FGF-23 and vascular dysfunction in patients with stage 3 and 4 chronic kidney disease

作者：Yilmaz Mahmut I^*; Sonmez Alper; Saglam Mutlu; Yaman Halil; Kilic Selim; Demirkaya Erkan; Eyileten Tayfun; Caglar Kayser; Oguz Yusuf; Vural Abdulgaffar; Yenicesu Mujdat; Zoccali Carmine

来源：Kidney International, 2010, 78(7): 679-685.

DOI：10.1038/ki.2010.194

• chronic kidney disease
• endothelium
• nitric oxide

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. Kidney International (2010) 78, 679-685; doi:10.1038/ki.2010.194; published online 7 July 2010

• 出版日期2010-10
• 单位中国人民解放军军事医学科学院