Fetuin-A in kidney disease

Fetuin-A is a hepatic-origin protein that secreted into the circulation (۱). Fetuins had relationships with a cluster of proteins that developed from the protein cystatin through gene duplication and interchange of gene segments (۲,۳). Fetuin-A is a ۶۴-kDa glycoprotein which is secreted from both adipose and hepatic tissues (۴). Fetuin-A, interferes with calcification of vessels and regulation of bone metabolism in chronic kidney disease. Additionally, impaired insulin sensitivity and glucose tolerance which are features of insulin resistance have been implicated as a role of this substance. On the other hand, fetuin A significantly facilitates the integration of exogenous fatty acids into cellular triglycerides (۵). Therefore, fetuin A might share a function with fatty acid binding proteins, a family of ۱۴-kDa to ۱۵-kDa proteins. Fetuin-A has been detected as a biomarker for neurodegenerative disease too (۶). Numerous studies had detected that fetuin A inhibits ectopic calcification of the vessels (۷-۹). In fact, fetuin A, is exceedingly responsible for vascular calcification in overweight/obese individuals with chronic renal failure. Additionally, circulating fetuin-A is raised in obesity and the related disorders like type ۲ diabetes mellitus and also metabolic syndrome (۱۰). Elevated fetuin-A level may be related to the development of insulin resistance in diabetes and chronic renal failure and diabetic kidney disease too. Besides, serum levels of fetuin-A have been detected to have a positive association with macrovascular disease of high-risk type ۲ diabetes, while no association with microvascular complications was found (۱۱). More recently it was detected that serum fetuin-A is lower in microalbuminuric diabetic patients compared with normo-albuminuric or macroalbuminuric patients. In addition, lower serum levels of fetuin-A are linked with peripheral arterial disease in individuals with type ۲ diabetes. Likewise, serum fetuin-A values are negatively correlated with atherosclerotic calcified plaques (۱۲).However, the action of insulin on perivascular fat cells and its impact on vascular wall cells are not fully detected (۱۳). The impact of diabetic kidney disease to increase the incidence of chronic renal failure and end-stage renal disease is enormous. Likewise, a correlation of vascular calcification and endothelial dysfunction in various vascular disease have been implicated. In addition, low serum fetuin-A level may be one of the relating factors for the progress of endothelial dysfunction in chronic renal failure individuals (۱۴). Importantly, fetuin-A was newly detected to inhibit ectopic calcification. According to this finding, fetuin-A deficiency was detected to be accompanying with calcification of vessels and increased mortality in hemodialysis patients (۱۵). However, fetuin-A may have other functions. Recently to find the association of fetuin-A with mortality and increased risk estimate in non-dialysis chronic renal failure patients with stages of three to five, Alderson et al, conducted a study on ۴۶۳ patients who recruited to the chronic renal failure standards implementation study (۱۶).

کلیدواژه ها:

Fetuin-A ، Type ۲ diabetes mellitus ، End-stage renal disease ، Hemodialysis