Fibroblast growth factor 23 and matrix-metalloproteinases in patients with chronic kidney disease: are they associated with cardiovascular disease?

Kidney Blood Press Res. 2009;32(4):276-83. doi: 10.1159/000243050. Epub 2009 Oct 1.

Abstract

Background: High cardiovascular risk in patients with chronic kidney disease (CKD) may be related to mineral disorder and microinflammation. Fibroblast growth factor 23 (FGF-23) is a phosphatonin and inhibitor of calcitriol synthesis, which is associated with poor prognosis in CKD patients starting dialysis. Matrix-metalloproteinases (MMP-2, MMP-9) contribute to myocardial remodeling and arterial calcification. FGF-23 and MMPs levels are altered in CKD, however, little is known about their association and relation to cardiovascular (CV) disease.

Methods: Standard laboratory parameters, plasma levels of MMP-2, MMP-9, FGF-23, PAPP-A and CV disease history were assessed in 80 patients with CKD 1-5 and 44 healthy control subjects.

Results: FGF-23 and MMP-2 (assessed by ELISA) were higher in CKD patients compared to controls. FGF-23 increased from CKD 3, whereas MMP-2 increased only in CKD 5. FGF-23 was positively associated with MMP-2, adjusted to age, eGFR, phosphatemia, calcitriol and parathormone. FGF-23 independently correlated with parathormone and inversely with calcitriol, whereas MMP-2 was related to phosphatemia. FGF-23 was higher in subjects with a history of CV disease compared to those free of such history (559.0 vs.184.0 RU/ml), adjusted to age and eGFR.

Conclusion: Our data suggest a possible relationship between FGF-23, MMP-2 and CV disease in CKD. Potential causality of this association remains to be elucidated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / physiology
  • Biomarkers
  • Calcitriol / blood
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / metabolism*
  • Cytokines / blood
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / metabolism*
  • Humans
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / metabolism*
  • Kidney Function Tests
  • Lipids / blood
  • Male
  • Matrix Metalloproteinases / metabolism*
  • Middle Aged
  • Parathyroid Hormone / blood
  • Serum Albumin / metabolism
  • Sex Characteristics
  • Vitamin D / therapeutic use
  • Vitamins / therapeutic use

Substances

  • Biomarkers
  • Cytokines
  • FGF23 protein, human
  • Lipids
  • Parathyroid Hormone
  • Serum Albumin
  • Vitamins
  • Vitamin D
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Matrix Metalloproteinases
  • Calcitriol