Vascular calcification is the most prominent underlying pathological finding in patients with uraemia, and is a predictor of mortality in this population. Fetuin-A (α₂-Heremans Schmid glycoprotein; AHSG) is an important circulating inhibitor of calcification in vivo, and is downregulated during the acute-phase response. We aimed to investigate the hypothesis that AHSG deficiency is directly related to uraemic vascular calcification.

We did a cross-sectional study in 312 stable patients on haemodialysis to analyse the inter-relation of AHSG and C-reactive protein (CRP) and their predictive effect on all-cause and cardiovascular mortality, over a period of 32 months. Subsequently, we tested the capacity of serum to inhibit Ca×PO₄ precipitation in patients on long-term dialysis (n=17) with apparent soft-tissue calcifications, and in those on short-term dialysis (n=8) without evidence of calcifications and cardiovascular disease.

AHSG concentrations in serum were significantly lower in patients on haemodialysis (mean 0·66 g/L [SD 0·28]) than in healthy controls (0·72 [0·19]). Low concentrations of the glycoprotein were associated with raised amounts of CRP and with enhanced cardiovascular (p=0·031) and all-cause mortality (p=0·0013). Sera from patients on long-term dialysis with low AHSG concentrations showed impaired ex-vivo capacity to inhibit Ca×PO₄ precipitation (mean IC₅₀: 9·0 μL serum [SD 3·1] vs 7·5 [0·8] in short-term patients and 6·4 [2·6] in controls). Reconstitution of sera with purified AHSG returned this impairment to normal.

AHSG deficiency is associated with inflammation and links vascular calcification to mortality in patients on dialysis. Activated acute-phase response and AHSG deficiency might account for accelerated atherosclerosis in uraemia.