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

Isoyama, Naohito; Leurs, Paul; Qureshi, Abdul Rashid; Bruchfeld, Annette; Anderstam, Björn; Heimbürger, Olof; Bárány, Peter; Stenvinkel, Peter; Lindholm, Bengt

doi:10.1093/ndt/gfu259

Cited by 57 publications

(56 citation statements)

References 43 publications

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“…We report the novel findings that high S100A12 associates with mortality in prevalent PD patients-similar to observations in CKD stage-5 patients starting on dialysis (17) and prevalent HD patients (18)-and that S100A12 associates with biomarkers of inflammation and presence of PCVD, suggesting that the mortality-predictive role of S100A12 is linked to vascular disease involving inflammatory mediators.…”

Section: Discussionsupporting

confidence: 75%

“…In uremia, increased formation and accumulation of AGEs result in up-regulation of RAGE linked to interstitial peritoneal fibrosis and vascular sclerosis (25), and exposure to high glucose PD fluids may further contribute to such changes (26). Not surprisingly, sRAGE and S100A12 accumulate in PD patients (15)(16)(17), as shown also in the current study, and hyperglycemia-induced reactive oxygen species may further increase expression of RAGE and RAGE-ligands (27). As we found an inverse relation of S100A12, but not of sRAGE, with solute removal indices (GFR and KT/V), this may suggest that S100A12 is removed by the kidneys or that better metabolic control of uremia linked to residual renal function or dialytic removal of toxins result in lower plasma S100A12.…”

Section: Discussionmentioning

confidence: 99%

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Elevated Circulating S100A12 Associates with Vascular Disease and Worse Clinical Outcome in Peritoneal Dialysis Patients

et al. 2016

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♦ Background: 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 prevalent PD patients (median age 65 years; 70% men; median vintage 12 months) and, for comparative analysis, also in 190 hemodialysis (HD) patients and 50 control subjects. Associations between mortality risk and concentrations of S100A12 and sRAGE were assessed in PD and HD patients after a mean follow-up period of 31 and 29 months respectively using a competing risk Cox regression model. ♦ Results: In PD patients, median S100A12, sRAGE and S100A12/ sRAGE were markedly higher than in controls, and S100A12 was 1.9 times higher and median sRAGE 14% lower compared with HD patients. In PD patients, S100A12 associated with C-reactive protein (ρ = 0.46; p < 0.001) and interleukin-6 (ρ = 0.38; p < 0.001), and, negatively, with s-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). Peripheral vascular disease or cerebrovascular disease (PCVD) was present in 28% of PD patients and, in multivariate analysis, associated mainly with high S100A12 (odds ratio [OR] 3.52, p = 0.04). In both PD and HD patients, the highest versus other tertiles of S100A12 associated with increased mortality. In contrast, sRAGE did not associate with PCVD or mortality in PD and HD patients. ♦ Conclusions: Plasma S100A12 and sRAGE are markedly elevated in PD patients. Soluble RAGE was inversely related to body mass indices while S100A12 associated with increased inflammation, PCVD, and mortality, suggesting that S100A12 may identify PD patients at high risk for vascular disease and increased mortality.

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Section: Discussionsupporting

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Elevated Circulating S100A12 Associates with Vascular Disease and Worse Clinical Outcome in Peritoneal Dialysis Patients

et al. 2016

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“…It was proposed that the S100B/RAGE axis might play a role in SVD affecting deep brain regions by inducing inflammatory response, BBB dysfunction, and microbleeds in acute lacunar stroke [117,118]. While sRAGE association with microbleeds has not been examined in the CKD population, sRAGE levels are 2.4-fold higher in patients with advanced CKD, and the pro-inflammatory RAGE ligand S100A12 is fourfold higher as compared to non-CKD controls [119]. In 200 incident dialysis patients followed for ∼2 years, higher S100A12 levels correlated with inflammation and increased mortality risk [119].…”

Section: Cerebral Microbleedsmentioning

confidence: 99%

“…While sRAGE association with microbleeds has not been examined in the CKD population, sRAGE levels are 2.4-fold higher in patients with advanced CKD, and the pro-inflammatory RAGE ligand S100A12 is fourfold higher as compared to non-CKD controls [119]. In 200 incident dialysis patients followed for ∼2 years, higher S100A12 levels correlated with inflammation and increased mortality risk [119].…”

Section: Cerebral Microbleedsmentioning

confidence: 99%

Neurocritical Care for Patients with Kidney Dysfunction

Park¹

2017

J Neurocrit Care

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Chronic kidney disease (CKD) is an independent risk factor for the development of cerebrovascular disease, particularly small vessel disease which can manifest in a variety of phenotypes ranging from lacunes to microbleeds. Small vessel disease likely contributes to cognitive dysfunction in the CKD population. Nontraditional risk factors for vascular injury in uremia include loss of calcification inhibitors, hyperphosphatemia, increased blood pressure variability, elastinolysis, platelet dysfunction, and chronic inflammation. In this review, we discuss the putative pathways by which these mechanisms may promote cerebrovascular disease and thus increase risk of future stroke in CKD patients.

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“…21 Moreover, in a study of Isoyama et al 200 CKD patients are followed for median 23 months and increased concentration of S100A12 was found to be an independent predictor of mortality risk. 25 The aim of this study was to evaluate the association of plasma S100A12 level with carotid AS determined by measurement of carotid intima media thickness (CIMT) in PD patients.…”

Section: Introductionmentioning

confidence: 99%

Do elevated plasma S100A12 levels predict atherosclerosis in peritoneal dialysis patients?

et al. 2015

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Aim: Atherosclerotic cardiovascular disease is one of the major causes of mortality and morbidity in peritoneal dialysis (PD) patients. S100A12 is an endogenous receptor ligand of advanced glycation end-products. It was shown to contribute to the development of atherosclerosis in animal models. The aim of this study was to evaluate the relationship between S100A12 levels and carotid atherosclerosis in PD patients. Methods: A cross-sectional study was performed in 56 PD patients and 20 control subjects. Plasma S100A12 levels were measured from all participants beside routine laboratory evaluation. All subjects underwent high-resolution B-mode ultrasonography to determine carotid intima media thickness (CIMT). S100A12 levels were compared between patient and control groups. Correlation analyses of S100A12 with other laboratory values and CIMT were also performed. Results: Plasma S100A12 levels were higher in PD patients compared with control subjects (129.5 ± 167.2 ng/mL vs. 48.5 ± 30.3 ng/mL, respectively, p50.001). In the patient group, CIMT was found to be positively correlated with age (r ¼ 0.354; p ¼ 0.007), CRP level (r ¼ 0.269; p ¼ 0.045), and S100A12 (r ¼ 0.293; p ¼ 0.028) level while it was found to be negatively correlated with hemoglobin concentration (r ¼ À0.264; p ¼ 0.049). In the linear regression analysis, the model, including CRP, S100A12, age, and Hgb, was found to be significant (F: 4.177, p: 0.005). When the parameters are analyzed age and S100A12 were found to be independent determinants of CIMT ( ¼ 0.308, p ¼ 0.018 and ¼ 0.248, p ¼ 0.049, respectively). Conclusions: This study suggests that an elevated plasma S100A12 level was closely associated with atherosclerosis. With aging elevated plasma S100A12 may show a powerful proatherogenic potential in patients undergoing PD.

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

Cited by 57 publications

References 43 publications

Elevated Circulating S100A12 Associates with Vascular Disease and Worse Clinical Outcome in Peritoneal Dialysis Patients

Elevated Circulating S100A12 Associates with Vascular Disease and Worse Clinical Outcome in Peritoneal Dialysis Patients

Neurocritical Care for Patients with Kidney Dysfunction

Do elevated plasma S100A12 levels predict atherosclerosis in peritoneal dialysis patients?

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