Plasma levels of soluble receptor for advanced glycation end products (sRAGE) and proinflammatory ligand for RAGE (EN-RAGE) are associated with carotid atherosclerosis in patients with peritoneal dialysis

Atherosclerosis. 2012 Jan;220(1):208-14. doi: 10.1016/j.atherosclerosis.2011.07.115. Epub 2011 Aug 5.


Objectives: The soluble receptor for advanced glycation end products (sRAGE) exerts a protective effect on the development of atherosclerotic vascular complications by inhibiting RAGE-mediated inflammatory response. In contrast, extracellular newly identified RAGE-binding protein (EN-RAGE) contributes to increased atherosclerosis as a pro-inflammatory ligand for RAGE. We determined the levels of sRAGE and EN-RAGE in peritoneal dialysis (PD) patients and evaluated their relationship with carotid atherosclerosis.

Methods: A cross-sectional study was performed in 91 PD patients and 29 control subjects. Carotid IMT (cIMT) and abdominal aortic vascular calcification score (VCS) were evaluated using high-resolution B-mode ultrasonography and plain radiographic film of the lateral abdomen.

Results: Plasma sRAGE and EN-RAGE levels were more than twice as higher in PD patients compared to controls. EN-RAGE showed a strong positive correlation with serum high-sensitivity CRP (p=0.007) and IL-6 (p=0.002), whereas sRAGE was negatively associated with those inflammatory markers (p=0.001, p=0.031). Even after adjustments for traditional cardiovascular risk factors, both sRAGE and EN-RAGE were independently associated with cIMT (β=-0.230, p=0.037, β=0.155, p=0.045) and VCS (β=-0.205, p=0.049, β=0.197, p=0.156). Multivariate logistic analysis revealed that old age (OR 1.14, 95% CI 1.03-1.25, p=0.009), presence of diabetes (OR 13.4, 95% CI: 1.20-150.18, p=0.035) and elevated plasma EN-RAGE (OR 2.26, 95% CI: 1.05-5.11, p=0.048) were significant predictors for the occurrence of carotid atherosclerosis (cIMT>1.0mm and/or plaque formation).

Conclusions: Our findings suggest that elevated plasma EN-RAGE and decreased sRAGE level could play a crucial role in systemic inflammation and carotid atherosclerosis in PD patients.

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Aorta, Abdominal / diagnostic imaging
  • Aortic Diseases / diagnostic imaging
  • Aortic Diseases / immunology
  • Aortography
  • Biomarkers / blood
  • Carotid Artery Diseases / blood
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / immunology*
  • Carotid Intima-Media Thickness
  • Case-Control Studies
  • Cross-Sectional Studies
  • Female
  • Humans
  • Inflammation Mediators / blood*
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / immunology
  • Kidney Failure, Chronic / therapy*
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Peritoneal Dialysis / adverse effects*
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / blood*
  • Republic of Korea
  • Risk Assessment
  • Risk Factors
  • S100 Proteins / blood*
  • S100A12 Protein
  • Vascular Calcification / diagnostic imaging
  • Vascular Calcification / immunology


  • Biomarkers
  • Inflammation Mediators
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • S100 Proteins
  • S100A12 Protein
  • S100A12 protein, human