FGF23 is independently associated with vascular calcification but not bone mineral density in patients at various CKD stages
- 981 Downloads
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.
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.
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).
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.
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.
KeywordsBone mineral density Chronic kidney disease CKD stage FGF23 Pulse wave velocity Vascular calcification
Conflicts of interest
- 2.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 390:45–51PubMedCrossRefGoogle Scholar
- 5.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 143:3179–3182PubMedCrossRefGoogle Scholar
- 6.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 79:1370–1378PubMedCrossRefGoogle Scholar
- 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 305:2432–2439PubMedCrossRefGoogle Scholar
- 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 28:163–169PubMedCrossRefGoogle Scholar
- 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 55:21–30PubMedCrossRefGoogle Scholar
- 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 51:395–406PubMedCrossRefGoogle Scholar
- 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 119:2545–2552PubMedCrossRefGoogle Scholar
- 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 94:511–517PubMedCrossRefGoogle Scholar