Fetuin-Mineral Complex Reflects Extraosseous Calcification Stress in CKD

Fetuin A is an important inhibitor of extraosseous calcification, but some of the studies that used ELISAs did not identify a significant relationship between serum fetuin A levels and vascular calcification in patients with chronic kidney disease (CKD) Here, we used centrifugation to separate a fetuin-mineral complex (FMC) composed of fetuin-A fibrinogen fibronectin 1 and calcium from the serum of hemodialysis patients In addition we analyzed serum fetuin A levels of 73 patients with diabetes and CKD (predialysis) after centrifugation Fetuin-A concentrations were significantly lower in supernatants than in serum from patients at any stage of CKD indicating systemic circulation of FMC in these patients With greater severity of CKD the contribution of FMC to total fetuin A increased Despite the absence of a correlation between serum fetuin A and coronary artery calcification scores (CACS), supernatant fetuin-A negatively correlated with CACS and the extent to which centrifugation reduced fetuin A (reduction ratio [RR]) positively correlated with CACS In a longitudinal study of 12 hemodialysis patients with secondary hyperparathyroidism, parathyroidectomy and cinacalcet therapy each significantly reduced the RR without changing supernatant fetuin-A levels after 1 month, suggesting a reduction in FMC Moreover, the magnitude of cinacalcet-induced reduction in parathyroid hormone correlated with the decrease in RR but not with changes in serum or supernatant fetuin A These data suggest that a quantitative measure of FMC, not supernatant or serum fetuin A as measured in previous studies, reflects extraosseous calcification stress