title: Is fetuin-A/alpha2-Heremans-Schmid glycoprotein associated with the metabolic syndrome in patients with chronic kidney disease?
abstract: BACKGROUND
  Components of the metabolic syndrome are highly prevalent in chronic kidney disease (CKD) patients--some of which paradoxically appear to predict an improved outcome in this population. We hypothesized that the circulating calcification inhibitor fetuin-A/AHSG, which is also a natural inhibitor of the tyrosine kinase insulin receptor, could be one factor explaining the association between increased fat mass and a survival advantage in CKD and thus conducted an explorational study to provide preliminary data to support further research into this hypothesis.
  
  
  METHODS
  In a cross-sectional study, we evaluated 198 CKD stage 5 patients (GFR 6.8 +/- 0.2 ml/min; 62% males, mean age 52 +/- 1 years) close to the start of renal replacement therapy. We studied circulating AHSG (ELISA) and two common functional AHSG gene polymorphisms (at amino acids Thr248Met (C-T) and Thr256Ser (C-G) using Pyrosequencing) and related these to multiple components of the metabolic syndrome.
  
  
  RESULTS
  Median circulating AHSG was lower (p < 0.01) in type-2 (0.22 g/l) and type-1 (0.16 g/l) diabetics as compared to non-diabetic CKD-5 patients (0.24 g/l). AHSG correlated with both total and truncal fat mass in type-2 diabetics (rho 0.37 and 0.39; p < 0.001, respectively), but not in type-1 diabetics or non-diabetics. Both SNPs significantly influenced circulating levels of AHSG, and were also associated with significant differences in serum triglycerides and HDL cholesterol. Furthermore, there were significant differences in the prevalence of metabolic syndrome criteria between the AHSG Thr256Ser (C-G) genotype groups, with a more atherogenic lipid profile in AHSG high producers (Thr/Thr homozygotes). In multivariate analysis, the association between circulating AHSG and fat mass remained significant also after adjustment for age, gender, inflammation (CRP >10 mg/l), and AHSG genotype.
  
  
  CONCLUSIONS
  The present, explorational, study supports further, mechanistic, studies into a physiological link between AHSG and body fat mass in patients with CKD. As we observed an association between higher fat mass and elevated AHSG levels, these preliminary results may form the basis of further study to establish if the observed associations may be one reason why obesity has been reported to constitute a survival advantage in CKD.
authors.affiliation: Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. jonas.axelsson@ki.se
authors.forename: Jonas
authors.initials: J
authors.lastname: Axelsson
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Markus
authors.initials: M
authors.lastname: Ketteler
authors.forename: Abdul Rashid
authors.initials: AR
authors.lastname: Qureshi
authors.forename: Olof
authors.initials: O
authors.lastname: Heimbürger
authors.forename: Peter
authors.initials: P
authors.lastname: Bárány
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindholm
authors.forename: Louise
authors.initials: L
authors.lastname: Nordfors
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology; D001798:Blood Proteins / Q000032:analysis* / Q000235:genetics; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D008875:Middle Aged; D009765:Obesity / Q000097:blood; D011110:Polymorphism, Genetic; D060749:alpha-2-HS-Glycoprotein; D000509:alpha-Fetoproteins / Q000032:analysis*
chemical_list: C556354:AHSG protein, human; D001798:Blood Proteins; D060749:alpha-2-HS-Glycoprotein; D000509:alpha-Fetoproteins