calcification and bone mineralization. Previous studies related to FGF23 and vascular and bone outcomes have been restricted to dialysis patients. The aim of the present study was to establish whether or not plasma FGF23 is associated with aortic and coronary calcification, arterial stiffness, and bone mineral density in patients with early as well as late stages of CKD.

Methods

In a cohort of 142 patients with CKD stages 2–5D, we made routine biochemistry and intact FGF23 determinations, and assessed aortic and coronary calcification, bone mineral density (BMD), and arterial stiffness by multislice spiral computed tomography and automated pulse wave velocity (PWV).

Results

Plasma intact FGF23 levels were elevated in CKD patients; the elevation preceded that of serum phosphate in early-stage CKD. Patients with elevated FGF23 levels had higher aortic and coronary calcification scores than patients with lower FGF23 levels. Multivariate linear regression analysis indicated that only age (p < 0.001) and FGF23 (p = 0.008) were independently associated with aortic calcification score. Plasma FGF23 was neither associated with PWV nor with BMD.

Conclusion

Our data suggest that plasma FGF23 is an independent biomarker of vascular calcification in patients with various CKD stages including early stages. The association between vascular calcification and FGF23 levels appears to be independent of BMD. It remains to be seen whether this association is independent of bone turnover and bone mass.

Liu S, Guo R, Simpson LG, Xiao ZS, Burnham CE, Quarles LD (2003) Regulation of fibroblastic growth factor 23 expression but not degradation by PHEX. J Biol Chem 278:37419–37426PubMedCrossRef

Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI (1997) Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390:45–51PubMedCrossRef

Shimada T, Hasegawa H, Yamazaki Y, Muto T, Hino R, Takeuchi Y, Fujita T, Nakahara K, Fukumoto S, Yamashita T (2004) FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 19:429–435PubMedCrossRef

Nakanishi S, Kazama JJ, Nii-Kono T, Omori K, Yamashita T, Fukumoto S, Gejyo F, Shigematsu T, Fukagawa M (2005) Serum fibroblast growth factor-23 levels predict the future refractory hyperparathyroidism in dialysis patients. Kidney Int 67:1171–1178PubMedCrossRef

Shimada T, Muto T, Urakawa I, Yoneya T, Yamazaki Y, Okawa K, Takeuchi Y, Fujita T, Fukumoto S, Yamashita T (2002) Mutant FGF-23 responsible for autosomal dominant hypophosphatemic rickets is resistant to proteolytic cleavage and causes hypophosphatemia in vivo. Endocrinology 143:3179–3182PubMedCrossRef

Isakova T, Wahl P, Vargas GS, Gutierrez OM, Scialla J, Xie H, Appleby D, Nessel L, Bellovich K, Chen J, Hamm L, Gadegbeku C, Horwitz E, Townsend RR, Anderson CA, Lash JP, Hsu CY, Leonard MB, Wolf M (2011) Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int 79:1370–1378PubMedCrossRef

Vanholder R, Massy Z, Argiles A, Spasovski G, Verbeke F, Lameire N (2005) Chronic kidney disease as cause of cardiovascular morbidity and mortality. Nephrol Dial Transplant 20:1048–1056PubMedCrossRef

Foley RN, Parfrey PS, Sarnak MJ (1998) Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 32:S112–S119PubMedCrossRef

Taal MW, Roe S, Masud T, Green D, Porter C, Cassidy MJ (2003) Total hip bone mass predicts survival in chronic hemodialysis patients. Kidney Int 63:1116–1120PubMedCrossRef

10.

Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Juppner H, Wolf M (2008) Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359:584–592PubMedCrossRef

11.

Blacher J, Guerin AP, Pannier B, Marchais SJ, Safar ME, London GM (1999) Impact of aortic stiffness on survival in end-stage renal disease. Circulation 99:2434–2439PubMed

12.

Jean G, Terrat JC, Vanel T, Hurot JM, Lorriaux C, Mayor B, Chazot C (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

13.

Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, Wahl P, Gutierrez OM, Steigerwalt S, He J, Schwartz S, Lo J, Ojo A, Sondheimer J, Hsu CY, Lash J, Leonard M, Kusek JW, Feldman HI, Wolf M (2011) Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA 305:2432–2439PubMedCrossRef

14.

Nasrallah MM, El-Shehaby AR, Salem MM, Osman NA, El Sheikh E, Sharaf El Din UA (2010) Fibroblast growth factor-23 (FGF-23) is independently correlated to aortic calcification in haemodialysis patients. Nephrol Dial Transplant 25:2679–2685PubMedCrossRef

15.

Jean G, Bresson E, Terrat JC, Vanel T, Hurot JM, Lorriaux C, Mayor B, Chazot C (2009) Peripheral vascular calcification in long-haemodialysis patients: associated factors and survival consequences. Nephrol Dial Transplant 24:948–955PubMedCrossRef

16.

Temmar M, Liabeuf S, Renard C, Czernichow S, Esper NE, Shahapuni I, Presne C, Makdassi R, Andrejak M, Tribouilloy C, Galan P, Safar ME, Choukroun G, Massy Z (2010) Pulse wave velocity and vascular calcification at different stages of chronic kidney disease. J Hypertens 28:163–169PubMedCrossRef

17.

Nakano T, Ninomiya T, Sumiyoshi S, Fujii H, Doi Y, Hirakata H, Tsuruya K, Iida M, Kiyohara Y, Sueishi K (2010) Association of kidney function with coronary atherosclerosis and calcification in autopsy samples from Japanese elders: the Hisayama study. Am J Kidney Dis 55:21–30PubMedCrossRef

18.

Urena P, Bernard-Poenaru O, Ostertag A, Baudoin C, Cohen-Solal M, Cantor T, de Vernejoul MC (2003) Bone mineral density, biochemical markers and skeletal fractures in haemodialysis patients. Nephrol Dial Transplant 18:2325–2331PubMedCrossRef

19.

Manghat P, Fraser WD, Wierzbicki AS, Fogelman I, Goldsmith DJ, Hampson G (2010) Fibroblast growth factor-23 is associated with C-reactive protein, serum phosphate and bone mineral density in chronic kidney disease. Osteoporos Int 21:1853–1861PubMedCrossRef

20.

Mirza MA, Larsson A, Lind L, Larsson TE (2009) Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis 205:385–390PubMedCrossRef

21.

Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41PubMedCrossRef

22.

Fassbender WJ, Brandenburg V, Schmitz S, Sandig D, Simon SA, Windolf J, Stumpf UC (2009) Evaluation of human fibroblast growth factor 23 (FGF-23) C-terminal and intact enzyme-linked immunosorbent-assays in end-stage renal disease patients. Clin Lab 55:144–152PubMed

23.

Stevens LA, Coresh J, Schmid CH, Feldman HI, Froissart M, Kusek J, Rossert J, Van Lente F, Bruce RD 3rd, Zhang YL, Greene T, Levey AS (2008) Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis 51:395–406PubMedCrossRef

24.

National Kidney Foundation (2002) K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39:S1–S266CrossRef

25.

Agatston AS, Janowitz WR, Hildner FJ, Zusmer NR, Viamonte M Jr, Detrano R (1990) Quantification of coronary artery calcium using ultrafast computed tomography. J Am Coll Cardiol 15:827–832PubMedCrossRef

26.

Raggi P, James G, Burke SK, Bommer J, Chasan-Taber S, Holzer H, Braun J, Chertow GM (2005) Decrease in thoracic vertebral bone attenuation with calcium-based phosphate binders in hemodialysis. J Bone Miner Res 20:764–772PubMedCrossRef

27.

Zureik M, Temmar M, Adamopoulos C, Bureau JM, Courbon D, Thomas F, Bean K, Touboul PJ, Ducimetiere P, Benetos A (2002) Carotid plaques, but not common carotid intima-media thickness, are independently associated with aortic stiffness. J Hypertens 20:85–93PubMedCrossRef

28.

Asmar R, Benetos A, Topouchian J, Laurent P, Pannier B, Brisac AM, Target R, Levy BI (1995) Assessment of arterial distensibility by automatic pulse wave velocity measurement. Validation and clinical application studies. Hypertension 26:485–490PubMed

29.

Barreto DV, Barreto FC, Liabeuf S, Temmar M, Boitte F, Choukroun G, Fournier A, Massy ZA (2009) Vitamin D affects survival independently of vascular calcification in chronic kidney disease. Clin J Am Soc Nephrol 4:1128–1135PubMedCrossRef

30.

Gutierrez OM, Januzzi JL, Isakova T, Laliberte K, Smith K, Collerone G, Sarwar A, Hoffmann U, Coglianese E, Christenson R, Wang TJ, deFilippi C, Wolf M (2009) Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation 119:2545–2552PubMedCrossRef

31.

Stubbs JR, Liu S, Tang W, Zhou J, Wang Y, Yao X, Quarles LD (2007) Role of hyperphosphatemia and 1,25-dihydroxyvitamin D in vascular calcification and mortality in fibroblastic growth factor 23 null mice. J Am Soc Nephrol 18:2116–2124PubMedCrossRef

32.

Razzaque MS, Sitara D, Taguchi T, St-Arnaud R, Lanske B (2006) Premature aging-like phenotype in fibroblast growth factor 23 null mice is a vitamin D-mediated process. FASEB J 20:720–722PubMed

33.

Shimada T, Mizutani S, Muto T, Yoneya T, Hino R, Takeda S, Takeuchi Y, Fujita T, Fukumoto S, Yamashita T (2001) Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia. Proc Natl Acad Sci USA 98:6500–6505PubMedCrossRef

34.

Ichikawa S, Imel EA, Kreiter ML, Yu X, Mackenzie DS, Sorenson AH, Goetz R, Mohammadi M, White KE, Econs MJ (2007) A homozygous missense mutation in human KLOTHO causes severe tumoral calcinosis. J Clin Invest 117:2684–2691PubMedCrossRef

35.

Hu MC, Shi M, Zhang J, Quinones H, Griffith C, Kuro-o M, Moe OW (2010) Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol 22:124–136PubMedCrossRef

36.

Manghat P, Souleimanova I, Cheung J, Wierzbicki AS, Harrington DJ, Shearer MJ, Chowienczyk P, Fogelman I, Goldsmith D, Hampson G (2011) Association of bone turnover markers and arterial stiffness in pre-dialysis chronic kidney disease (CKD). Bone 48:1127–1132PubMedCrossRef

37.

Raggi P, Bellasi A, Ferramosca E, Block GA, Muntner P (2007) Pulse wave velocity is inversely related to vertebral bone density in hemodialysis patients. Hypertension 49:1278–1284PubMedCrossRef

38.

Toussaint ND, Lau KK, Strauss BJ, Polkinghorne KR, Kerr PG (2008) Associations between vascular calcification, arterial stiffness and bone mineral density in chronic kidney disease. Nephrol Dial Transplant 23:586–593PubMedCrossRef

39.

Sitara D, Kim S, Razzaque MS, Bergwitz C, Taguchi T, Schuler C, Erben RG, Lanske B (2008) Genetic evidence of serum phosphate-independent functions of FGF-23 on bone. PLoS Genet 4:e1000154PubMedCrossRef

40.

Wesseling-Perry K, Pereira RC, Wang H, Elashoff RM, Sahney S, Gales B, Juppner H, Salusky IB (2009) Relationship between plasma fibroblast growth factor-23 concentration and bone mineralization in children with renal failure on peritoneal dialysis. J Clin Endocrinol Metab 94:511–517PubMedCrossRef

41.

Oliveira RB, Cancela AL, Graciolli FG, Dos Reis LM, Draibe SA, Cuppari L, Carvalho AB, Jorgetti V, Canziani ME, Moyses RM (2010) Early control of PTH and FGF23 in normophosphatemic CKD patients: a new target in CKD-MBD therapy? Clin J Am Soc Nephrol 5:286–291PubMedCrossRef

Titel: FGF23 is independently associated with vascular calcification but not bone mineral density in patients at various CKD stages
verfasst von: L. Desjardins
S. Liabeuf
C. Renard
A. Lenglet
H.-D. Lemke
G. Choukroun
T. B. Drueke
Z. A. Massy
on behalf of the European Uremic Toxin (EUTox) Work Group
Publikationsdatum: 01.07.2012
Verlag: Springer-Verlag
Erschienen in: Osteoporosis International / Ausgabe 7/2012
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-011-1838-0

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen.
» Jetzt entdecken

Neu im Fachgebiet Orthopädie und Unfallchirurgie

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Arthroskopie kann Knieprothese nicht hinauszögern

25.04.2024 Gonarthrose Nachrichten

Ein arthroskopischer Eingriff bei Kniearthrose macht im Hinblick darauf, ob und wann ein Gelenkersatz fällig wird, offenbar keinen Unterschied.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Ärztliche Empathie hilft gegen Rückenschmerzen

23.04.2024 Leitsymptom Rückenschmerzen Nachrichten

Personen mit chronischen Rückenschmerzen, die von einfühlsamen Ärzten und Ärztinnen betreut werden, berichten über weniger Beschwerden und eine bessere Lebensqualität.

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Summary

Introduction

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 7/2012

Frailty and sarcopenia: definitions and outcome parameters

Vertebral body bone strength: the contribution of individual trabecular element morphology

A clinical decision rule to enhance targeted bone mineral density testing in healthy mid-life women

A follow-up association study of two genetic variants for bone mineral density variation in Caucasians

Anatomical distribution of vertebral fractures: comparison of pediatric and adult spines