FGF-23 and vascular dysfunction in patients with stage 3 and 4 chronic kidney disease.
Studies in animals show that fibroblast growth factor (FGF)-23 interferes with vascular reactivity induced by the nitric oxide (NO) system. To investigate the relationship between circulating FGF-23 levels and the response of forearm blood flow to ischemia (flow-mediated vasodilatation, FMD) and nitroglycerin, we tested 183 patients with stage 3-4 chronic kidney disease (CKD). None of them had cardiovascular complications or were taking drugs interfering with vascular function. Patients with FGF-23 levels above the median had significantly lower glomerular filtration rate, FMD, and fetuin-A levels (an anti-inflammatory molecule and potent inhibitor of calcification). They also had higher proteinuria and phosphate levels when compared to patients whose FGF-23 levels were below the median. The response to nitroglycerin was not different between the two groups. Multiple regression analysis showed that the relationship between FGF-23 and FMD was only modestly sensitive to adjustment for classical risk factors, biomarkers of bone mineral metabolism, high-sensitivity C-reactive protein, and homeostatic model assessment index. Adjustment for asymmetrical dimethyl arginine (ADMA) weakened the strength of this link; however, it remained highly significant. There was no independent association between FGF-23 and nitroglycerin. Thus, attenuation of FMD by ADMA suggests that this endogenous inhibitor of NO synthase may, in part, mediate the vascular effects of FGF-23 in patients with CKD.
Yilmaz
Mahmut I
MI
Department of Nephrology, Gülhane School of Medicine, Etlik-Ankara, Turkey. mahmutiyilmaz@yahoo.com
Sonmez
Alper
A
Saglam
Mutlu
M
Yaman
Halil
H
Kilic
Selim
S
Demirkaya
Erkan
E
Eyileten
Tayfun
T
Caglar
Kayser
K
Oguz
Yusuf
Y
Vural
Abdulgaffar
A
Yenicesu
Mujdat
M
Zoccali
Carmine
C
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000502:physiology; D002908:Chronic Disease; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000502:physiology*; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007674:Kidney Diseases / Q000503:physiopathology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009569:Nitric Oxide / Q000502:physiology; D012307:Risk Factors; D014664:Vasodilation
C000717427:FGF23 protein, human; D009569:Nitric Oxide; D005346:Fibroblast Growth Factors; C018524:N,N-dimethylarginine; D000089703:Fibroblast Growth Factor-23; D001120:Arginine