title: Effect of circulating soluble receptor for advanced glycation end products (sRAGE) and the proinflammatory RAGE ligand (EN-RAGE, S100A12) on mortality in hemodialysis patients.
abstract: OBJECTIVE
  The soluble receptor of advanced glycation end products (sRAGE) may exert anti-inflammatory protective roles on the vasculature. In contrast, the RAGE ligand S100A12 (also known as EN-RAGE) contributes to inflammation and the development of atherosclerosis in animal models. Whether alterations at this level contribute to the increased mortality observed in patients on dialysis is currently unknown.
  
  
  METHODS
  Prospective study including 184 prevalent hemodialysis patients and 50 healthy controls matched for age and gender. Plasma concentrations of S100A12 and sRAGE were studied in relation to risk profile and mortality after a median follow-up period of 41 months.
  
  
  RESULTS
  S100A12 and sRAGE levels were significantly elevated in hemodialysis patients compared with healthy controls. S100A12 had a strong positive correlation with C-reactive protein and IL-6, whereas sRAGE negatively associated with C-reactive protein. S100A12, but not sRAGE, was independently and positively associated with clinical cardiovascular disease (CVD). During follow-up, 85 (33 cardiovascular-related) deaths occurred. Whereas sRAGE did not predict mortality, S100A12 was associated with both all-cause (per log(10) ng/ml hazard ratio [HR] 1.93, 95% confidence interval [CI] 1.18 to 3.15) and CVD-related (HR 3.23, 95% CI 1.48 to 7.01) mortality, even after adjustment for age, sex, vintage, and comorbidities. Further adjustment for inflammation made the predictive value of S100A12 disappear for all-cause mortality, but still persisted in CVD-related mortality.
  
  
  CONCLUSIONS
  Circulating S100A12 and sRAGE are both elevated in hemodialysis patients. However, only S100A12 associates with mortality, partly explained by its links with inflammation.
authors.affiliation: Division of Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Nakashima
authors.forename: Juan Jesús
authors.initials: JJ
authors.lastname: Carrero
authors.forename: Abdul Rashid
authors.initials: AR
authors.lastname: Qureshi
authors.forename: Tetsu
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Björn
authors.initials: B
authors.lastname: Anderstam
authors.forename: Peter
authors.initials: P
authors.lastname: Bárány
authors.forename: Olof
authors.initials: O
authors.lastname: Heimbürger
authors.forename: Peter
authors.initials: P
authors.lastname: Stenvinkel
authors.forename: Bengt
authors.initials: B
authors.lastname: Lindholm
mesh_terms: D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood; D006801:Humans; D015999:Multivariate Analysis; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D006435:Renal Dialysis / Q000401:mortality*; D009418:S100 Proteins / Q000097:blood*; D000067616:S100A12 Protein
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D002097:C-Reactive Protein