Visfatin and Fetuin-A: Novel Markers for Endothelial Dysfunction in Chronic Kidney Disease

Background: Endothelial dysfunction (ED) has a major role in the cardiovascular outcome of patients with chronic kidney disease (CKD). The hallmark of endothelial dysfunction is impaired nitric oxide-mediated endothelial-dependent vasodilatation. Visfatin is an adipocytokine that has recently generated much interest and could contribute to endothelial dysfunction. Fetuin-A may be one of the contributing factors for the development of ED in CKD patients. In addition, fetuin-A 256Ser/Ser (allele G) might affect serum fetuin-A levels. The aim of the present work is to study the role of visfatin and fetuin-A in patients with different stages of CKD in correlation with the level of NO (nitrite /nitrate) as a settled marker of endothelial dysfunction. Also, to study the relation between fetuin-A gene polymorphisms and the susceptibility to ED in patients with CKD in different stages; and identifying the effect of fetuin-A gene polymorphisms on the level of serum fetuin-A in CKD patients. Methods: the present study included sixty patients at different stages of CKD with age range from 18 to 60 years old. All patients were non-diabetic and arranged in five groups according to the stage of CKD assessed GFR from stage 1 to 5 representing the groups from I to V. Serum visfatin and serum fetuin-A were measured using ELISA technique and serum NO was measured as (total nitrate and nitrite) using the Griess reaction. Serum levels of glucose, triglycerides, total cholesterol and HDL-cholesterol were estimated by enzymatic colorimetric methods. LDL-cholesterol was then calculated using Friedewald's formula. Genotyping for the common functional polymorphisms on fetuin-A (Thr256Ser) using polymerase chain reaction (PCR) technique was performed. Results: A statistically significant elevation of serum total nitrate and nitrite and serum visfatin in CKD patients compared to controls respectively, while serum fetuin-A showed statistically significant decrease in CKD patients compared to the control group. Serum total nitrate and nitrite levels were significantly increased in all stages of CKD, while serum visfatin was significantly increased in stages 2 to 5 of CKD. Serum fetuin-A showed significant decrease in stages 2 to 5 of CKD. There was no statistically significant difference between the studied CKD cases and the control group as regards to the frequencies of the three genotypes of fetuin-A (C. G); Thr256Ser polymorphism. In both CKD patients and the control group, the distribution of the fetuin-A (C. G); Thr256Ser gene polymorphisms did not show significant correlation with low serum fetuin-A levels. A significant positive correlation was found between serum levels of total nitrate and nitrite and serum levels of (visfatin, triglycerides, total cholesterol, LDL-cholesterol), while A significant negative correlation was found between serum levels of total nitrate and nitrite and serum levels of (fetuin-A and HDL-cholesterol) in CKD patients. Stepwise regression analysis revealed that the strongest predictors of endothelial dysfunction were found to be serum visfatin and HDL-cholesterol as they could explain significantly 52% of the changes in total nitrate and nitrite. Conclusion: The results of the present study suggest that high serum levels of visfatin and total nitrate and nitrite in CKD patients may contribute to impaired endothelial functions in CKD. Visfatin and fetuin-A may be novel markers for endothelial dysfunction in CKD patients and in diagnosis of early stages of CKD and they may play a role in uremia-related atherosclerosis. The distribution of the fetuin-A (C. G); Thr256Ser gene polymorphisms may does not affect serum fetuin-A levels.[Mohamed A. Zeidan, Gihan M. Sharara, Howaida S. Suliman, Montasser M. Zeid, Sameh S. Zytoun, Hanan M. Nomeir. Visfatin and Fetuin-A: Novel Markers for Endothelial Dysfunction in Chronic Kidney Disease. Life Sci J 2012;9(2):227-243]. (ISSN:1097-8135). http://www.lifesciencesite.com.38