Fully phosphorylated fetuin-A forms a mineral complex in the serum of rats with adenine-induced renal failure.
The serum glycoprotein fetuin-A is an important inhibitor of extra-osseous calcification, but correlations between serum fetuin-A levels and the extent of vascular calcification are controversial. In this study, we used a rat model of adenine-induced renal failure with secondary hyperparathyroidism that exhibits all characteristic features of patients with chronic kidney disease. These rats had medial vascular calcification along with reduced levels of both serum and hepatic fetuin-A. Treatment with an inhibitor of ectopic calcification, alendronate, decreased bone turnover and eliminated completely the vascular calcification in this rat model, but there was no change in the levels of hepatic and serum fetuin-A. Centrifugation of the serum of untreated rats with renal failure gave a small precipitate composed of fetuin-A, calcium, magnesium, and phosphate; this complex, absent from normal rat serum, was not found in the serum of alendronate-treated rats with renal failure. Rat serum contained three types of phosphorylated fetuin-A, as well as unphosphorylated forms, but only the fully phosphorylated fetuin-A was present in the mineral complex. The amount of this complex reflected the risk of mineral precipitation. Our results suggest that the measurement of serum fetuin-mineral complex rather than fetuin-A alone might provide a better indication of extra-osseous calcification propensity.
Matsui
Isao
I
Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
Hamano
Takayuki
T
Mikami
Satoshi
S
Fujii
Naohiko
N
Takabatake
Yoshitsugu
Y
Nagasawa
Yasuyuki
Y
Kawada
Noritaka
N
Ito
Takahito
T
Rakugi
Hiromi
H
Imai
Enyu
E
Isaka
Yoshitaka
Y
D000225:Adenine / Q000009:adverse effects; D019386:Alendronate / Q000494:pharmacology; D000818:Animals; D002114:Calcinosis / Q000188:drug therapy / Q000209:etiology*; D011232:Chemical Precipitation; D008099:Liver / Q000378:metabolism; D008297:Male; D008903:Minerals / Q000097:blood / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000097:blood* / Q000139:chemically induced / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism*
D008903:Minerals; D000509:alpha-Fetoproteins; D000225:Adenine; D019386:Alendronate