Serum fetuin‐A concentration and fetuin‐A‐containing calciprotein particles in patients with chronic inflammatory disease and renal failure

Abstract

Fetuin-A (Fet-A) is an important regulator of extracellular matrix mineralization. Fet-A plays a critical role in the formation and stabilization of high molecular weight colloidal protein-mineral complexes known as calciprotein particles (CPP). The aim of this study was to examine the effects of inflammation, renal function and dialysis modality on serum Fet-A and CPP. This is an observational study of patients with chronic kidney disease (CKD) and those with chronic inflammatory disease (CID) but normal renal function. Serum CPP were quantified indirectly by analysing the apparent reduction in serum Fet-A concentration (reduction ratio, RR) after high-speed centrifugation. Serum total Fet-A concentrations are reduced in renal disease and in patients with CID. CPP were not detectable in the serum of normal individuals. CPP represent an increasing percentage of total circulating Fet-A concentrations in patients with CID (RR, 13.3 ± 8.5%), as well as in patients with pre-dialysis CKD (12.4 ± 7.3%) and those undergoing peritoneal dialysis (RR, 22.8 ± 6.0%) or haemodialysis (RR, 38.1 ± 12.8%). The highest Fet-A RR were found in patients with calcific uraemic arteriolopathy (CUA) on haemodialysis (73.9 ± 15.6%). Serum total Fet-A concentrations and Fet-A reduction ratios decreased during a single haemodialysis session, by 24% (P < 0.001) and 34% (P < 0.001), respectively. Inflammation appears to be associated with mineral stress even in the absence of renal dysfunction. Patients with CUA on haemodialysis have very high serum Fet-A reduction ratios, suggesting that this measurement may have a prognostic/diagnostic role in this condition.