Serum Fetuin-A in Chronic Renal Disease Patients: Contribution to Endothelial Dysfunction and Hemostatic alteration

Background/Aim: Fetuin-A is a circulating calcium-regulatory glycoprotein that inhibits vascular calcification. In the present study, serum fetuin-A was studied as a novel risk factor for the development of endothelial dysfunction (ED) and hemostatic alteration in patients with chronic renal disease (CRD). Patients and Methods: 15 CRD patients on conservative treatment, 15 end stage renal disease (ESRD) patients on regular hemodialysis (HD) treatment and 15 healthy volunteers were enrolled in the study. Fetuin-A, thrombomodulin (TM), von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), D-dimer, high sensitivity CRP (hs CRP) and IL-6 were measured by ELISA. Results: There was a significant reduction in Fetuin-A levels in CRD and HD patients compared to controls. A significant decrease was also detected in HD group when compared to CRD group. The inflammatory markers, hs CRP and IL-6, were significantly increased in CRD and HD patients in comparison to controls. The increase was also significant on comparing HD group to CRD group. A strong inverse correlation was found between serum fetuin-A and each of hs CRP and IL-6. In addition, regression analysis revealed that hs CRP is an independent determinant of serum fetuin-A level. The traditional markers of ED, TM and vWF, were significantly increased in CRD and HD patients compared to controls. The increase was also significant when HD patients were compared to CRD patients. The significant inverse correlation between fetuin-A and each of TM and vWF supports the hypothesis that low serum fetuin-A with subsequent vascular calcification could be one of the contributing factors for the development of ED in CKD and HD patients. The fibrinolytic parameters tPA, PAI-1 and D-dimer levels were significantly higher in CRD and HD compared to controls. HD patients had significantly higher values of the previously mentioned parameters in comparison to CRD patients. t-PA, PAI-1 and D-dimer were significantly correlated to fetuin-A in CRD and HD patients. Conclusion: The results of this study demonstrate that in CKD and HD patients inflammatory processes are increased and linked to low fetuin-A and vascular calcification which represents a novel risk factor for the development of ED. The interplay of these phenomena could be responsible for the development and progression of accelerated thrombogenesis that is peculiar to renal patients. [Nadia A. Hussein, Ola M. Mahmoud, Manal Y. Zahran, Manar A. Rafaat. Serum Fetuin-A in Chronic Renal Disease Patients: Contribution to Endothelial Dysfunction and Hemostatic alteration. Journal of American Science 2010;6(12):1098-1105]. (ISSN: 1545-1003). http://www.americanscience.org.