Plasma levels of fibroblast growth factor-23 and mineral metabolism in diabetic and non-diabetic patients on chronic hemodialysis.
OBJECTIVE
Fibroblast growth factor (FGF) 23 is a circulating factor that regulates phosphate (P) metabolism. Since higher P levels are associated with vascular calcification, we examined the role of serum FGF-23 levels in P metabolism and vascular calcification in hemodialysis (HD) patients with and without diabetes mellitus (DM).


METHODS
Chronic HD patients with DM (n = 39) and without DM (n = 50) were enrolled. Serum samples were obtained before the start of dialysis sessions, and the FGF-23 levels were determined by enzyme-linked immunosorbent assay. Abdominal computed tomography (CT) scan was performed, and the aortic calcification index (ACI) was determined by one examiner, blinded to the patient characteristics. Measurements of bone mineral density (BMD) were performed at the time of ACI estimation.


RESULTS
Log plasma FGF-23 levels were higher in non-DM (3.74 +/- 0.71 pg/ml) than in DM (3.35 +/- 0.74 pg/ml) patients. The log FGF-23 correlated positively with serum creatinine (r = 0.424, P < 0.0001), albumin (r = 0.225, P = 0.0337), Ca (r = 0.392, P = 0.0001), P (r = 0.735, P < 0.0001), and Ca x P product (r = 0.780, P < 0.0001). There were negative correlations between log FGF-23 and age (r = -0.208, P = 0.0497), glucose (r = -0.231, P = 0.0294), and CRP (r = -0.222, P = 0.0359). Multiple regression analyses were performed to explore the correlations between plasma FGF-23 and other factors associated with vascular calcification in all HD patients. Independent variables were selected based on the results of univariate analyses. The significant factors associated with FGF-23 in HD patients were age, serum levels of creatinine, albumin, glucose, Ca, P, and Ca x P product. Plasma FGF levels did not correlate significantly with either ACI or BMD in these patients.


CONCLUSIONS
Our findings indicate that the plasma FGF-23 level is associated with calcium-phosphate metabolism disorders, but not with aortic calcification, in both non-DM and DM patients on chronic HD. In addition, plasma FGF-23 is associated with serum levels of creatinine and albumin. Therefore, the plasma FGF-23 level may provide a reliable marker for Ca and P imbalance and nutritional status in HD patients.
Kojima
Fumiko
F
Department of Medicine, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
Uchida
Keiko
K
Ogawa
Tetsuya
T
Tanaka
Yoshiko
Y
Nitta
Kosaku
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001018:Aortic Diseases / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D015519:Bone Density; D002114:Calcinosis / Q000097:blood; D002118:Calcium / Q000097:blood; D003404:Creatinine / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000097:blood; D011237:Predictive Value of Tests; D012044:Regression Analysis; D006435:Renal Dialysis; D012709:Serum Albumin / Q000378:metabolism; D018709:Statistics, Nonparametric; D014057:Tomography, X-Ray Computed
D001786:Blood Glucose; C000717427:FGF23 protein, human; D010710:Phosphates; D012709:Serum Albumin; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D003404:Creatinine; D002118:Calcium
Nephrol Dial Transplant. 2000 Jul;15(7):1014-21
10862640
J Bone Miner Metab. 2006;24(6):434-8
17072734
N Engl J Med. 2000 May 18;342(20):1478-83
10816185
J Am Soc Nephrol. 2005 Feb;16(2):489-95
15590763
Nephrol Dial Transplant. 2004 Jun;19(6):1489-96
15102961
Nephron Clin Pract. 2003;94(2):c29-32
12845234
J Clin Endocrinol Metab. 2004 Sep;89(9):4489-92
15356053
Arterioscler Thromb Vasc Biol. 1996 Aug;16(8):978-83
8696962
Diabet Med. 1998 Jul;15(7):539-53
9686693
Hum Mol Genet. 2005 Feb 1;14(3):385-90
15590700
J Am Coll Cardiol. 2002 Feb 20;39(4):695-701
11849871
Kidney Int. 2001 Aug;60(2):472-9
11473629
Osteoporos Int. 2006 Oct;17(10):1506-13
16896512
Calcif Tissue Int. 1999 Aug;65(2):112-6
10430641
Am J Kidney Dis. 2003 Aug;42(2):303-9
12900812
Diabetologia. 2002 Oct;45(10):1446-8
12378387
Int Urol Nephrol. 2007;39(4):1209-16
17899431
Nephrol Dial Transplant. 2005 Oct;20(10):2032-5
16030043
Diabetes Metab. 2008 Feb;34 Suppl 1:S16-20
18358422
Bone. 2004 Nov;35(5):1192-9
15542045
Am J Kidney Dis. 2001 Oct;38(4 Suppl 1):S34-7
11576919
J Biol Chem. 2002 Aug 2;277(31):28265-70
12032146
Nephron Clin Pract. 2008;108(4):c278-83
18434749
J Clin Endocrinol Metab. 2002 Nov;87(11):4957-60
12414858
J Clin Invest. 2004 Feb;113(4):561-8
14966565
J Ren Nutr. 2005 Jan;15(1):178-82
15648030
J Am Soc Nephrol. 2007 Mar;18(3):896-903
17267743
Kidney Int. 2004 May;65(5):1943-6
15086938
Biochem Biophys Res Commun. 2000 Oct 22;277(2):494-8
11032749
Radiat Med. 1990 Sep-Oct;8(5):173-8
2075234
J Am Soc Nephrol. 2004 Jul;15(7):1943-51
15213285
Kidney Int Suppl. 1999 Jul;71:S238-41
10412787
Nephrol Dial Transplant. 2005 Nov;20(11):2472-8
16077143
J Am Soc Nephrol. 2008 Feb;19(2):213-6
18094365
Nephron. 2002 Jul;91(3):456-62
12119477
J Am Soc Nephrol. 2005 Sep;16(9):2565-75
16033853