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


CONCLUSIONS
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.
Department of Nephrology, First Faculty of Medicine, Charles University, Hradec Králové, Czech Republic. mpeiskerova @ seznam.cz
M
M
Peiskerová
M
M
Kalousová
M
M
Kratochvílová
S
S
Dusilová-Sulková
J
J
Uhrová
S
S
Bandúr
I M
IM
Malbohan
T
T
Zima
V
V
Tesar
D000368:Aged; D000375:Aging / Q000502:physiology; D015415:Biomarkers; D002117:Calcitriol / Q000097:blood; D002318:Cardiovascular Diseases / Q000150:complications / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism*; D007677:Kidney Function Tests; D008055:Lipids / Q000097:blood; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D012709:Serum Albumin / Q000378:metabolism; D012727:Sex Characteristics; D014807:Vitamin D / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use
D015415:Biomarkers; D016207:Cytokines; C000717427:FGF23 protein, human; D008055:Lipids; D010281:Parathyroid Hormone; D012709:Serum Albumin; D014815:Vitamins; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D020782:Matrix Metalloproteinases; D002117:Calcitriol