The present study was conducted to screen serum exosomal microRNAs (miRNAs) for the early diagnosis of Kawasaki disease (KD) and to investigate their underlying mechanisms by analyzing microarray data under accession numbers GSE60965 [exosomal miRNA, including three pooled serum samples from 5 healthy children, 5 patients with KD and 5 patients with KD following intravenous immunoglobulin (IVIG) therapy] and GSE73577 (mRNA, including peripheral blood mononuclear cell samples from 19 patients with KD prior to and following IVIG treatment) from the Gene Expression Omnibus database. Differentially expressed miRNAs (DE-miRNAs) and genes (DEGs) were identified using the Linear Models for Microarray data method, and the mRNA targets of DE-miRNAs were predicted using the miRWalk 2.0 database. The functions of the target genes were analyzed using the Database for Annotation, Visualization and Integrated Discovery (DAVID). As a result, 65 DE-miRNAs were identified with different expression patterns between the healthy children and patients with KD and between patients with KD and patients with KD following IVIG therapy. The target genes of 15 common DE-miRNAs were predicted. Following overlapping the target genes of DE-miRNAs with 355 DEGs, 28 common genes were identified and further screened to construct a network containing 30 miRNA-mRNA regulatory associations. Of these associations, only miR-328-spectrin α, erythrocytic 1, miR-575-cyclic AMP-responsive element-binding protein 5/b-1,4-galactosyltransferase 5/WD repeat and FYVE domain-containing 3/cystatin-A/C-X-C motif chemokine receptor 1/protein phosphatase 1 regulatory subunit 3B, miR-134-acyl-CoA synthetase long chain family member 1/C-type lectin domain family 1 member A and miR-671-5p-tripartite motif containing 25/leucine rich repeat kinase 2/kinesin family member 1B/leucine rich repeat neuronal 1 were involved in the negative regulation of gene expression. Functional analysis indicated that the identified target genes may be associated with inflammation. Accordingly, serum exosomal miR-328, miR-575, miR-134 and miR-671-5p may act as potential biomarkers for the diagnosis of KD and the prediction of outcomes of the IVIG therapy by influencing the expression of inflammatory genes.

• Kawasaki disease
• biomarker
• exosome
• inflammatory
• intravenous immunoglobulin
• microRNA
• vasculitis

Background. Cardiovascular morbidity and mortality are very high in patients with chronic kidney disease (CKD). The purpose of this study is to evaluate the impact of continuous erythropoietin receptor activator (CERA) on selected biomarkers of cardiovascular disease, left ventricle structure, and function in CKD. Material and Methods. Peripheral blood was collected from 25 CKD patients before and after CERA treatment and 20 healthy subjects. In serum samples, we assessed inflammatory markers (IL-1β, TNF-RI, TNF-RII, sFas, sFasL, MMP-9, TIMP-1, and TGF-β1), endothelial dysfunction markers (sE-selectin, sICAM-1, and sVCAM-1), and volume-related marker (NT-proBNP). All subjects underwent echocardiography and were evaluated for selected biochemical parameters (Hb, creatinine, and CRP). Results. Evaluated biomarkers and echocardiographic parameters of left ventricle structure were significantly increased but left ventricle EF was significantly decreased in CKD patients compared to controls. After CERA treatment, we observed a significant increase of Hb and left ventricle EF and a significant decrease of NT-proBNP and MMP-9. There was a significant negative correlation between Hb and TNF-RI, sICAM-1, and IL-1β. Conclusions. Our results indicate that selected biomarkers related to cardiovascular risk are significantly increased in CKD patients compared to controls. CERA treatment has anti-inflammatory action, diminishes endothelial dysfunction, and improves left ventricle function in these patients.

• Chronic renal failure
• Cytokines pro-inflammatoires
• Homocystéine totale
• Insuffisance rénale chronique
• Oxidative status
• Pro-inflammatory cytokines
• Statut oxydant/antioxydant
• Total homocysteine

• Adult
• Aged
• Biomarkers/blood
• Cytokines/blood
• Female
• Homocysteine/blood
• Humans
• Interleukin-1beta/blood
• Interleukin-6/blood
• Kidney Failure, Chronic/blood
• Kidney Failure, Chronic/diagnosis
• Kidney Failure, Chronic/physiopathology
• Male
• Middle Aged
• Oxidative Stress
• Predictive Value of Tests
• Sensitivity and Specificity
• Severity of Illness Index
• Tumor Necrosis Factor-alpha/blood

AIM: To evaluate determinants of inflammatory markers in chronic renal failure patients according to the level of glomerular filtration rate.

METHODS: One hundred fifty four patients (Age: 44 ± 06 years; male/female: 66/88) with chronic renal failure (CRF) were divided into 6 groups according to the National Kidney Foundation (NKF) classification. They included 28 primary stage renal failure patients (CRF 1), 28 moderate stage renal failure patients (CRF 2), 28 severe stage renal failure patients (CRF 3), 18 end-stage renal failure patients (CRF 4), 40 hemodialysis (HD) patients, and 12 peritoneal dialysis (PD) patients. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and C-reactive protein (CRP) were analyzed by immunosorbent assay kit (ELISA) (Cayman Chemical’s ACETM EIA kit). Immunoassay methods were used for total homocysteine (tHcy) (fluorescence polarization immunoanalysis HPLC, PerkinEmer 200 series), transferrin (MININEPHTM human transferin kit: ZK070.R), ferritin (ADVIA Centaur) and fibrinogen analysis (ACL 200). Differences between groups were performed using SPSS 20.0 and data are expressed as the mean ± SD.

RESULTS: Results showed that in comparison with CRF 1 group and other groups, TNF-α and IL-6 levels were respectively more elevated in HD (16.38 ± 5.52 pg/mL vs 0.39 ± 0.03 pg/mL, 11.05 ± 3.59 pg/mL vs 8.20 ± 0.22 pg/mL, P < 0.001) and PD (14.04 ± 3.40 pg/mL vs 0.39 ± 0.03 pg/mL, 10.15 ± 1.66 pg/mL vs 8.20 ± 0.22 pg/mL, P < 0.001). IL-1β levels were increased in HD (9.63 ± 3.50 pg/mL vs 3.24 ± 0.10 pg/mL, P < 0.001) and CRF 4 (7.76 ± 0.66 pg/mL vs 3.24 ± 0.10 pg/mL, P < 0.001) patients than in CRF 1 and in the other groups. Plasma tHcy levels were higher in HD (32.27 ± 12.08 μmol/L) and PD (28.37 ± 4.98 μmol/L) patients compared to the other groups of CRF (P < 0.001). The serum CRP level was significantly increased in HD (18.17 ± 6.38 mg/L) and PD (17.97 ± 4.85 mg/L) patients compared to the other groups of CRF patients (P < 0.001). The plasma fibrinogen level was more elevated in HD (6.86 ± 1.06 g/L) and CRF 4 (6.05 ± 0.57 g/L) than in the other groups (P < 0.001). Furthermore; the ferritin level was higher in HD (169.90 ± 62.16 ng/mL) and PD (90.08 ± 22.09 ng/mL) patients compared to the other groups of CRF (P < 0.001). The serum transferrin value was significantly decreased especially in PD (1.78 ± 0.21 g/L) compared to the other groups (P < 0.001). We found a negative correlation between glomerular filtration rate (GFR), TNF-α levels (r = -0.75, P < 0.001), and tHcy levels (r = -0.68, P < 0.001). We observed a positive correlation between GFR and transferrin levels (r = 0.60, P < 0.001).

CONCLUSION: CRF was associated with elevated inflammatory markers. The inflammation was observed at the severe stage of CRF and increases with progression of renal failure.

• Chronic renal failure
• Inflammation
• Pro-inflammatory cytokines
• Total homocysteine
• Glomerular filtration rate