Chronic kidney disease (CKD) is a worldwide public health problem that affects millions of people from all racial and ethnic groups. Although CKD is not one specific disease, it is a comprehensive syndrome that includes IgA nephropathy. As reported by the Japanese Society of Nephrology, 13.0 million people have CKD. In Japan, major causes of end-stage kidney disease are type 2 diabetic nephropathy, chronic glomerulonephritis, especially IgA nephropathy, hypertensive nephrosclerosis, and polycystic kidney disease. IgA nephropathy is characterized by polymeric IgA1 with aberrant galactosylation (galactose-deficient IgA1) increased in the blood and deposited in the glomerular mesangial areas, as well as partially in the capillary walls. The tonsils are important as one of the responsible regions in this disease. The clarification of the mechanism of galactose-deficient IgA1 production will pave the way for the development of novel therapies. The results of future research are eagerly awaited. At present, the most important therapeutic goals in patients with IgA nephropathy are the control of hypertension, the decrease of urinary protein excretion, and the inhibition of progression to end-stage kidney disease. Several investigators have reported that renin–angiotensin–aldosterone system inhibitors reduce levels of urinary protein excretion and preserve renal function in patients with IgA nephropathy. In Japan, tonsillectomy and steroid pulse therapy are more effective for patients with IgA nephropathy.
Asian Continental Ancestry Group ; Capillaries ; Diabetic Nephropathies ; Diagnosis* ; Ethnic Groups ; Glomerulonephritis ; Glomerulonephritis, IGA* ; Humans ; Hypertension ; Immunoglobulin A* ; Japan* ; Kidney Failure, Chronic ; Nephrology ; Nephrosclerosis ; Palatine Tonsil ; Polycystic Kidney Diseases ; Polymers ; Public Health ; Renal Insufficiency, Chronic ; Research Personnel ; Tonsillectomy

Objective To elucidate the effects of eicosapentaenoic acid(EPA)on the metabolic abnormalities and renal pathologic changes during the early stage of diabetic nephropathy in KKAy/Ta mice.Methods Sixteen KKAy/Ta mice(7 weeks of age)were randomly divided into two groups(n=8).Since 12 weeks of age,EPA group were injected with EPA at 1 g?kg-1?d-1 intraperitoneally for 8 weeks,and the control group were injected with 0.9% saline.The levels of serum fatty acids were detected at 20 weeks of age by gas chromatography.The phenotypic characterizations were measured at 12,16 and 20 weeks of age.Renal morphological examinations were performed after 8 weeks of treatment.Results Serum EPA levels in KKAy/Ta mice treated with EPA [(125.8?15.5)?g/mL] were significantly higher than those in control group [(69.2?7.8)?g/mL] at 20 weeks of age(P

ObjectiveTo investigate whether advanced glycation end products (AGE) induce monocyte chemoattractant protein-1 (MCP-1) expression in mouse podocytes in vitro and the role of AGE receptor (RAGE). MethodsThe effects of AGE, CML, S100 protein and neutralizing antibody against RAGE on MCP-1 gene and protein expressions were examined by RT-PCR and ELISA in mouse podocytes. ResultsRAGE was detected in undifferentiated and differentiated podocytes. AGE and CML dose-dependently stimulated MCP-1 expression in podocytes. At 8 h of incubation, AGE-and CML-treated podocytes produced more MCP-1 than that treated with bovine serum albumin (BSA), the MCP-1 concentrations being (7.44?1.01 and 8.06?0.96)ng/L for AGE and CML respectively vs (3.77?0.39)ng/L for BSA (both P

Objective To investigate the signalling events follow the activation of RAGE in podocytes. Methods AGE and CML generated dichloroflurescin-sensitive intracellular ROS were measured by confocal microscopy. The activation of MAP kinases family were studied using Western blotting. MCP-1 mRNA expression was detected by semi-quantitative RT-PCR. Results Basal ROS was located in nucleus of starvation podocytes. AGE and CML rapidly generated intracellular ROS in podocytes. NAC pre-treated podocytes suppressed basal and inducible ROS generation and antibody for RAGE suppressed the inducible ROS. Blockage of ROS induced by NAC suppressed the expression of CML and H_2O_2-induced MCP-1. Phosphorylated extracellular signal-regulated kinase (ERK) was found in CML incubated podocytes at 10 min and was prevented by NAC or AFC. PD98058 Pre-treated podocytes partially inhibited the expression of CML-induced MCP-1 mRNA. No evidence were showed that p38 MAPK, SAPK/JNK, PI3K and PKC were involved in the signal transduction. Conclusion Activation of RAGE induces MCP-1 expression in podocytes via ROS-ERK signalling pathway.

BACKGROUND: IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis worldwide. Tonsillectomy plus steroid pulse therapy has been able to induce clinical remission in early-stage IgAN. However, its possible effect on systemic and local cytokines and tubular markers has not been fully investigated. METHODS: We obtained serum and urine samples from 38 patients just before renal biopsy and third steroid pulse therapy. Markers of tubular damage such as N-acetyl-β-d-glucosaminidase, and kidney injury molecule-1 and inflammation such as interleukin (IL)-6, monocyte chemotactic protein (MCP)-1, intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 were measured by immunoassay. RESULTS: Before renal biopsy, only urinary inflammatory markers, except MCP-1, were associated with glomerular (proteinuria) and/or tubular damage markers. Proteinuria, hematuria, and estimated glomerular filtration rate dramatically improved after therapy. In addition, levels of serum IL-6 and ICAM-1 and all urinary markers declined significantly; however, serum MCP-1 and VCAM-1 levels did not. None of the urinary markers correlated with the serum inflammatory markers. CONCLUSION: Tonsillectomy plus steroid pulse therapy for patients with IgAN might be useful for improving not only glomerular damage marker but also tubular damage markers through the improvement of local renal inflammation.
Biopsy ; Cytokines ; Glomerular Filtration Rate ; Glomerulonephritis ; Glomerulonephritis, IGA* ; Hematuria ; Humans ; Immunoassay ; Immunoglobulin A* ; Inflammation ; Intercellular Adhesion Molecule-1 ; Interleukin-6 ; Interleukins ; Kidney ; Monocytes ; Proteinuria ; Tonsillectomy* ; Vascular Cell Adhesion Molecule-1