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

Kidney Int. 2010 Oct;78(7):679-85. doi: 10.1038/ki.2010.194. Epub 2010 Jul 7.

Abstract

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.

MeSH terms

  • Adult
  • Arginine / analogs & derivatives
  • Arginine / physiology
  • Chronic Disease
  • Female
  • Fibroblast Growth Factors / physiology*
  • Forearm / blood supply
  • Humans
  • Kidney Diseases / physiopathology*
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Nitric Oxide / physiology
  • Risk Factors
  • Vasodilation*

Substances

  • Nitric Oxide
  • Fibroblast Growth Factors
  • N,N-dimethylarginine
  • fibroblast growth factor 23
  • Arginine