FP559ELEVATED CIRCULATING S100A12 ASSOCIATES WITH VASCULAR DISEASE AND CLINICAL OUTCOME IN PERITONEAL DIALYSIS PATIENTS

Abstract

Introduction and Aims: The pro-inflammatory receptor of advanced glycation end-products (RAGE)-ligand S100A12 is thought to promote whereas anti-inflammatory soluble RAGE (sRAGE) may protect against vascular disease. We evaluated circulating S100A12 and sRAGE in relation to vascular disease, inflammation, nutritional status and mortality risk in peritoneal dialysis (PD) patients. Methods: Plasma S100A12 and sRAGE, biomarkers of inflammation, nutritional status, and comorbidities were analyzed in 82 PD patients (median age of 65 years, 70% men and median dialysis vintage time of 12 [6 to 29] months) and, for comparative analysis, also in 190 hemodialysis (HD) patients and 50 community-dwelling control subjects. During follow-up for up to 5 years, 23 PD patients died, and 19 underwent renal transplantation. Associations between mortality risk and concentrations of S100A12 and sRAGE were assessed in PD patients after a mean follow-up period of 31 months. Competing risk analysis analysis, taking into account kidney transplantation, was used to calculate mortality risk. Results: S100A12, sRAGE and the ratio S100A12/sRAGE were markedly higher in PD patients than in controls, and the median ratio S100A12/sRAGE was 2.4 times higher in PD patients than in HD patients. In PD patients, S100A12 associated with C-reactive protein (ρ=0.46; P<0.001) and interleukin-6, IL-6 (ρ=0.38; P<0.001), and, negatively, with albumin (ρ=-0.27; P<0.05) whereas sRAGE associated negatively with body mass index (ρ=-0.37; P<0.001), fat body mass index (ρ=-0.34; P<0.001), and lean body mass index (ρ=-0.36; P<0.001). Median S100A12 at baseline was higher in 23 non-survivors (36 [11-62] ng/ml, P<0.05) than in 59 survivors who remained on PD (23 [16-31] ng/ ml) or underwent renal transplantation (29 [23-54] ng/ml), and the highest tertile of S100A12 associated with increased mortality risk, see figure. In HD patients we found similar findings. In contrast, sRAGE was not associated with mortality in PD patients. Peripheral vascular disease or cerebrovascular disease (PCVD) was present in 28% of the PD patients. Presence of PCVD associated with history of CVD, lower s-albumin, higher IL-6 and higher S100A12. Multivariate logistic regression analysis showed that PCVD associated mainly with high S100A12 (Odds ratio; 3.52, p=0.04). Conclusions: Plasma S100A12 and sRAGE, and the ratio S100A12/sRAGE, are markedly elevated in PD patients. sRAGE was inversely related to body mass indices while S100A12 associated with mortality, inflammation and presence of PCVD, suggesting that S100A12 may be a biomarker that could identify PD patients at high risk for vascular disease. (Figure Presented).