title: Circulating levels of soluble receptor for advanced glycation end product are inversely associated with vascular calcification in patients on haemodialysis independent of S100A12 (EN-RAGE) levels.
abstract: OBJECTIVE
  The receptor for advanced glycation end products (RAGE) has emerged as a central regulator of vascular inflammation and atherosclerosis. Soluble RAGE (sRAGE) has an anti-inflammatory effect by quenching ligands for RAGE. On the other hand, extracellular RAGE-binding protein S100A12 (EN-RAGE) shows a pro-inflammatory effect in a way, but may play pleiotropic roles related to inflammatory process. Therefore, we determined the levels of sRAGE and S100A12 in haemodialysis (HD) patients and evaluated their relationship with vascular calcification.
  
  
  METHODS
  We performed a cross-sectional study with 199 HD patients. Plain X-ray images of the lateral lumbar spine from all subjects were studied to calculate semiquantitative vascular calcification scores (VCS), as described by Kauppila. Commercially available enzyme linked immunosorbent assay (ELISA) kits were used to quantify the serum concentration of sRAGE and S100A12.
  
  
  RESULTS
  The patients were 57.1 ± 13.7 years of age; 54.3% were male, 49.2% were diabetic, and 36.2% had a history of cardiovascular disease. In a univariate analysis, serum sRAGE was negatively associated with VCS (log sRAGE, r=-0.208, P=0.003), whereas S100A12 showed a positive tendency (log S100A12, r=0.235, P=0.085). Even after adjustments for confounding risk factors, sRAGE was independently associated with VCS (β=-1.679, P=0.002).
  
  
  CONCLUSIONS
  This study demonstrated that the circulating sRAGE level was inversely associated with VCS in HD patients independent of the S100A12 level and the severity of systemic inflammation.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University of Medicine and Science, Incheon, Korea.
authors.forename: Hyung Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Wookyung
authors.initials: W
authors.lastname: Chung
authors.forename: Ae Jin
authors.initials: AJ
authors.lastname: Kim
authors.forename: Han
authors.initials: H
authors.lastname: Ro
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Chang
authors.forename: Hyun Hee
authors.initials: HH
authors.lastname: Lee
authors.forename: Ji Yong
authors.initials: JY
authors.lastname: Jung
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D003928:Diabetic Nephropathies / Q000097:blood; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood* / Q000502:physiology; D006435:Renal Dialysis; D009418:S100 Proteins / Q000097:blood* / Q000502:physiology; D000067616:S100A12 Protein; D061205:Vascular Calcification / Q000097:blood*
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human
keywords: S100A12; haemodialysis; soluble receptor for advanced glycation end product; vascular calcification