title: Associations between Soluble Receptor for Advanced Glycation End Products (sRAGE) and S100A12 (EN-RAGE) with Mortality in Long-term Hemodialysis Patients.
abstract: Hemodialysis (HD) patients experience vascular calcification, ultimately leading to high mortality rates. Previously, we reported associations between soluble receptor for advanced glycation end products (sRAGEs) and extracellular newly identified RAGE-binding protein S100A12 (EN-RAGE) and vascular calcification. Here, we extended our observations, investigating whether these biomarkers may be useful for predicting cardiovascular morbidity and mortality in these subjects. Thus, we evaluated the relationship between sRAGE and S100A12 and mortality in long-term HD patients. This was a prospective observational cohort study in 199 HD patients from an extended analysis of our previous study. Plasma sRAGE, S100A12, comorbidities, and other traditional risk factors were investigated. The cumulative incidences for death using Cox proportional hazards regression were evaluated in multivariable analyses. The observation period was 44 months. During the observation period, 27 (13.6%) patients died. Univariate analysis demonstrated that S100A12 was correlated with diabetes (P = 0.040) and high-sensitivity C-reactive protein (hsCRP) (P = 0.006). In multivariable analyses, plasma sRAGE (hazard ratio [HR] = 1.155; 95% confidence interval [CI] = 0.612-2.183; P = 0.656) and S100A12 (HR = 0.960; 95% CI = 0.566-1.630; P = 0.881) were not associated with mortality in HD patients, although traditional predictors of mortality, including age, history of cardiovascular diseases (CVDs), and serum levels of albumin and hsCRP were related to mortality. Powerful predictors of mortality were age, CVD, and albumin levels. Plasma sRAGE and S100A12 may be weak surrogate markers for predicting all-cause mortality in patients undergoing HD, although S100A12 was partly related to diabetes and inflammation.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.
authors.forename: Eul Sik
authors.identifier: http://orcid.org/0000-0003-3898-4693
authors.initials: ES
authors.lastname: Jung
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.|Division of Nephrology, Department of Internal Medicine, Gachon University School of Medicine, Incheon, Korea.
authors.forename: Wookyung
authors.identifier: http://orcid.org/0000-0001-7657-130X
authors.initials: W
authors.lastname: Chung
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.|Division of Nephrology, Department of Internal Medicine, Gachon University School of Medicine, Incheon, Korea.
authors.forename: Ae Jin
authors.identifier: http://orcid.org/0000-0001-5017-8649
authors.initials: AJ
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.|Division of Nephrology, Department of Internal Medicine, Gachon University School of Medicine, Incheon, Korea.
authors.forename: Han
authors.identifier: http://orcid.org/0000-0001-7170-0571
authors.initials: H
authors.lastname: Ro
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.|Division of Nephrology, Department of Internal Medicine, Gachon University School of Medicine, Incheon, Korea.
authors.forename: Jae Hyun
authors.identifier: http://orcid.org/0000-0003-3947-0715
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.|Division of Nephrology, Department of Internal Medicine, Gachon University School of Medicine, Incheon, Korea.
authors.forename: Hyun Hee
authors.identifier: http://orcid.org/0000-0002-0319-6390
authors.initials: HH
authors.lastname: Lee
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Korea.|Division of Nephrology, Department of Internal Medicine, Gachon University School of Medicine, Incheon, Korea. jyjung@gachon.ac.kr.
authors.forename: Ji Yong
authors.identifier: http://orcid.org/0000-0003-1271-8012
authors.initials: JY
authors.lastname: Jung
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D012307:Risk Factors; D000067616:S100A12 Protein / Q000097:blood*; D012709:Serum Albumin / Q000032:analysis; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D000067616:S100A12 Protein; D012709:Serum Albumin; D002097:C-Reactive Protein
keywords: Hemodialysis; Mortality; S100A12; sRAGE