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Ketteler, M. et al.

Ketteler, Bongartz, Westenfeld, Wildberger, Mahnken, Böhm, Metzger, Wanner, Jahnen-Dechent, Floege,

Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study.

BACKGROUND: Vascular calcification is the most prominent underlying pathological finding in patients with uraemia, and is a predictor of mortality in this population. Fetuin-A (alpha2-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. METHODS: 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 CaxPO4 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. FINDINGS: 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 CaxPO4 precipitation (mean IC50: 9.0 microL 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.Interpretation 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.[1]

References

Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study. Ketteler, M., Bongartz, P., Westenfeld, R., Wildberger, J.E., Mahnken, A.H., Böhm, R., Metzger, T., Wanner, C., Jahnen-Dechent, W., Floege, J. Lancet (2003) [Pubmed]

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