Plasma S100A12 and soluble receptor of advanced glycation end product levels and mortality in chronic kidney disease Stage 5 patients

Background. Alterations in the advanced glycation end-products (AGE)—receptor of AGE (RAGE) system are linkedto several chronic diseases, which may result from vasculardamage. A high circulating level of the pro-inflammatoryRAGE-ligand S100A12, also known as EN-RAGE, is thoughtto promote while a high level of soluble RAGE (sRAGE) isthought to protect against development of atherosclerotic car-diovascular disease (CVD). We evaluated circulating S100A12and sRAGE in relation to clinical characteristics, nutritionalstatus, inflammation and mortality risk in chronic kidneydisease (CKD) Stage 5 patients starting on dialysis.Methods. Plasma S100A12 and sRAGE, biomarkers of inflam-mation and nutritional status, and comorbidities were investi-gated in 200 CKD Stage 5 patients [median age of 56 years,62% men and median glomerular filtration rate (GFR) of6.2 mL/min/1.73 m 2 ] in conjunction with initiation of dialysistherapy. Associations between mortality risk and S100A12 orsRAGE were assessed after a median follow-up period of23 months. In addition, for comparative analyses, S100A12and sRAGE levels were assessed also in 58 haemodialysis and78 peritoneal dialysis patients after 1 year of dialysis, 56 CKDStages 3–4 patients and 50 community-based control subjects.Results. The median level of S100A12 was 4-fold higher, mediansRAGE 2.4 higher and median ratio S100A12/sRAGE 2.27 timeshigher in CKD 5 patients than in controls. Similar alterationswere observed in CKD 3–4 patients; however, CKD 5 patientshad a higher median level of sRAGE than the CKD 3 –4patients.In the CKD 5 patients, S100A12 levels were higher in those withdiabetes or CVD than in those without these comorbidities. Fur-thermore, S100A12 correlated with high-sensitivity C-reactiveprotein (hsCRP) levels (ρ=0.53; P