Relationship of fetuin-A with glomerular filtration rate and endothelial dysfunction in moderate-severe chronic kidney disease

Background: In end-stage renal disease, fetuin-A has been demonstrated to be reduced and inversely related to cardiovascular mortality. This study had 2 distinct aims. The first was to verify if circulating concentration of fetuin-A may depend on renal function in patients with chronic kidney disease (CKD). Furthermore, we analyzed the correlation of fetuin-A with the biomarker of endothelial dysfunction endothelin-1 (ET-1), and with the inflammatory cytokine interleukin-6 (IL-6). Methods: In 108 subjects with stage 3-5 CKD, plasma levels of fetuin-A, ET-1 and IL-6 were assayed. Patients were studied first as a whole group and then were divided according to stages of CKD and fetuin-A tertiles. Results: Fetuin-A concentration decreased in parallel with the increase in ET-1 and IL-6 levels as renal function declined. Multiple regression analysis showed that fetuin-A was independently associated with estimated glomerular filtration rate (beta=0.386; p<0.001), IL-6 (beta=-0.393; p=0.001) and ET-1 (beta=-0.219; p=0.02), in a multivariate model including also sex, parathyroid hormone and the calcium x phosphorus product. Conclusions: These results seem to indicate that in CKD, even when not severe, inflammatory processes are increased and linked to endothelial dysfunction, worsening progressively with the decline of renal function.