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While β-hemolytic streptococcus (β-HS) infections are known to predispose patients to acute poststreptococcal glomerulonephritis, there is evidence that implicates α-hemolytic streptococcus (α-HS) in IgA nephropathy (IgAN). The alternative pathway of the complement system has also been implicated in IgAN. We aimed to explore the association between α-HS and complement activation in human tonsillar mononuclear cells (TMCs) in IgAN. In our study, α-HS induced higher IgA levels than IgG levels, while β-HS increased higher IgG levels than IgA levels with more activation-induced cytidine deaminase, in TMCs in the IgAN group. Aberrant IgA1 O-glycosylation levels were higher in IgAN patients with α-HS. C3 and C3b expression was decreased in IgAN patients, but in chronic tonsillitis control patients, the expression decreased only after stimulation with β-HS. Complement factor B and H (CFH) mRNA increased, but the CFH concentration in culture supernatants decreased with α-HS. The percentage of CD19 + CD35 + cells/complement receptor 1 (CR1) decreased with α-HS more than with β-HS, while CD19 + CD21 + cells/complement receptor 2 (CR2) increased more with β-HS than with α-HS. The component nephritis-associated plasmin receptor (NAPlr) of α-HS was not detected on tonsillar or kidney tissues in IgAN patients and was positive on cultured TMCs and mesangial cells. We concluded that α-HS induced the secretion of aberrantly O-glycosylated IgA while decreasing the levels of the inhibitory factor CFH in culture supernatants and CR1 + B cells. These findings provide testable mechanisms that relate α-HS infection to abnormal mucosal responses involving the alternative complement pathway in IgAN.

To examine whether platelet-to-lymphocyte ratio (PLR) is associated with 5-year mortality in patients with chronic kidney disease (CKD), we performed this study using data from the National Health and Nutrition Examination Survey (NHANES) through 1999 to 2006. 3285 patients with CKD stage 1–5 were included. Patients’ baseline characteristics were collected. Cox proportional hazards models were used to investigate the association of PLR with 5-year mortality including all-cause and cardiovascular mortality. Subgroup analysis was performed. Within 5 years following the date of the NHANES 1999 to 2006 survey participation, 655 (19.94%) deaths were recorded and 207 patients died from cardiovascular disease. A J-shaped association between PLR and 5-year mortality was observed. In adjusted model 2, the elevated PLR Z-score was not significantly associated with a decreased 5-year all-cause mortality risk (HR: 0.44, 95% CI: 0.16–1.22) when PLR Z-score

Background: Aberrant O-glycosylation IgA1 production is a major factor in the pathogenesis of IgA nephropathy, but the underlying mechanism is still unclear. IgA1 glycosylation modification is in Golgi, and downregulation of the Golgi peripheral membrane protein Golgi matrix protein 130 (GM130) could lead to glycosylation deficiency. In this study, we aimed to explore the role of GM130 in glycosylate deficiency IgA1 (Gd-IgA1) production. Methods: We enrolled 27 IgA nephropathy patients, 12 patients with chronic tonsillitis, 15 non-IgAN chronic kidney disease patients, and 15 healthy volunteers as healthy control. We explored GM130 expression in Tonsillar tissue by immunofluorescence staining and Western blotting and expression in peripheral blood mononuclear cells (PBMCs) by flow cytometry. The concentration of IgA1 and level of O-glycosylation were determined by ELISA and Vicia Villosa lectin-binding assay. Real-time PCR and Western blot were used to analyze the levels of β1,3-Gal transferase (C1GALT1) and ST6GalNAC2, respectively. To explore the contribution of GM130 in IgA1 O-glycosylation modification, cells were subjected to experiments for evaluation of GM130 silencing by GM130-siRNA transfection. Results: GM130 expression was significantly decreased in tonsil tissues and PBMC of IgAN patients; the expression of C1GALT1 decreased and Gd-IgA1 level increased significantly in patients with IgAN patients. The expression of GM130 was negatively related to Gd-IgA1 production. By siRNA transfection, our results clearly indicated that the downregulation of GM130 can increase IgA1 O-glycosylation deficiency, which is thought to reduce C1GALT1 expression but not affect the expression of ST6GalNAC2. Conclusion: We identified and demonstrated that GM130 plays an important role in IgA1 O-glycans deficiency in IgAN patients, by negatively regulating C1GALT1 expression. We believe that this finding will provide theoretical foundations for a new mechanism of Gd-IgA1 production in IgAN patients.

Background: Despite the progression of dialysis techniques, the mortality of hemodialysis (HD) patients is still high in China. Here, a retrospective study was performed to investigate the neglected risk factors of all-cause mortality during maintenance HD (MHD). Methods: We investigated 117 MHD patients who died between 2011 and 2016 in the Second Xiangya Hospital of Central South University HD center. In order to analyze the risk factors of 48 months all-cause death, the methods of Kaplan-Meier and Cox regression were used. Results: Multivariate analyses of adjusted age and gender showed that MHD patients with estimated glomerular filtration rate 10 mL/min/1.73 m2 and anemia (hemoglobin Conclusions: This study indicated that the status of HD initiation is a risk factor of long-term survival in MHD patients, which were usually ignored for lacking of nephrology care prior and could potentially be identified and modified to improve the survival prognosis. Video Journal Club “Cappuccino with Claudio Ronco” at https://www.karger.com/Journal/ArticleNews/223997?sponsor=52

IgA nephropathy (IgAN) is the most common primary glomerular disease. The characteristic pathology involves immune complexes formed by the deposition of IgA1 and underglycosylated IgA1 aggregates in the mesangial area, which may be accompanied by the deposition of IgG and/or IgM and complement components. However, the molecular mechanisms of IgAN remain unclear. In the present study, microarray analysis showed that the expression of microRNA-630 (miR-630) was significantly reduced in palatal tonsils from IgAN patients compared with chronic tonsillitis. Additionally, bioinformatic analysis showed that Toll-like receptor 4 (TLR4) was the predicted target gene of miR-630 and was regulated by miR-630. When miR-630 was overexpressed in palatal tonsil mononuclear cells from IgAN patients, the expression of TLR4 was reduced and the content of IgA1 in the cell culture supernatant was decreased, and the level of galactosylation in the IgA1 hinge region was increased. Moreover, immunohistochemical analysis showed that the expression of TLR4 in IgAN patients was significantly increased. After knocking down the expression of TLR4, both the concentration of IgA1 and the binding force of IgA1 with broad bean lectin were significantly reduced in IgAN. Furthermore, the mechanism study demonstrated that TLR4 might regulate the expression of IL-1β and IL-8 through NF-κB signaling pathway to modulate the concentration of IgA1 and the glycosylation level of IgA1. This interesting finding may offer new insight into the molecular mechanism of IgAN.

To examine whether albumin-to-globulin ratio (AGR) is correlated with long-term mortality in patients with chronic kidney disease (CKD), we performed this study using data from the National Health and Nutrition Examination Survey through 1999–2006. 3302 CKD patients were included. Patients’ baseline characteristics were collected. Multivariate Cox proportional hazards models were used to investigate the association between AGR and the study outcomes, including long-term all-cause and cardiovascular mortality. Subgroup analysis using the Cox proportional hazards model was performed as a sensitivity test. During a median follow-up duration of 122.00 months, 1627 (49.27%) deaths were recorded and 440 patients died from cardiovascular disease. In adjusted model 1, AGR ≥ 1.26 group was associated with a lower risk of long-term all-cause mortality HR 0.72, 95% CI 0.65–0.81) compared with AGR

Background/Aims: Tonsillectomy may be an important method to achieve a long-term remission of IgAN, but patients’ physical status may limit their access to this surgery. We proposed an encouraging solution through inhibiting GADD34 expression in order to promote tonsillar mononuclear cells (TMCs) apoptosis and reduce nephropathic IgA secretion. Methods: A total of 12 IgAN and 9 non-IgAN patients were involved from March 2015 to May 2016. After TMCs were extracted by density gradient centrifugation and stimulated by inactivated hemolytic streptococcus, the mRNA and protein expression of GADD34, GRP78, CHOP, Bcl-2, Bcl-XL, AID, Iα-Cα, and cleaved caspase-3 were examined by fluorescent RT-PCR and Western blotting. Guanabenz treatment and siRNA interference were applied to downregulate GADD34 in tonsillar mononuclear cells from IgAN patients, and P-eIF2α expression was examined by Western Blotting. Cell apoptosis was evaluated by Annexin V FITC/PI flowcytometry, and IgA secretion in cultural supernatant was inspected by enzyme linked immunosorbent assay. Results: After stimulation, the expression of GADD34 was significantly increased in IgAN patients (P< 0.05). Cell apoptosis was mitigated and IgA secretion level was elevated (P< 0.05). To be noticed, CHOP expression had no significant difference between two groups. After guanabenz treatment and siRNA interference, a prolonged elevation of P-eIF2α expression was observed. Cell apoptosis was reinforced and IgA secretion level was decreased (P< 0.05). Conclusion: GADD34 may be a potential therapeutic target for IgAN treatment due to its effect on cell apoptosis.

SUV39H1, the histone methyltransferase (HMTase) of histone H3 lysine 9 trimethylation (H3K9me3), is a known transcriptional repressor of inflammatory genes. The effect of SUV39H1 on inflammatory gene promoters under high-glucose stimulation in vascular smooth muscle cells (VSMCs), macrophages, and cardiomyocytes has been studied, but how SUV39H1 functions in renal tubules under diabetic conditions is unclear. Renal biopsy specimens of ten diabetic nephropathy (DN) subjects and seven non-DN minimal change diseases (MCD) subjects were collected. SUV39H1, IL-6, and MCP-1 expression in renal tissues were measured using immunohistochemical, while SUV39H1, H3K9me3, IL-6, and MCP-1 in human proximal tubular epithelial cells (HK-2) under varying glucose conditions were assayed by Western blot and ELISA. SUV39H1 was overexpressed in HK-2 cells; the regulation of SUV39H1 and H3K9me3 on NF-κB, IL-6, MCP-1, caspase 3, and apoptosis was measured. SUV39H1 was expressed more in diabetic human renal tubules. HK-2 cells with high glucose up-regulated IL-6 and MCP-1 in a dose- and time-dependent manner, and SUV39H1 expression was reduced with greater glucose and prolonged stimulation. Expression of H3K9me3 was synchronized with SUV39H1. Moreover, overexpression of SUV39H1 in high glucose environment was accompanied with increased H3K9me3 and decreased inflammation and apoptosis. SUV39H1 dysregulation may be involved in DN progression. Overexpression of SUV39H1 may reduce renal inflammation and apoptosis via epigenetic modulation, thus plays a protective role in DN.

Many studies have focused on finding predictors for mild IgAN progression. However, the cases of severe IgAN with a high proportion of global glomerulosclerosis have received inadequate attention.A group of 172 primary IgAN patients with 50-75% global glomerulosclerosis was studied retrospectively between April 2007 and October 2017. Patients were divided into three groups according to the serum triglyceride tertiles: 1.42 µmol/L (Group 1), 1.42-2.29 µmol/L (Group 2), and 2.29 µmol/L (Group 3). Groups 1 and 2 comprised non-hypertriglyceridemia subjects, while Group 3 was defined as the hypertriglyceridemia (HTG) group. The patients were followed for 4-96 months (median 39.43 months). The study end point was defined as a 50% decline in estimated glomerular filtration rate (eGFR) or ESRD.A high proportion of global glomerulosclerosis is not absolutely correlated with severe clinical features and poor renal outcome. In our retrospective observation, eGFR decreased by less than 10% of the baseline during follow-up in 43.6% of the patients. However, in our patients with HTG, the cumulative renal survival rate was significantly lower compared to those without HTG. Multivariate Cox regression analysis also showed that triglyceride is an independent predictor of poor renal outcomes. Furthermore, in the HTG group, the cumulative renal survival rates were higher in patients treated with Tripterygium wilfordii Hook F (TwHF) compared to those without TwHF.A high proportion of global glomerulosclerosis combined with HTG at biopsy have better predictive validity for the disease progression of IgAN than global glomerulosclerosis alone. TwHF may partially affect the renal outcome of severe IgAN with HTG, and this may relate to its regulation of lipid metabolism and immunoinflammatory response.

Introduction: Catheter-related blood stream infection (CRBSI), the most common complication of central vein catheter (CVC), was closely associated with high morbidity and mortality in hemodialysis (HD) patients. Conjunction with systemic antibiotic, antibiotic lock (ABL) is an important therapeutic option to salvage the catheter. With extra antimicrobial and biofilm removing properties, urokinase plasminogen activator (uPA)-based ABL could have a potential role in the treatment of CRBSI. Objective: In this study, we aimed to explore effectiveness of uPA-based (ABL) on microorganisms embedded in biofilms in vitro and CVC salvage rate in HD patients with CRBSI. Methods: In vitro, we induced biofilms formation on the surface of HD catheter by mimicking the development of CRBSI. Applying uPA with or without antibiotics on the kinds of microorganism biofilms to explore its antimicrobial and biofilm removing properties. In vivo, 86 HD patients diagnosed as CRBSI were retrospectively enrolled to see effectiveness of uPA-based ABL on catheter salvage rate as compare to heparin-based ABL. Results: uPA was effect to Staphylococcus epidermidis biofilms compared to Staphylococcus aureus, Escherichia coli, and Candida albicans. Less biofilm residues made the regrowth of S. epidermidis also limited. The combination of uPA with antibiotic showed better antimicrobial and antibiofilm activity than uPA alone or heparin-based ABL in vitro and in vivo. Among HD patients, uPA-based ABL did not cause any obvious adverse affects, and it was more effective in treating coagulase-negative Staphylococci related CRBSI than other microorganisms. Conclusions: The combination of uPA and a therapeutic plasma concentration of sensitive antibiotic can work together to effectively remove coagulase-negative S. epidermidis embedded in biofilms in vitro. uPA-based ABL is safe and effective therapeutic intervention for HD patients with CRBSI, especially compared to heparin-based ABL.

To investigate the correlation of different types of urinary abnormalities or different proteinuria and hematuria with the pathological injury of kidney in IgA nephropathy with isolated hematuria and/or mild proteinuria. Methods: Patients with primary IgA nephropathy, isolated hematuria and/or mild proteinuria were enrolled in the Department of Nephrology, the Second Xiangya Hospital, Central South University from January 2013 to January 2018. According to the difference of red blood cell count in urinary sediment and quantitative of 24-hour urinary protein (24 h-UP) during renal biopsy, the patients were grouped in 3 ways: a simple hematuria group, a hematuria and proteinuria group, and a simple proteinuria group; a proteinuria I group, a proteinuria II group, and a proteinuria III group; a hematuria I group, a hematuria II group, and a hematuria III group. The clinical parameters such as age, mean arterial pressure, blood urea nitrogen, serum creatinine, blood uric acid, 24 h-UP, and renal pathological damage were compared. Results: A total of 157 patients met the inclusion criteria, including 71 males and 86 females. The most common pathological type was focal and/or segmental glomerulosclerosis. The Lee's classification were dominated by grade III and IV, and the renal pathological injury was heavy. Immunoglobulin deposition was dominated by simple IgA deposition. The most common fluorescence intensity of IgA deposition was +++. 97 (61.78%) patients were accompanied by complement deposition and were mainly composed of simple complement C3 deposition. There were 18 patients (11.47%) in the simple hematuria group, 111 patients (70.70%) in the hematuria and proteinuria group, and 28 patients (17.83%) in the simple proteinuria group. Compared with the simple hematuria group, the proportion of patients with mild injury was lower in the simple proteinuria group, and the proportion of patients with moderate-to-severe injuries was increased (χ2=7.053, P=0.008). Compared with the hematuria and proteinuria group, the proportion of patients with mild injury was lower in the simple proteinuria group, and the proportion of patients with moderate-to-severe injury was increased (χ2=4.294, P=0.038). Compared with the proteinuria I group, the proportion of patients with mild injury was lower in the proteinuria III group, and the proportion of patients with moderate-to-severe injury was increased (χ2=5.433, P=0.020). There was no significant difference in the proportion of patients with renal pathological injury among different hematuria groups (P0.05). Conclusion: The clinical manifestations of patients with IgA nephropathy with hematuria and/or mild proteinuria are inconsistent with renal pathological damage. Some patients with mild clinical manifestations have severe renal pathological damage and the renal pathological damage is more serious in simple proteinuria. The more proteinuria, the heavier the renal pathological damage.目的：探讨单纯血尿和/或轻度蛋白尿IgA肾病患者的不同尿检异常类型、不同蛋白尿及血尿程度与肾脏病理的关系。方法：选择在中南大学湘雅二医院肾内科2013年1月至2018年1月经肾活检确诊的、临床表现为单纯血尿和/或轻度蛋白尿的原发性IgA肾病患者。根据肾活检时尿沉渣红细胞计数及24 h尿蛋白定量(quantitative of 24-hour urinary protein，24 h-UP)对所有患者进行3种方式的分组：单纯血尿组、血尿+蛋白尿组、单纯蛋白尿组；蛋白尿I，II，III组；血尿I，II，III组。比较各组患者的年龄、平均动脉压、血尿素氮、血肌酐、血尿酸、24 h-UP等临床指标以及肾脏病理损伤程度。结果：纳入157例患者，其中男71例，女86例。病理类型以局灶和/或节段硬化型最多见，Lee’s分级以III级和IV级为主，肾脏病理损伤较重。免疫球蛋白沉积以单纯IgA沉积为主，IgA沉积荧光强度以+++最多见，97例(61.78%)的患者伴有补体沉积，且以单纯补体C3沉积为主。单纯血尿组18例(11.47%)，血尿+蛋白尿组111例(70.70%)，单纯蛋白尿组28例(17.83%)。单纯蛋白尿组与单纯血尿组相比，轻度肾损伤患者比例降低，中重度肾损伤患者比例增高(χ2=7.053，P=0.008)；单纯蛋白尿组与血尿+蛋白尿组相比，轻度肾损伤患者比例降低，中重度肾损伤患者比例增高(χ2=4.294，P=0.038)；蛋白尿III组与蛋白尿I组相比，轻度肾损伤患者比例降低，中重度肾损伤患者比例增高(χ2=5.433，P=0.020)。不同血尿组肾脏病理损伤差异无统计学意义(P0.05)。结论：单纯血尿和/或轻度蛋白尿IgA肾病患者临床表现与肾脏病理损伤程度不一致。部分临床表现轻微的患者肾脏病理损伤较重，且以出现单纯蛋白尿时更明显；蛋白尿越多，肾脏病理损伤越重。.

The proteins BAFF, ST6GALNAC2, C1GALT1, and COSMC in peripheral blood mononuclear cells (PBMCs) and plasma levels of IgA1 and galactose-deficient IgA1 (Gd-IgA1) are potential biomarkers for IgAN nephropathy. In this study, we comparatively studied the changes of those biomarkers before and after tonsillectomy.Peripheral blood samples were obtained from 16 IgAN patients with pre- and post-tonsillectomy. IgAN was diagnosed based on results from analysis of percutaneous renal biopsy tissue. Peripheral blood samples from three patients without renal diseases (non-IgAN), before and after tonsillectomy, and 16 healthy controls were also examined. BAFF, ST6GALNAC2, C1GALT1, and COSMC mRNA levels in PBMCs were detected using real-time PCR. Plasma IgA1 content was measured by ELISA. Gd-IgA1 levels were determined using the VV lectin-ELISA method.BAFF, ST6GALNAC2, C1GALT1, and COSMC mRNA levels and the plasma concentrations of IgA1 and Gd-IgA1 in IgAN patients before tonsillectomy were significantly higher than those in healthy controls (P 0.05). Tonsillectomy significantly increased the expression of BAFF and ST6GALNAC2, and plasma IgA1 level, while it downregulated that of C1GALT1 and COSMC (P 0.05). However, in non-IgAN patients, tonsillectomy did not affect the mRNA levels of BAFF, ST6GALNAC2, C1GALT1, and COSMC, plasma IgA1 content and Gd-IgA1 level. Positive correlations were established between BAFF and IgA1 (r = 0.604, P 0.01) and between ST6GALNAC2 and Gd-IgA1 (r = 0.623, P 0.01).Tonsillectomy changes the mRNA levels of BAFF, ST6GALNAC2, C1GALT1, and COSMC in PBMCs, as well as the plasma IgA1 level in IgAN patients. BAFF and ST6GALNAC2 might regulate IgA1 secretion and O-glycosylation.

Background: Immunoglobulin (Ig) A nephropathy (IgAN) is the finding of immune deposits predominantly containing polymeric IgA in the glomerular mesangium on renal biopsy. Increasing evidence suggested that retinoic acid (RA) signaling selectively induces IgA isotype switching and basic leucine zipper transcription factor, ATF-like (BATF) controls the global regulators of class switch recombination (CSR) in lymphocytes. Great effort has been paid to identify whether impaired immune regulation along the ‘mucosa-bone marrow (BM) axis' play an important role in the pathogenesis of IgAN. Methods: The aim of the study was to investigate the expression of all-trans-RA (ATRA) and BATF, and to identify their impact on IgA CSR in IgAN patients and rat animal models. Blood samples and tonsillar tissue specimens were obtained from 22 patients with IgAN and 24 patients with chronic tonsillitis as control. Results: Immunohistochemical, RT-PCR and western blotting examination revealed that RA signaling and BATF productions are activated in IgAN patients compared with controls. Lipopolysaccharide and α-hemolytic streptococcus stimulation upregulated RA receptor (RAR) and BATF expression, promote IgA CSR and ATRA productions in tonsil mononuclear cells. RAR alpha (RARα) or BATF siRNA decreases IgA expression. We also built IgAN rat models and found that RARα, BATF and activation-induced cytidine deaminase were upregulated in the peripheral blood, spleen and BM. With ATRA (500 μg/kg body weight) treatment for 8 weeks, IgA deposition on glomeruli and mesangial cells proliferation increased. It also revealed that ATRA activated BATF and IgA CSR in vivo. Conclusion: These data point toward the role of RA signaling together with BATF in IgA CSR of IgAN, and the data also support the notion that mucosal immunization with neoantigen results in impaired mucosal and systemic IgA responses.

The relationship between tonsillar autoimmune response and the pathogenesis of IgA nephropathy (IgAN) has been previously demonstrated. However, the role of CD4 (+)CD25 (+)Treg cells, which play critical roles in maintaining peripheral tolerance and preventing autoimmunity, has not yet been defined in IgAN.Thirty-five patients with IgAN and 35 patients without renal disease were studied. The CD4 (+)CD25 (+)Treg cells were examined by flow cytometry. Clinical and laboratory data, such as serum creatinine and urinary samples, were obtained from each patient. Glomerular injury was assessed by histopathology. Serum IgA, C3, IL-2, IL-4 and IL-6 were analyzed by ELISA.CD4 (+)CD25 (+)Treg cells significantly decreased in IgAN patients compared with the controls before tonsillectomy (p0.05). CD4 (+)CD25 (+)Treg cells were negatively correlated with blood urea nitrogen, supernatant IL-4 and proteinuria in IgAN patients, and positively with estimated glomerular filtration rate. CD4 (+)CD25 (+)Treg cells gradually decreased as the severity of renal histology increased. In addition, serum IgA, IL-2, IL-6 and supernatant IL-4 elevated while CD4 (+)CD25 (+)Treg cells decreased in IgAN patients. CD4 (+)CD25 (+)Treg cells were significantly increased when serum IgA, IL-2, IL-6 and supernatant IL-4, urine protein and urine erythrocytes were decreased after tonsillectomy in patients with IgAN, but were still lower than those of the controls (p0.05).CD4 (+)CD25 (+)Treg cells were associated with IgAN, and tonsillectomy may increase CD4 (+)CD25 (+)Treg cells in IgAN patients, leading to clinical improvement.

Background IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis in the world. Hot pepper is the most favorite vegetable for Chinese in Hunan and Sichuan provinces. It can be assumed that capsaicin, the active ingredient of hot pepper, is a possible risk factor in diet in the pathogenesis of IgAN. Methods 22 subjects, including 11 IgAN patients and 11 non-IgAN patients were enrolled in this study. Tonsillar mononuclear cells were isolated and cultured for 3 days with or without capsaicin. Results In the absence and presence of capsaicin, the BAFF expression and IgA1 secretion were higher in IgAN patients than that in non-IgAN patients, meanwhile, the gene expression of C1GALT1 and Cosmc and IgA1 O-glycosylation level were significantly lower. In IgAN group, coincubated with capsaicin, IgA1 and BAFF secretion and BAFF expression by TMCs were significantly higher than that without capsaicin, furthermore, the level of mRNA encoding C1GALT1 and Cosmc and the level of IgA1 O-glycosylation were evidently lower. Conclusion Capsaicin may induce IgA1 secretion by activating BAFF expression, and bring to aberrantly IgA1 O-glycosylation by suppressing C1GALT1 and Cosmc expression. Therefore, to limit the consumption of hot pepper would be beneficial to patients with IgA nephropathy.

Background Clinical deterioration of IgA nephropathy (IgAN) is frequently preceded by episodes of upper respiratory tract infection such as tonsillitis. The aim of this study was attempt to investigate the expression and correlation of IL-4, IFN-γ and FcαRI in tonsillar mononuclear cells under stimulations of α-hemolytic streptococcus (HS) or lipopolysaccharide (LPS) in patients with IgA nephropathy. Methods Tonsillar mononuclear cells isolated from 26 patients with IgAN and 25 patients with chronic tonsillitis (CT) as controls were cultured for 72 h with or without α-hemolytic streptococcus (HS) and lipopolysaccharide (LPS) stimulation. Concentration of IL-4 and IFN-γ level were determined by ELISA. Expression levels of IL-4, IFN-γ and FcαRI mRNA were measured by real-time PCR, respectively. FcαRI expressing cells were tracked by flow cytometry. Results The supernatant concentration of IL-4, IFN-γ and the expression of IL-4, IFN-γ and FcαRI mRNA in the IgA nephropathy group was markedly increased compared with the non-IgAN group. With the stimulation of HS, the production of IL-4 and the FcαRI expressing cells in the IgA nephropathy group was significantly increased than the non-IgAN group, while the secretion of IFN-γ was remarkably decreased in the IgA nephropathy group than the non-IgAN group. Upon the LPS stimulation, the concentration of IL-4, IFN-γ in the supernatant of the IgA nephropathy group was markedly increased compared with the non-IgAN group. However, there wasn’t significant difference in the FcαRI expressing cells between the LPS stimulated IgAN group and the non-IgAN group. The expression of FcαRI is in a negative correlation with IL-4 while positive with IFN-γ. Conclusion The tonsillar mononuclear cells of IgAN may in a state of overactive immune response, which probably can promote the secretion of Th cytokines, involving in the pathogenesis of IgAN.

Background: Urgent-start dialysis is a major problem for incident dialysis population. Urgent start on hemodialysis is associated with an increased risk of infectious or mechanical complications, and its mortality is equal to or higher than that of urgent start on peritoneal dialysis (PD). However, compared to patients starting PD in a planned setting, those on urgent-started PD have an increased risk of mechanical complications and lower technique survival. Methods: In this study, 101 adult incident dialysis patients (≥18 years old) who underwent Tenckhoff catheter implantation were enrolled. All of the patients were grouped according to the urgent PD mode: the intermittent PD (IPD) or automatic PD (APD) group, and patients were followed for 1 year. The paired or independent t test was used to analyze the change of laboratory variables. Pearson chi-square test was applied to compare the short outcome between the 2 groups. Results: When PD was treated for 7 days and 1 month, the APD group has the lower serum potassium and phosphorus levels than the IPD group. The incidence of catheter dysfunction was significantly lower in the APD group. The morbidity of infection associated with PD in the first year was lower in the APD group despite no significant difference existing. The technique survival and patient survival rate have no evident difference between the 2 groups. Conclusion: Compared to IPD, urgent start on APD could reduce the risk of mechanical complication, which could be considered a gentle, safe, and feasible alternative to urgent start on IPD.

Background Mechanical catheter dysfunction caused by omentum entrapment remains a major complication of peritoneal dialysis (PD) therapy. The purpose of this study was to determine the outcomes of omentum folding at the time of primary open catheter insertion. Methods From March 2008 to December 2012, a total of 67 PD subjects were enrolled in the study and randomly assigned to receive either regular open insertion (ROI group, n = 33) or open insertion with omentum folding (OIOF group, n = 34). The primary outcome was defined as PD catheter tip migration with dysfunction. A systematic review was performed to analyze the outcomes of omentum management in PD catheter implantation, based on published data from 1990 to 2013. Results There was no statistical difference in baseline patient characteristics between the ROI and OIOF groups. Nine (27.3%) patients in the ROI group presented with catheter malposition in the late stage (>60 days) of the study, significantly more than in the OIOF group (two; 5.9%) (P = 0.049). Significant differences in catheter survival rate between the two groups were observed in the late stage (P = 0.030) and over the entire study period (P = 0.028). A higher incidence of irreversible catheter dysfunction was shown in the ROI group (15.2%), whereas none occurred in the OIOF group (P = 0.031). No statistical difference was determined in other catheter-related complications or patient survival rate. There were no statistical differences in peritoneal transport characteristics or dialysis adequacy between the two groups upon evaluation at 3, 6 and 12 months. Systemic review of current publications suggested that PD catheter placement with omentum management could lead to less irreversible catheter dysfunction and improved outcome of catheter survival. Conclusions Our data suggest that omentum folding at the initial time of open catheter placement can significantly reduce the risk of catheter tip migration with dysfunction and improve the outcome of the PD technique.

The purpose of the present study was to detect bacterial strains and antibiotic susceptibility in chronic tonsillitis patients with IgA nephropathy (IgAN) and without nephritis, in order to provide evidence for clinical therapy and pathogenesis of IgAN.A total of 53 patients with IgAN (group A) and 53 chronic tonsillitis patients without nephritis (group B) underwent tonsillectomy. The tonsil tissues of patients were collected under sterile condition. The bacteria in the tonsil crypt of patients in both groups were isolated and identified for antibiotic susceptibility test by the manual routine of the laboratory and also with the autoScan/Microscan system.There were bacteria in each specimen in both groups. The bacteria detection rate was 100%, but there was no significant difference between two groups (p 0.05). The 522 strains of bacteria in group A and 494 strains of bacteria in group B were isolated. Streptococcus. Neisseria, Hemophilus parainfluenzae. Staphylococcus. Bacillus proteus and Streptococcus pneumoniae were detected in both groups, but there was no significant difference in the types of bacteria between the two groups (all p 0.05). Alpha streptococcus was the most common in both groups. The antibiotic susceptibility test showed that there was no significant difference in the susceptibility to penicillin, chloramphenicol, macrolides, cephalosporin, gentamicin, amikacin sulphate, norfloxacin, ciprofloxacin, rifampicin and vancomycin between two groups (all p 0.05).Alpha streptococcus in both two groups can be detected and is the most common. There was no significant difference in bacterial strains and antibiotic susceptibility between two groups.

CD4+CD25+ T cells are critical for maintenance of immunologic self-tolerance. We measured the number of CD4+CD25+ cells in the patients with primary malignant hypertension related kidney injury, to explore the molecular pathogenesis of this disease. We selected 30 patients with primary malignant hypertension related kidney injury and 30 healthy volunteers. Information on clinical characteristics and laboratory tests was obtained from each subject. The number of CD4+CD25+ cells and glomerular injury were assessed by flow cytometry and histopathology, respectively. Both serum IL-2, IL-4, and IL-6 and endothelial cell markers were analyzed by ELISA. ADAMTS13 antibody was detected by Western blotting. CD4+CD25+ cells were significantly reduced in patients with primary malignant hypertension related kidney injury compared to controls (P +CD25+ cells was negatively related to blood urea nitrogen, serum uric acid, proteinuria, and supernatant IL-4; whereas positively associated with estimated glomerular filtration rate in patients. Gradually decreasing CD4+CD25+ cells were also found as increasing renal injury. Additionally, patients exhibited increasing supernatant IL-4, serum IL-2 and IL-6, endothelial cell markers, and anti-ADAMTS13 antibody compared with controls (all P +CD25+ cells may play a key role in the pathogenesis of primary malignant hypertension related kidney injury.

The efficacy of tonsillectomy in immunoglobulin A nephropathy (IgAN) remains controversial. The aim of the study was to conduct a randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgAN.We randomly selected 98 patients with biopsy-proven IgA nephropathy and randomly allocated to receive tonsillectomy combined with drug therapy (Group A) or drug therapy alone (Group B). The participating patients were entered into a 4-year single-center study. Remission and relapse rate were calculated for hematuria and proteinuria using the Kaplan-Meier method.No differences were found between the two groups in their baseline clinical and histological characteristics. Patients with tonsillectomy exhibited considerable improvement in the following aspects compared to those patients who did not undergo tonsillectomy: time to reach first remission (3.1 vs. 24.9 months, p 0.001) for hematuria and (2.5 vs. 26.1 months, p 0.001) for proteinuria, cumulative remission rate (91.8% vs. 46.9%, p 0.001 by log-rank test) for hematuria and (95.9% vs. 51.0%, p 0.001) for proteinuria, the duration of first remission (26.5 vs. 11.8 months, p = 0.0047) for hematuria and (23.5 vs. 10.5 months, p = 0.0012) for proteinuria, as well as lower relapse rate for hematuria and proteinuria in Group A.Our clinical data demonstrated that tonsillectomy could be beneficial for IgAN patients, particularly by contributing to faster and longer remission, as well as reducing the frequency of possible future relapses.

Background: Evidence regarding the optimal dose of tacrolimus (TAC) in treatment of idiopathic membra- nous nephropathy (IMN) remains inconclusive. The ob- jective of this study was to evaluate the efficacy and safety of low-dose TAC combined with prednisone for patients with IMN. Methods: We conducted a randomized prospective cohort study in IMN patients: 28 patients received oral TAC (target whole blood concentration of 2-4 ng/mL) plus prednisone for 12 months, and 28 patients re- ceived prednisone combined with intravenous cyclo- phosphamide (CYC) (750 mg/m 2 body surface) once every 4 weeks for 24 weeks. Results: Of the 56 patients who completed the 12-month treatment, complete remission (CR) occurred in 8 (28.6%) of the CYC group and 18 (64.3%) of the TAC group; partial remission (PR) occurred in 10 (35.7%) of the CYC group and 7 (25.0%) of the TAC group. The probability of remission (either CR or PR) was higher in the TAC group than in the CYC group (p = 0.0439, by log-rank test). Furthermore, a significantly greater improvement in proteinuria and serum albumin levels was observed in the TAC group compared with the CYC group. Patients treated with TAC can often show a rapid increase in their serum albumin levels before any obvious reduction of urinary protein excretion. Side ef- fects were mild and transitory in both groups. Conclusion: The results demonstrated that the com- bined therapy of low-dose TAC and prednisone is an effective and safe therapeutic method for Chinese adults with IMN. Low-dose TAC accompanied by pred- nisone is enough to induce remission in the majority of patients with IMN.

To explore the association of urinary podocyte excretion and renal expression of podocyte-specific marker podocalyxin (PCX) with clinicopathological changes in immunoglobulin A nephropathy (IgAN).Morning urine samples from IgAN patients and healthy controls were collected. The expression of glomerular PCX was quantified in 50 IgAN patients diagnosed by renal biopsy. IgAN was classified based on the Lee's Grading system and scored according to the Katafuchi semiquantitative criteria. Morphological evaluation of podocyte was determined by electron microscopy.The amount of urinary podocytes in the IgAN patients was significantly higher than that in the healthy controls (p0.01). Pairwise comparison among Lee's grades of IgAN showed that the median of urinary podocytes in Lee's I-II group was lower than that in Lee's III, IV, and V groups (p0.05); group III lower than group V (p0.05). The positive rate of urinary podocytes was the highest in Lee's IV and V groups (100%), and lowest in Lee's I-II group (55%). Multiple comparison among groups of Lee's grades of IgAN showed that the glomerular PCX expression in Lee's I-II group was higher than that in Lee's III, IV, and V groups (p0.05); groups III and IV higher than group V (p0.05). The amount of urinary podocytes in IgAN patients was negatively correlated with PCX expression (r = -0.702, p0.01), but positively correlated with 24-h urinary protein (r = 0.465, p0.01) and glomerular (r = 0.233, p0.01) and renal tubular pathological scores (r = 0.307, p0.05). The glomerular PCX expression was negatively correlated with 24-h urinary protein (r = -0.367, p0.05) and glomerular (r = -0.560, p0.05) and tubular pathological scores (r = -0.377, p0.05). Electron microscopy showed significant changes in podocytes of IgAN, especially in the foot process.The amount of urinary podocyte can reflect the loss of podocytes in renal tissue, which may be a marker of IgAN progression.

Background: Most nephrologists have believed that patients with isolated hematuria (IH) generally do not require treatment and have a good prognosis. The aim of this study was to analyze the pathological characteristics and emphasize the importance of renal biopsy for patients with IH. Methods: The pathological characteristics of 90 patients with IgA nephropathy confirmed by renal biopsy and presenting with IH were reviewed. We analyzed their pathological features according to the Oxford classification by using light and immunofluorescence. Results: Total samples included 68 females and 22 males. The age of onset with IH focuses on 20–30 years. At presentation, the focal and/or segmental glomerulosclerosis (FSGS) was the most frequent diagnosis (52.22%). The distribution of hematuria focused on 20–40 thousand. 46.67% of cases had global glomerulosclerosis which excluded the physical glomerular sclerosis, and the incidence of crescent formation was 24.44%. However, the proportion of glomerular sclerosis was mainly concentrated in less than 10%. Direct immunofluorescence showed simple IgA deposition was the most common (43.33%). 46.67% of patients had accompanying complement deposition, and 92.89% had complement 3 deposition. According to the Oxford classification, M1S₀E₀T₀ accounted for 53.33%. The incidence of M, S, E, and T was 100, 30, 14.44, and 22.22% respectively. 46.67% of patients included two or more pathological lesions. Conclusions: FSGS played an important role in patients with IgA nephropathy who presented with IH. For those patients, renal biopsy was a valuable diagnostic tool and should be offered in clinical settings to provide them with maximal potential benefits.

There are many reports suggesting a relationship between the tonsillar autoimmune response and the pathogenesis of IgA nephropathy (IgAN). Hyperproduction of IgA and IgA1 in tonsils could be caused by activation of the Ig class switching recombination (CSR). αGLT (germline transcripts) plays a critical role in the initiation of switching from Cμ to Cα, resulting in production of IgA. Activation-induced cytidine deaminase (AID) is a molecule essential for CSR and Ig gene conversion. The aim of this study was to investigate IgA and IgA1 levels in the supernatant of tonsillar mononuclear cells (TMCs) and the expression of Iα-Cα germline transcript and AID in TMCs stimulated with lipopolysaccharide or hemolytic streptococcus in IgAN patients and chronic tonsillitis patients.27 IgAN patients were admitted into our hospital from Jan. 2009 to Feb. 2010. Another 27 patients with chronic tonsillitis but without renal disease were selected as the control group. Tonsillar lymphocytes were isolated by density gradient centrifugation using Lymphocyte Separation Medium. The amount of IgA or IgA1 secreted in the culture supernatants was determined by specific enzyme-linked immunosorbent assay. Expressions of Iα-Cα germline transcript and AID mRNA were examined by reverse transcription real-time PCR. The AID protein was determined by Western blotting.The production of IgA and IgA1 protein, especially the ratio of IgA1/IgA in TMCs stimulated with or without 10 μg/ml of lipopolysaccharide or 1 × 10(8 )cfu/ml of hemolytic streptococcus, were significantly increased in the IgAN group compared with that in the non-IgAN group (P 0.05), and the IgA and IgA1 levels in TMCs stimulated with 10 μg/ml of lipopolysaccharide or 1 × 10(8 )cfu/ml of hemolytic streptococcus were markedly increased in patients with IgAN compared with the control group (P 0.05).The expressions of Iα-Cα and AID mRNA were significantly upregulated in TMCs stimulated with 10 μg/ml of lipopolysaccharide or 1 × 10(8 )cfu/ml of hemolytic streptococcus in patients with IgAN compared with control group (P 0.05). The expression of AID protein in TMCs stimulated with or without 10 μg/ml of lipopolysaccharide or 1 × 10(8 )cfu/ml of hemolytic streptococcus was significantly increased in the IgAN group compared with that in the non-IgAN group (P 0.05). The expression of AID protein in TMCs stimulated with 10 μg/ml of lipopolysaccharide or 1 × 10(8) cfu/ml of hemolytic streptococcus was significantly increased in patients with IgAN compared with the control group (P 0.05, P 0.01).Lipopolysaccharide or hemolytic streptococcus can induce the production of IgA and IgA1 and the expression of AID and Iα-Cα in TMCs from patients with IgAN. Our results indicate that the TMCs from patients with IgAN are capable of producing high levels of IgA and IgA1 when stimulated with lipopolysaccharide or hemolytic streptococcus, which may be due to the increased expression of AID and Iα-Cα.

The hallmark of IgA nephropathy (IgAN) is the mesangial deposits of polymeric IgA. However, the source of IgA1 and the mechanism of deposition of IgA1 in the mesangium remain unknown. To better understand its pathogenesis, we investigated the expression of CD19(+)CD5(+)B cells and IgA1-positive cells in the tonsils of IgAN patients. Immunofluorescence was used to visualize the locations of CD19(+)CD5(+)B cells and IgA1-positive cells in the tonsils. In this study, it was demonstrated that CD19(+)CD5(+)B cells are usually found in germinal centers and in the capsule covering the upper parts of the nodules of lymphoid tissue (cap of the nodule). The expression of IgA1-positive cells in tonsil tissue can be seen in the cap of the nodule and subepithelial tissue. There is a significant relationship between IgA1 and CD19(+)CD5(+)B cells. The level of CD19(+)CD5(+)B cells is positively correlated to the severity of renal pathological changes. These findings suggest that CD19(+)CD5(+)B cells in the tonsils could have an impact on the pathogenesis of IgAN.

SUMMARY: Aim: The aim of the present report was to investigate the probable association of circulating levels of PAI-1 and expression of PAI-1 in internal iliac artery walls with atherosclerotic disease in chronic haemodialysis (HD) patients. Methods: Sixty-eight non-diabetic HD patients and 50 age- and sex-matched healthy normotensive controls participated in the study. Atherosclerotic disease in both groups was assessed by measuring intima-media thickness (IMT) and plaque score of the common carotid arteries using an ultrasound scanner. Levels of serum PAI-1, C-reactive protein (CRP), interleukin (IL)-6 and lipids profile were measured. Internal iliac artery samples were obtained at the time of renal transplantation. Quantitative expression of PAI-1 in internal iliac artery walls was assessed by positive unit (pu) value using an immunohistochemical method. In addition, the IMT and carotid plaque score were analyzed in relation to circulating levels of PAI-1 and expression of PAI-1 in internal iliac artery walls. Results: Compared with control subjects, HD patients had significantly increased common carotid artery (CCA)-IMT (P = 0.002). Atherosclerotic plaques were detected in 42 (61.76%) of HD patients and in two (4%) controls. The above ultrasonographic indices were correlated with age in HD patients (P

The dialysis population has grown rapidly in recent decades. Despite the high cost and poor outcomes of dialysis treatment for ESRD, there are scant data about the level of renal function and the relationship of renal function and serum albumin at the start of dialysis in Chinese ESRD patients.We report the level of serum creatinine (Scr), glomerular filtration rate (GFR), and serum albumin (Salb) in 514 ESRD in-patients who began their dialysis treatment between January 2001 through December 2007 at two large dialysis centers in Changsha, Hunan, China. Data were obtained through reviewing the case records of all 514 patients. GFR was predicted by an equation developed from the Modification of Diet in Renal Disease Study. In addition, serum albumin was analyzed in relation to levels of predicted GFR.The mean (SD) and median predialysis serum creatinine was 1121.92 +/- 458.24 and 1032 micromol/L. The mean (SD) and median predicted GFR was 4.98 +/- 2.24 and 4.47mL/min/1.73m(2). The proportion of patients with predicted GFR of10, 5 to 10, and5 mL/min/1.73m(2) was 3.7, 36.2, and 60.1%, respectively. The mean predicted GFR was significantly lower among younger patients, uninsured patients, unemployed or farmer patients, patients who were employed, students, patients who selected hemodialysis, patients with ESRD caused by diseases other than diabetes, patients with BUN above the mean, and patients with hemoglobulin beneath the mean. Compared with patients who started with GFR5mL/min, the patients who started with GFRor=5mL/min had significantly higher plasma urea and creatinine levels but significantly lower creatinine clearance (mL/min per 1.73m(2)) and parameters of nutritional status, such as serum albumin, body weight, and BMI.A wide variation existed in renal function at the initiation of dialysis in partial Chinese ESRD patients. Most patients start dialysis at very low levels of predicted GFR. The nutritional status in patients who start dialysis early was better than those in patients who start dialysis when GFRor= 5mL/min. Further studies are needed to analyze the impact of level of renal function and nutritional status at the start of dialysis on the outcomes of ESRD.

This study aimed to evaluate the extent of apoptosis of tonsillar mononuclear cells (TMCs) derived from patients with IgA nephropathy (IgAN) and the effects of triptolide (TP) on the apoptosis of these TMCs.TMCs were isolated from tonsillar tissues of patients with IgAN or chronic tonsillitis (control group). Rates of TMCs apoptosis were measured by annexin V-fluorescein isocyanate (FITC)/propidium iodide (PI)-labeled flow cytometry (FCM). Expression levels of Bcl-2 family proteins were quantified by immunohistochemistry of fixed tonsillar sections and Western blot analyzes of TMCs lysates. TMCs from IgAN patients were treated 10, 20, or 30 ng/mL TP for 24 h and then evaluated for viability by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, for the percentage of apoptotic cells by FCM, and for the relative expression levels of Bcl-2 family proteins by Western blot analysis.Compared to TMCs from the control group, TMCs from the IgAN group demonstrated lower rates of apoptosis, higher expression levels of the anti-apoptosis proteins Bcl-2 and Bcl-xL, and lower expression levels of the pro-apoptosis protein Bax. Treatment of IgAN patient-derived TMCs with 10, 20, or 30 ng/mL TP for 24 h suppressed the viability and promoted the apoptosis of TMCs in a dose-dependent manner. Western blot analysis revealed a TP dose-dependent decrease in Bcl-2 and Bcl-xL expression levels, in parallel with increased Bax protein levels.TMCs from IgAN patients may be in a state of inhibited apoptosis mediated by Bcl-2 family proteins, which may be reversed by TP treatment.

Background: Immunoglobulin class-switch recombination (CSR) is crucial for the expression of IgA, and it plays a vital role in the physiopathology of IgA nephropathy (IgAN). The aim of the study is to investigate the effect of polyriboinosinic:polyribocytidylic acid (poly(I:C)) in modulating toll-like receptor (TLR) 3-B-cell-activating factor belonging to the TNF family (BAFF) axis activation, which in turn promotes IgA CSR of IgAN patients and the IgAN rat model. Methods: Blood samples and tonsillar tissue specimens were obtained from 24 patients with IgAN and 26 patients with chronic tonsillitis as control. We also used the IgAN rat model to investigate the relationship between viral infection and IgA CSR. Results: Immunohistochemical and ELISA western blotting examination revealed that the TLR3/BAFF axis is activated in IgAN patients when compared to controls. Synthetic double-stranded RNA poly(I:C) stimulation upregulates the TACI/TLR3/TRIF/TRAF6 expression and promotes IgA CSR and BAFF productions in tonsil mononuclear cells. TLR3 or BAFF siRNA decreases IgA expression. In IgAN rat models, TLR3/BAFF signaling was highly activated. With 200 μg poly(I:C) sodium salt into the left naris for 8 weeks, IgA was highly deposited on glomeruli. It also revealed that poly(I:C) activated TLR3/BAFF axis and IgA CSR in vivo. Conclusion: These data points toward the role of TLR3/BAFF axis in IgA CSR of IgAN, and the data also support the notion that mucosal immunization with virus infection results in impaired mucosal and systemic IgA responses.

CD4+CD25+ cells are critical regulators in almost all of the animal models of human organ-specific autoimmune diseases, transplant rejection and allergic diseases. We aimed to explore the role of CD4+CD25+ cells in the pathogenesis of multiple myeloma (MM) related renal impairment (RI). Thirty patients with MM related RI and 30 healthy volunteers were studied. The number of CD4+CD25+ cells was examined by flow cytometry. Clinical and laboratory data were collected from each subject. Glomerular injury was assessed by histopathology. Serum IL-2, IL-4 and IL-6 were analyzed by ELISA. CD4+CD25+ cells significantly decreased in MM related RI patients compared to the controls (P+CD25+ cell number was negatively associated with blood urea nitrogen (BUN), supernatant IL-4, serum IL-6, monoclonal immunoglobulin and β2-microglobulin, as well as bone marrow plasma cell percentage and proteinuria; whereas positively associated with estimated glomerular filtration rate (eGFR) (all P +CD25+ cells gradually decreased as the Clinic Stage increased. The number of CD4+CD25+ cells reduced in MM related RI patients and was correlated with disease severity. CD4+CD25+ cells may play an important role in the pathogenesis of MM related RI.

Background: Gentamicin-induced nephrotoxicity is one of the most common causes of acute kidney injury (AKI). The phenotypic alterations that contribute to acute kidney injury include inflammatory response and oxidative stress. Curcumin has a wide range biological functions, especially as an antioxidant. This study was designed to evaluate the renoprotective effects of curcumin treatment in gentamicin-induced AKI. Methods: Gentamicin-induced AKI was established in female Sprague–Dawley rats. Rats were treated with curcumin (100 mg/kg body mass) by intragastric administration, once daily, followed with an intraperitoneal injection of gentamicin sulfate solution at a dose of 80 mg/kg body mass for 8 consecutive days. At days 3 and 8, the rats were sacrificed, and the kidneys and blood samples were collected for further analysis. Results: The animals treated with gentamicin showed marked deterioration of renal function, together with higher levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) in the plasma as compared with the controls. Animals that underwent intermittent treatment with curcumin exhibited significant improvements in renal functional parameters. We also observed that treatment with curcumin significantly attenuated renal tubular damage, apoptosis, and oxidative stress. Curcumin treatment exerted anti-apoptosis and anti-oxidative effects by up-regulating Nrf2/HO-1 and Sirt1 expression. Conclusions: Our data clearly demonstrate that curcumin protects kidney from gentamicin-induced AKI via the amelioration of oxidative stress and apoptosis of renal tubular cells, thus providing hope for the amelioration of gentamicin-induced nephrotoxicity.

Background Tubulointerstitial damage (TID) is an important mediator in the progression of chronic proteinuric nephropathies. Our aim in this study was to evaluate the relationship between several clinical predictors and TID in adult-onset primary nephrotic syndrome in China. Methods One hundred ninety-five adult inpatients who were diagnosed with primary nephrotic syndrome based on clinical presentation and biopsy results were enrolled in this study from March 2003 to September 2005. The degree of TID was graded by a semiquantitative method including Results In all patients, the rate of glomerulosclerosis was correlated with the severity of TID. Serum creatinine and uric acid ( r = 0.183, p = 0.012 and r = 0.377, p = 0.00001, respectively) but not serum lipid or total 24-h urinary protein were related with TID. In 64 patients, urinary excretion of IgG ( r = 0.443, p = 0.00001) but not of albumin, transferrin, retinal-binding protein, or α1-microglobulin were significantly associated with the extent of TID. Proteinuria selectivity index based upon IgG also correlated significantly with the extent of TID ( p = 0.0001) (score 0–1 vs. score ≥2). Conclusions These results showed that serum creatinine and uric acid, the excretion of urinary IgG and proteinuria selectivity index based upon IgG, were highly correlated with the severity of TID in adult-onset primary nephrotic syndrome. These clinical parameters might be useful for predicting the development and progression of proteinuric nephropathy as independent risk factors.

Acute tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease usually having a good prognosis. But the recurrence of uveitis and the chronic progression of kidney injury are still main problems. We report a 15-year-old girl with TINU who showed proteinuria, pathological renal change, multiple organ dysfunction, and immune disorders. After 2 months of 1 mg/kg/day corticosteroid therapy, 24-h urine protein, liver function tests, and creatine kinase returned to normal level. In spite of this, steroid was tapered off slowly and small dose of steroid maintenance therapy lasted for 1 year. Her kidney and ocular symptoms did not recur during 5 years of follow-up. We suggest low-dose steroid maintenance therapy to decrease the recurrence of the TINU syndrome.

A 28-year-old female suffered from nephrotic syndrome after a long-term use of mercury-containing, skin-lightening cream. The blood and urinary mercury content of this patient increased with use. Renal biopsy showed minimal change disease. Her symptoms were relieved 6 months after discontinuing use of the cream and receiving sodium dimercaptosulfonate and glucocorticosteroid treatments. Proteinuria disappeared, and blood and urinary mercury levels returned to normal. Previous reports of nephrotic syndrome caused by mercury-containing, skin-lightening creams have mostly been identified as be.ing due to membranous nephropathy. Minimal change disease has been reported in a few case reports published in the English language. Here we report a case of nephrotic syndrome with minimal change disease following exposure to a mercury-containing, skin-lightening cream. We also reviewed relevant published reports to summarize clinical features and treatments and to explore the possible mechanisms involved.

Many studies found that hemoglobin (Hb) fluctuation was closely related to the prognosis of the maintenance hemodialysis patients. We investigated the association of factors relating dialysis dose and dialyzer membrane with Hb levels. We undertook a randomized clinical trial in 140 patients undergoing thrice-weekly dialysis and assigned patients randomly to a standard or high dose of dialysis; Hb level was measured every month for 12 months. In the standard-dose group, the mean (±SD) urea reduction ratio was 65.1% ± 7.3%, the single-pool Kt/V was 1.26 ± 0.11, and the equilibrated Kt/V was 1.05 ± 0.09; in the high-dose group, the values were 73.5% ± 8.7%, 1.68 ± 0.15, and 1.47 ± 0.11, respectively. The standard deviation (SD) and residual SD (liner regression of Hb) values of Hb were significantly higher in the standard-dose group and low-flux group. The percentage achievement of target Hb in the high-dose dialysis group and high-flux dialyzer group was significantly higher than the standard-dose group and low-flux group, respectively. Patients undergoing hemodialysis thrice weekly appear to have benefit from a higher dialysis dose than that recommended by current KDQQI (Kidney Disease Qutcome Quality Initiative) guidelines or from the use of a high-flux membrane, which is in favor of maintaining stable Hb levels.

CD(+)(4)CD(+)(25) Treg cells are of critical importance for maintenance of tolerance. The purpose of the this study was to observe the number of CD(+)(4)CD(+)(25) Treg cells in the patients with thrombotic thrombocytopenic purpura (TTP) associated with systemic lupus erythematosus (SLE), and to study pathogenesis of TTP with SLE.Seven patients with TTP associated with SLE and seven healthy volunteers were studied. The CD(+)(4)CD(+)(25) Treg cells were examined by flow cytometry. Clinical and laboratory data, such as urinary protein, serum creatinine, endothelial markers and immunologic serologics, were obtained from each patient and healthy volunteer. Glomerular injury was assessed by histopathology. Serum IL-2, IL-4, IL-6 and anti-endothelial cell antibody were analyzed by ELISA and anti-ADAMTS13 antibody were detected by Western blotting.CD(+)(4)CD(+)(25) Treg cells significantly decreased in TTP with SLE patients compared with controls (p 0.05). CD(+)(4)CD(+)(25) Treg cells are negatively correlated with blood urea nitrogen, serum uric acid, supernatant IL-4, and proteinuria, and positively with estimated glomerular filtration rate (eGFR) in TTP with SLE patients. [Formula: see text] Treg cells gradually decreased as the severity of renal histology increased. Serum IL-2, IL-6, supernatant IL-4, anti-endothelial cell antibody, and anti-ADAMTS13 antibody significantly increased in TTP with SLE patients compared to those of the control groups (all p 0.05). In contrast, serum levels of C3 were significantly decreased in TTP with SLE patients compared to those of the control groups (p 0.05).CD(+)(4)CD(+)(25) Treg cells are not only lower in TTP with SLE patients, but also are correlated with disease severity in TTP with SLE patients.CD(+)(4)CD(+)(25)Treg cells may play an important role in the pathogenesis of TTP with SLE.

Objective The intent of this study was to evaluate the clinical outcome and risk factors affecting mortality of the continuous ambulatory peritoneal dialysis (CAPD) patients in a single peritoneal dialysis (PD) center over a period of 10 years. Patients and methods We retrospectively analyzed patients on PD from June 2001 to June 2011. The clinical and biochemical data were collected from the medical records. Clinical variables included gender, age at the start of PD, smoking status, body mass index (BMI), cause of end-stage renal disease (ESRD), presence of diabetes mellitus and blood pressure. Biochemical variables included hemoglobin, urine volume, residual renal function (RRF), serum albumin, blood urea nitrogen (BUN), creatinine, total cholesterol, triglyceride, comorbidities, and outcomes. Survival curves were made by the Kaplan-Meier method. Univariate and multivariate analyses to identify mortality risk factors were performed using the Cox proportional hazard regression model. Results A total of 421 patients were enrolled, 269 of whom were male (63.9%). The mean age at the start of PD was 57.9 ± 14.8 years. Chronic glomerulonephritis was the most common cause of ESRD (39.4%). Estimation of patient survival by Kaplan-Meier was 92.5%, 80.2%, 74.4%, and 55.7% at 1, 3, 5, and 10 years, respectively. Patient survival was associated with age (hazard ratio [HR]: 1.641 [1.027 – 2.622], p = 0.038), cardiovascular disease (HR: 1.731 [1.08 – 2.774], p = 0.023), hypertriglyceridemia (HR: 1.782 [1.11 – 2.858], p = 0.017) in the Cox proportional hazards model analysis. Estimation of technique survival by Kaplan-Meier was 86.7%, 68.8%, 55.7%, and 37.4% at 1, 3, 5, and 10 years, respectively. In the Cox proportional hazards model analysis, age (HR: 1.672 [1.176 – 2.377], p = 0.004) and hypertriglyceridemia (HR: 1.511 [1.050 – 2.174], p = 0.026) predicted technique failure. Conclusion The PD patients in our center exhibited comparable or even superior patient survival and technical survival rates, compared with reports from other centers in China and other countries.

Purpose: To evaluate the nephrotoxicity of high- and low-osmolar contrast media (HOCM, LOCM) on kidneys in Sprague-Dawley rats. The protective role of amlodipine was studied. Material and Methods: Forty rats of both sexes were randomly divided into 5 groups (n = 8/group) and glycerine for inducing renal failure was given to all rats except controls. Results: In diatrizoate-injected rats, blood urea nitrogen (BUN) and serum creatinine (SCr) were increased; levels of phospholipase A2 (PLA2), lipid peroxide (LPO) and calcium were also increased in renal tissues. There was no significant difference between LOCM (iohexol) animals and glycerol controls either in the renal levels of PLA2, LPO and calcium or in the levels of BUN and SCr. The histologic changes were milder in the LOCM animals than in the HOCM animals. In the group pretreated with amlodipine, no increase in the levels of BUN or SCr was discovered and the renal content of PLA2, LPO and calcium were significantly lower than in the HOCM group; the renal injuries induced by diatrizoate were alleviated. Conclusion: The HOCM, diatrizoate, was more toxic to rat kidneys than the LOCM iohexol; PLA2, LPO and calcium load played a role in producing renal function impairment induced by diatrizoate meglumine; amlodipine protected the renal tissue from nephrotoxicity induced by diatrizoate.

Background/Aim: Clinical development and exacerbation of IgA nephropathy (IgAN) are frequently preceded by episodes of upper respiratory tract infection such as tonsillitis. This study aimed to determine the role of the interleukin-4 (IL-4)/signal transducer and activator of transcription 6 (STAT6) signaling pathway and homeodomain-interacting protein kinase 2 (HIPK2) in aberrant IgA1 O-glycosylation production, and identify potential therapeutic targets in IgAN. Methods: Expression levels of IL-4, STAT6, core1β1,3-galactosyltransferase (C1GALT1C1), core1β3GalT-specific molecular chaperone (Cosmc) and HIPK2 in tonsil components were examined by immunohistochemical and immunofluorescence staining. Lymphocytes isolated from 22 patients with IgAN and 24 patients with chronic tonsillitis (CT) as controls were cultured for 72 h with or without IL-4, lipopolysaccharide (LPS) and α-hemolytic streptococcus (HS) stimulation. Expression levels of STAT6, C1GALT1C1, Cosmc, HIPK2-mRNA and protein were measured by real-time PCR and Western blot analysis, respectively. The concentration of IgA1 and level of O-glycosylation were determined by ELISA and Vicia villosa (VV) lectin-binding assay. To determine the contribution of HIPK2 in IgA secretion and O-glycosylation, cells were subjected to experiments for evaluation of HIPK2 silencing by Hipk2-siRNA transfection. Results: The IL-4/STAT6 signaling pathway was highly activated in all tonsil tissues (including the germinal center and tonsillar crypt epithelium) of IgAN patients, but the gene or protein expression of β1,3-Gal transferase (C1GALT1) and COSMC decreased significantly in patients with IgAN in comparison with those with CT. Hipk2 production in the tonsils derived from IgAN patients was significantly higher than that of CT patients. HIPK2-mRNA expression significantly negatively correlated with renal function as expressed by the estimated glomerular filtration rate, and also significantly positively correlated with daily proteinuria. The level of IL-4, STAT6 and HIPK2 were closely related with Lee's pathological grading system. The levels of mRNA and protein encoding STAT6 and Hipk2 in cells coincubated with IL-4, LPS and HS were significantly higher than those in the controls without stimulation; however, in the IgAN group the levels of mRNA and protein encoding C1GALT1 and Cosmc were significantly lower compared to the controls. IgA1 concentrations of supernatants in IgAN patients were remarkably higher under conditions of external stimulation. As expected, the optical density value of VV lectin binding to IgA1 increased after external stimulation in the IgAN group. By siRNA transfection, our results clearly indicate that Hipk2 negatively regulates C1GALT1 and Cosmc expression. Importantly, HIPK2-siRNA attenuates the aberrant glycosylation of IgA1 secretion. Conclusion: We identified and confirmed that activation of the IL-4/STAT6 signaling pathway has a crucial role in aberrant glycosylation of IgA1 secretion. HIPK2, a protein kinase previously unrecognized in kidney disease, may mediate the glycosylation of IgA1. We believe that HIPK2 could be a new therapeutic target for IgAN, especially as protein kinases are ‘drugable' targets.

We observed serum parameters and urinary findings of IgA nephropathy (IgAN) patients in the short and longer time after tonsillectomy, to provide evidences to clarify the role of tonsils in the pathogenesis of IgAN and the feasibility of tonsillectomy for IgAN patients.For the short-term study, 19 patients with both IgAN and chronic tonsillitis (group A) and 19 patients with chronic tonsillitis (group B) were performed bilateral tonsillectomy and 19 healthy people as normal controls (group C). Another 115 patients with IgAN and chronic tonsillitis including 61 patients for tonsillectomy combined with drug therapy and 54 for drug therapy alone followed up for 12 months.Fourteen patients of group A showed a deterioration of urinary findings, while only 2 patients of group B showed deterioration (P0.01). Both serum IgA and IgA1 levels were significantly higher in group A than that in group B or group C (P0.05, respectively). Levels of serum IgA and IgA1 of group A increased after tonsillectomy and did not increase instantly, but increased at day 3, then decreased at day 5. Both serum IgA and IgA1 levels were positively related to urinary red blood cell count (P0.01, r s = 0.362, r s = 0.347, respectively). For longer-term study, urinary findings of IgAN patients underwent tonsillectomy were improved significantly than that of patients without tonsillectomy (P0.05).Tonsils play an important role in the development of IgAN, and tonsillectomy may be a feasible treatment method for IgAN patients with chronic tonsillitis.

To investigate the effect of plasminogen activator inhibitor-1 (PAI-1), tissue type plasminogen activator (t-PA), and endothelin-1 (ET-1) on the atherosclerosis progress in the maintenance hemodialysis patients.We enrolled 19 patients with maintenance hemodialysis (MHD) and 11 healthy people as control. Patients were divided into 2 groups according to their age above or below 40 years old (11 and 8 in each, respectively), whereas the subjects in control group were below 40 years old. All the clinical information of the research subjects was collected: including age, gender, time of hemodialysis, blood pressure, blood urea nitrogen (BUN), and serum creatinine (SCr). Immunohistochemistry and pathological image analysis were used to investigate the pathological changes, calcification and the expression of PAI-1, t-PA, and ET-1 on the blood vessel.Compared with the age-matched healthy control group, there were higher blood vascular media thickness, blood vascular media thickness/diagmeter ratio, blood vascular media thickness area/vascular inter-wall area ratio (P0.05) and more calcification (P0.05) in the the internal iliac artery in the chronic renal failure MHD patients. All the results were similar when compared the above 40 years old group with the below 40 years old one in the chronic renal failure MHD patients. There were positive correlation of blood vascular media thickness with age and blood pressure (P0.05). Expression of PAI-1, ET-1, t-PA on the internal iliac artery vessel was elevated in the chronic renal failure MHD patients compared with the health control (P0.05). The level of PAI-1 or ET-1 was much higher in the above 40 years old group than the below 40 years old one in the chronic renal failure MHD patients, whereas there was no significant difference in the t-PA expression between the 2 groups (P0.05). There were positive correlation of PAI-1 or ET-1 expression with age and blood pressure (P0.05). There were positive correlation of PAI-1 or ET-1 expression with blood vascular media thickness and calcification (P0.05 or P0.01). There was no correlation of hemodialysis time with blood vascular media thickness, calcification, PAI-1, t-PA, or ET-1 expressions.MHD patients accompany with atherosclerosis which is severer in the patients above 40 years old than the patients below 40 years old. The higher of the blood pressure, the severer of the atherosclerosis. Abnormal expression of PAI-1 plays an important role in the progress of the atherosclerosis in the chronic renal failure MHD patients, whereas t-PA has no function in this process. The level of PAI-1 and ET-1 would be helpful to evaluating the degree of atherosclerosis in the chronic renal failure MHD patients. Hemodialysis time may not be a potential accelerator for atherosclerosis progression.

To explore the changes and clinical significance of saliva urea, creatinine (Cr), uric acid (UA) in both healthy people and chronic kidney disease (CKD) patients, and to provide a noninvasive, quick, accurate and reliable test to diagnose kindey disease.Urea, Cr and UA in the saliva and serum collected from both healthy people and the CKD patients were measured by biochemical analyzer. We calculated the correlation coefficient of Urea, Cr and UA between the saliva and serum, compared the levels of saliva Urea, Cr and UA among CKD patients in different periods, drew the receiver operation characteristic (ROC) curve and analyzed the sensitivity and specificity of saliva Urea, Cr and UA to predict CKD patients in various periods.The concentrations of Urea, Cr and UA in both the saliva and the serum were positively correlated in healthy individuals and CKD patients (r = 0.918, 0.932, 0.840 and 0.984, 0.971, 0.920). The levels of saliva Urea, Cr and UA in the CKD patients were significantly higher than those of healthy people (P0.05). Saliva Urea, Cr and UA concentrations of middle and late stage CKD patients were obviously higher than those of healthy people and early stage CKD patients (P0.05). Areas under the curve (AUC) of the ROC of Urea, Cr and UA to diagnose diverse periods of CKD were 0.898, 0.897 and 0.848. The sensitivity was 0.806, 0.776 and 0.704; and the specificity was 0.968, 0.989 and 0.871.The levels of Urea, Cr and UA between the saliva and the serum are closely related. The concentration of saliva Urea, Cr and UA can reflect the renal damage, monitor kidney function of the CKD patients, and help diagnose middle to late stage CKD patients. It is a simple, nonivasive and quick method.

To investigate the effect of different intravenous iron treatment regimens on anemia and oxidative stress in maintenance hemodialysis (MHD) patients.A total of 58 MHD patients were randomly divided into a multi-frequency low-dose intravenous iron group (iron sucrose 25 mg, twice a week for 8 weeks, n=19), a less-frequency regular-dose intravenous iron group (iron sucrose 100 mg, once every two weeks for 8 weeks, n=19), and a non-iron group (n=20). Another 20 healthy people served as a control group (n=20). The changes of hemoglobin (Hb), hematocrit (HCT), serum ferritin (SF) and transferrin saturation (TSAT), as well as the oxidative stress parameters of malon-dialdehyde (MDA), superoxide dismutase (SOD) and myeloperoxidase (MPO) were detected before and after the treatment.After 8 weeks, compared with the non-iron group, the levels of Hb, HCT, SF and TSAT in the two iron groups were significantly elevated (P0.01), but there was no difference between the two iron groups (P0.05). After the single dialysis, the two iron groups had higher level of serum MDA, MPO and lower level of serum SOD than that of the non-iron supplementation group (P0.01). The multi-frequency low-dose intravenous iron group had lower level of serum MDA [(5.37 ± 0.73) nmol/mL vs (6.37±1.67) nmol/mL], MPO [(81.41±7.60) U/L vs (96.75±16.97) U/L] and higher level of serum SOD [(84.77 ± 14.02) U/mL vs (68.23 ± 4.90) U/mL] than that of the less-frequency regular-dose intravenous iron group. After 8 weeks, there was no significant difference between the two iron groups (P0.05).Multi-frequency low-dose intravenous iron can effectively improve anemia in MHD patients, whose acute oxidative stress is lower than that of less-frequency regular-dose intravenous iron, and is a relatively safe and effective intravenous iron treatment regimen.

To investigate the new pathological classification of diabetic nephropathy (DN) published by Research Committee of the Renal Pathology Society in 2010.Renal biopsy specimens were obtained from 37 patients with type 2 diabetes mellitus with micro-albuminuria (MAU) or clinical albuminuria (CAU). These samples were classified according to new pathological classification for DN and new standard scores for interstitial vascular injury.Before the classification, DN was seen in 26 palients. After re-analysis according to the new pathological classification, the patients diagnosed with DN increased to 32. In these 32 DN patients, 1 was classified as type I, 3 as type IIa, 2 as type IIb, 23 as type III and 3 as type IV; 12 patients had mild interstitial injury, 15 had midrange interstitial injury, while 5 had severe interstitial injury.The new pathological classification of DN can increase the diagnosis rate and attract more attention to tubular and interstitial damage in DN, contributing to the early diagnosis and treatment of DN.

This study was planned to summarize the clinical and pathological features of renal amyloidosis in order to improve its early and accurate diagnosis.The clinical and pathological data were analyzed from 28 patients with renal amyloidosis in the Second Xiangya Hospital from January 2005 to September 2010.Twenty seven out of the 28 (96.4%) cases were over 40 years old and presented with nephrotic syndrome. The initial diagnosis of 23 patients (82.1%) was not renal amyloidosis at their first visit to the local hospital. The pathophysiological finding included diffused deposition of amorphic and eosinophilic amyloid substance in glomerular mesangial, capillary membrane loop, interstitial, vascular, and tubular wall. 26 cases were attributed to the AL type and 2 cases to AA type. 25 patients (89.3%) were found to have monoclonal light chain in serum or urine by protein electrophoresis.Renal amyloidosis is frequently neglected by local physicians in China. Renal amyloidosis should be highly suspected if the middle-aged nephrotic patient was accompanied by weight loss, organ enlargement, and monoclonal light chains in serum or urine. Renal biopsy, especially with examination under the electron microscopy, is the key to the early diagnosis of renal amyloidosis. Potassium permanganate staining and immunofluorescence examination could help to distinguish primary from secondary amyloidosis.

This study aimed to investigate the immunological relationship and the mechanism between tonsillar inflammation and immunoglobulin A nephropathy (IgAN). Tonsillar mononuclear cells (TMCs) were prepared from 13 patients with IgAN and 13 patients with chronic tonsillitis but without renal disease. The human renal tubular epithelial cell (TEC) line, HK-2, was used to test the effects of secretions from the TMCs. Phytohemagglutinin (PHA) was used to induce the inflammatory responses in TMCs. The secretions from TMCs, stimulated with or without PHA, were collected and applied to HK-2 cells. The proliferation, apoptosis, and epithelial–mesenchymal transition (EMT) of HK-2 cells were evaluated. The expression of key components during apoptosis and EMT was measured. The secretions from PHA-stimulated IgAN TMCs significantly inhibited proliferation, promoted apoptosis, and down-regulated Bcl-2 in HK-2 cells (P

To study correlation between urinary retinol binding protein (RBP) content and renal tubular damage.A total of 1 353 healthy people and 186 patients with renal tubular damage diagnosed by renal biopsy were enrolled. The indicators such as endogenous creatinine clearance rate (Ccr), creatinine(Cr), urinary retinol binding protein(RBP), urinary β(2)-microglobulin(β(2)-MG), urinary N-acety1-beta-D-glucosaminidase (NAG), urine specific gravity(SG), urine osmolality of the 2 groups were examined and compared. Score of tubulointerstitial impairing and all indicators were analyzed by Spearman rank correlation analysis, and the sensitivity and specificity of indicators were calculated.Renal tubular damage was positively correlated with urinary RBP, β2-MG, NAG (r=0.863, P0.001; r=0.777, P0.001; r=0.374, P=0.002, respectively), while negatively correlated with urine osmolaling, SG (r=-0.519, P0.001; r=-0.624, P0.001, respectively). The specificity and sensitivity for renal tubular damage of RBP were 91.03% and 72.06%.RBP is an idea marker for renal tubular damage, and is useful to diagnose renal tubular damage and assess the extent of the damage.

To investigate the prevalence and distribution of chronic kidney disease(CKD) in Second Xiangya Hospital of Central South University.We retrospectively analyzed the medical records of 3547 CKD patients (or=14 years old) admitted to Second Xiangya Hospital for the 1st time from January 2003 to December 2008. Glomerular filtration rate (GFR) was estimated by using the MDRD equation abbreviated [eGFR=186.3*SCr-1.154*age-0.203*0.742 (for women) mL/min.1.73 m2]. Data of patients' gender, age, admission number, etiologic and functional diagnose, course of disease, blood pressure, hemoglobin, urine, renal function, blood albumin, and kidney ultra-B were collected.(1) The most common causes for CKD were primary glomerulonephritis(55.20%), hypertension (14.55%) and diabetes (11.78%). The composition of the causes during this 6 years was not significantly different (P0.05). The proportion of chronic glomerulonephritis declined while that of hypertensive nephropathy and diabetic nephropathy increased as time passed. (2) Patients were respectively distributed from stage 3 to stage 5 at the following percentages: 11.59% (stage 3), 23.03% (stage 4), and 65.38% (stage 5). Middle-aged and young patients (41 yearsage60 years) accounted for 39.24% of the CKD patients.Elderly patients (age60 years) accounted for 36.88% of the CKD patients. Chronic glomerulonephritis was often seen at 21-40 and 41-60 year olds. Patients with lupus nephritis were younger, 48.35% of whom were 21-40 years old. On the contrary, patients with hypertensive nephropathy and diabetic nephropathy were much older. They were mainly seen in older than 40 year groups. (3) Obstructive nephropathy and gout nephropathy occurred mainly in men while it seemed much easier for women to suffer from lupus nephritis. (4) The majority of CKD patients was accompanied by anemia (94.28%) and hypertension (56.91%), and the incidence and degree of anemia and hypertension increased as CKD developed (P0.005).The top 3 causes of CKD are chronic glomerulonephritis, hypertensive nephropathy, and diabetic nephropathy. The proportion of hypertensive nephropathy and diabetic nephropathy is on the rise. Elderly people are the high risk group for CKD.

The relationship between tonsillar autoimmune response and the pathogenesis of IgA nephropathy (IgAN) has been previously demonstrated. However, the role of CD4+CD25+ cells, which play critical roles in maintaining peripheral tolerance and preventing autoimmunity, has not yet been defined in IgAN.The lymphocytes from tonsils of all subjects (including 37 IgAN cases and 37 controls without renal diseases) were cultured for 72 hours without stimulation, or with stimulation by alpha-hemolytic streptococcus (HS) isolated from the tonsillar crypts of cases (the HS-IgAN) or controls (HS-controls). The CD4+CD25+ cells were measured by flow cytometry. Expression of J chain mRNA was analyzed by in situ hybridization (ISH) and the dimeric IgA-producing cells were identified by immunofluorescence and fluorescent ISH.The number of CD4+CD25+ cells was significantly lower in cases than in controls (0.98% +/- 0.204% vs. 3.58% +/- 0.554%, 1.37% +/- 0.214% vs. 5.78% +/- 0.562%, and 1.43% +/- 0.202% vs. 6.05% +/- 0.521%, for nonstimulation, HS-controls and HS-cases, respectively). CD4+CD25+ cells from cases showed a significantly lower stimulation index (SI) when stimulated with HS-controls and HS-IgAN than controls (p0.05), whereas the number of dimeric IgA-producing cells was significantly higher in cases than controls (11.9% +/- 3.1% vs. 6.5% +/- 1.5%, 33.5% +/- 5.7% vs. 13.9% +/- 1.2%, and 35.1% +/- 6.2% vs. 13.9% +/- 1.2%, for nonstimulation, HS-controls and HS-cases, respectively). The dimeric IgA-producing cells from patients with IgAN showed a significantly higher SI when stimulated with HS-controls, or HS-IgAN than those from patients without renal disease (p0.01). The SI of CD4+CD25+ cells was negatively correlated with that of dimeric IgA-producing cells.The results suggest that CD4+CD25+ cells and dimeric IgA-producing cells in tonsils may be related to the pathogenesis of IgAN.