Is fetuin-A a biomarker of dialysis access dysfunction?

Background: The arteriovenous (AV) access function of hemodialysis (HD) patients can be impaired by afferent artery stiffness due to preexisting microcalcification and by venous stenosis secondary to neointimal hyperplasia in whose development participates an upregulated local inflammatory process. Fetuin-A is a circulating potent inhibitor of vascular calcification and plays an important anti-inflammatory role. The aims of this prospective study were to investigate the relationship between baseline serum fetuin-A levels and: blood flow (Q(A)) values at baseline, AV access failure (thrombosis or intervention for stenosis) during follow-up and primary unassisted AV access patency. Methods: We measured baseline serum fetuin-A levels and Q(A) values of the AV access in 64 HD patients under routine Q(A) surveillance for stenosis. Patients were classified into tertiles according to their baseline fetuin-A levels (g/L): <0.5 (tertile-1), 0.5-1.20 (tertile-2), and >1.20 (tertile-3). Results: Fetuin-A was positively correlated with Q(A) (Spearman coefficient = 0.311, p = 0.012). Fourteen patients (21.9%) underwent AV access failure and they had lower fetuin-A (0.59 +/- 0.32 g/L) and lower Q(A) (739.4 +/- 438.8 mL/min) values at baseline compared with the remaining patients (1.05 +/- 0.65 g/L and 1273.0 +/- 596.3 mL/min, respectively) (p = 0.027 and p < 0.001, respectively). The AV access failure rate was highest (34.8%) in tertile-1 (lowest fetuin-A level). Unadjusted Cox regression analysis showed a decrease in the risk of AV access patency loss by increasing fetuin-A concentration (hazard ratio 0.395 (95% confidence interval: 1.42-1.69), p = 0.044) but it was not confirmed in the adjusted model, although the hazard ratio was low (0.523). Kaplan-Meier analysis showed that patients in tertile-3 (highest fetuin-A concentration) had the highest primary unassisted AV access patency (lambda(2) = 4.68, p = 0.030, log-rank test). Conclusion: If our results are confirmed in further studies, fetuin-A could be used as a circulating biomarker to identify HD patients at greater risk for AV access dysfunction, who would benefit from much closer dialysis access surveillance.