Objective    To investigate the efficacy and safety of immunosuppressive therapy (Tacrolimus or CTX) in primary IgA nephropathy (IgAN) with mild or moderate renal dysfunction. Methods  Thirty-six primary IgAN patients diagnosed by renal biopsy, with mild or moderate renal dysfunction[30 ml•min^-1•(1.73 m²)^-1≤eGFR＜90 ml•min^-1•(1.73 m²)^-1, proteinuria＞1.0 g/24 h] were recruited in this randomized controlled trial. All the patients were assigned into steroid therapy alone, steroid combined with CTX (CTX group) and steroid combined with tacrolimus (tacrolimus group).    Results    The 24-hour proteinuria at baseline were (1.91±0.81) g/24 h, (2.42±1.46) g/24 h, (2.57±1.87) g/24 h in steroid group, CTX group and tacrolimus group respectively. Compared with baseline, it was significantly decreased in steroid group at 3 months [(0.90±0.75) g/24 h, P＜0.05], 6 months [(0.76±0.73) g/24 h, P＜0.05] and 12 months [(0.35±0.35) g/24 h, P＜0.05], in CTX group at 3 months [(1.40±1.24) g/24 h, P＜0.05], 6 months [(0.87±0.83) g/24 h, P＜0.05]  and 12 months [(0.68±0.70) g/24 h, P＜0.05], and in FK506 group at 3 months [(1.10±1.33) g/24 h, P＜0.05], 6 months [(0.78±0.69) g/24 h, P＜0.05] and 12 months [(0.69±0.82) g/24 h, P＜0.05]. At 6 months, serum creatinine were decreased in steroid alone [(111.72±31.23)  μmol/L vs (121.17±36.51) μmol/L, P＜0.05] and in CTX group [(111.33±22.76) μmol/L vs (124.33±35.51) μmol/L, P＜0.05], while no significant difference was detected in  tacrolimus group. At 12 months, there was no significant difference in terms of serum creatinine in all three groups. Besides, there was no significant difference in terms of eGFR (CKD-EPI) in all three groups. One case presented hyperglycemia and one case had liver dysfunction during the treatment in steroid group. Two cases had hyperglycemia, one case had impaired glucose tolerance and one case had liver dysfunction in the  tacrolimus group.    Conclusions    Steroid along, steroid combined with tacrolimus or combined with CTX are efficient in reducing urine protein in the treatment of primary IgAN with mild or moderate renal dysfunction without inducing increased serum creatinine. Given the occurrence of hyperglycemia during the treatment with steroid combined with tacrolimus, it is important to monitor  tacrolimus concentration during the treatment.

Objective    To explore the levels of serum 25(OH)D in glomerular disease patients and investigate its influence on the impaired glucose metabolism after treated with glucocorticoid. Methods    A total of 61 patients with glomerular disease confirmed by clinical diagnosis and renal biopsy were included in the case group before receiving steroid therapy. 16 cases were selected as control at the same period. Before and six weeks after the treatment of glucocorticoid, all subjects took oral glucose tolerance test (OGT). According to the results of OGT, patients were divided into normal glucose regulation (NGR) group, impaired glucose regulation (IGR) group and steroid diabetes mellitus(SDM) group. Serum 25(OH)D levels were detected with enzyme-linked immunosorbent assay (ELISA), and other clinical data including albumin(Alb), Scr and urine protein were collected.    Results    (1) Before treated with glucocorticoid, the serum 25(OH)D levels in the control group [(64.09±13.53) nmol/L] were significantly higher than that in NGR group [(50.81±12.44) nmol/L], while the latter was significantly higher than that in IGR group [(42.71±8.09) nmol/L, all P＜0.05]. In the glomerular disease patients, 18 cases (29.51%) were 25(OH)D insufficiency and 39 cases(63.93%) were 25(OH)D deficiency. 25(OH)D levels in patients with nephritis were significantly higher than in patients with nephroitic syndrome[(56.94±10.41) nmol/L vs (45.88±11.55) nmol/L, P＜0.05]. (2)6 weeks after the treatment, incidence of steroid diabetes in IGR group was significantly higher than that in NGR group (61.11% vs 20.93%, P＜0.05). Baseline levels of 25(OH)D in NGR group and IGR group were all significantly higher than that in SDM group [(55.68±13.09) nmol/L, (48.97±9.91) nmol/L vs (40.91±7.82) nmol/L, all P＜0.05]. (3)Serum levels of 25(OH)D were positively correlated with serum albumin and serum calcium, and negatively correlated with BMI, urinary protein, cholesterol and the 2 hours postprandial blood glucose. (4)Logistic regression analysis indicated that 25(OH)D＜50 nmol/L and HbA1c＞5.6% increased the risk of developing steroid diabetes 5.586  and 5.197 times, respectively. Age increased 10 years or insulin resistance index increased one, the risk of occurred SDM increased 2.443 and 2.755 times, respectively.    Conclusions    Most glomerular disease patients are serum 25(OH)D deficiency or insufficiency. Low level of serum 25(OH)D is one of the main risk factors of steroid diabetes in patients with glomerular disease when treated with glucocorticoid.

Objective    To investigate the types and outcome of vascular access in patients with end stage renal disease (ESRD) initiated hemodialysis (HD), and provide the basis for advancing the proportion of planned HD with arteriovenous fistula (AVF).     Methods    Clinical data, vascular access types at the initiation of HD, the outcomes of all types of dialysis access and the conversion of renal replacement therapy of ESRD patients who initiated HD in the first affiliated hospital of zhejiang university between January 2009 and December 2011 were retrospectively studied.    Results    A total of 836 patients were included in our study. Among them 510 were males and 326 were females. The average age was (49.77±17.65) years old. The major primary diseases were primary glomerular disease (72.73%), diabetic nephropathy (11.60%)and hypertensive nephrosclerosis (3.95%). Only 73 patients (8.73%) used AVF as the vascular access at the initiation of HD, another 763 patients (91.27%) used central venous catheter. Six months after the start of dialysis, 542 patients (81.5%) had used AVF as permanent vascular access, 123 patients (18.5%)had used the tunneled cuffed catheter, 54 patients had received a transplant and 55 patients had converted to peritoneal dialysis. The results of logistic regression analysis suggested that being male, patients from outside hangzhou and patients whose glomerular filtration rate were lower than 5 ml•min^-1•(1.73 m²)^-1 were the risk factors of using central venous catheters at the initiation of HD.   Conclusions    Only a minority of patients used AVF at the initiation of HD, but most of the other patients switched to AVF  within the following six months. Increasing the proportion of AVF as the vascular access of planned HD is still our current goal.

Objective    To examine the effects of different compositions of metabolic syndrome[Overweight and (or) obesity, hyperglycemia, hypertension, dyslipidemia] on chronic kidney disease. Methods    A total of 1552 health data were collected from the survey of chronic kidney diseases among Uygur adults in Moyu country in Xinjiang Uygur Autonomous Region and the relationship between metabolic syndrome and chronic kidney disease was analyzed by using SPSS 15.0 software package.    Results    Before and after adjusting of age and gender, the prevalence of metabolic syndrome was 14.18% and 14.45% (95% CI 14.30%-14.60%). The prevalence of albuminuria (7.27% vs 3.83%, χ²=5.42, P=0.02), reduced estimated glomerular filtration rate (9.55% vs 3.45%, χ²=16.96, P=0.00) and chronic kidney disease(13.64% vs 6.76%, χ²=12.52, P =0.00) increased in residents diagnosed as metabolic syndrome than those without metabolic syndrome. The prevalence of chronic kidney disease increased with the increasing number of metabolic syndrome elements.    Conclusions    The prevalence of chronic kidney disease is associated with the accumulation of metabolic syndrome compositions. Early intervention on metabolic risk factors may reduce the risk of chronic kidney disease.

Objective    To explore the relationship between reversed dipper blood pressure (BP) pattern with target organ damage in Chinese chronic kidney disease (CKD) patients.    Methods    A total of 1 116 CKD patients from the Third hospital of Sun Yat-sen university were enrolled from May 2010 to April 2014, all of whom carried ambulatory blood pressure monitoring (ABPM), and clinical data and ultrasonography were collected.    Results    Total of 23.39% CKD patients were reversed dipper BP pattern, 46.95% patients were non-dipper BP pattern, and dipper BP pattern was only 27.15%. Compared with dipper and non-dipper BP pattern group, patients with reversed dipper BP pattern had higher left ventricular mass index (LVMI), lower estimated glomerular filtration rate (eGFR) and severely damaged left ventricular diastolic function (all P＜0.0083). After multiple linear regression analysis, reversed dipper BP pattern was an independent predictor for determining eGFR and LVMI. Age, lower hemoglobin and combination of diabetes were independently associated with reversed dipper BP pattern.    Conclusion  Reversed dipper BP pattern is common in Chinese CKD patients, which is closely related to renal damage and cardiovascular injuries.

Objective    To investigate the survival of older patients with iliac vein tunneled cuffed  catheters on maintenance hemodialysis.     Methods    A total of 70 older patients with external iliac vein tunneled cuffed catheters on maintenace hemodialysis were included in this study, there were 94 patients with internal jugular vein tunneled cuffed catheters as control group. The baseline anthropometric and 1aboratory parameters were measured. The catheter dysfunction and catheter related complications were documented.    Results    There were lower survival rate and catheter survival in the external iliac vein group compared with internal jugular vein group（χ²=13.714, P＜0.01; χ²=13.093, P＜0.01）. Compared with internal jugular vein group, there was lower rate of catheter infection in external iliac vein group(χ²=9.416, P＜0.01); In addition, there were higher rate of cardiovascular disease(CVD) events and catheter dysfunction among patients in external iliac vein group (χ²=7.492, P＜0.01; χ²=5.912, P＜0.05). Furthermore, the incidence of catheter dysfunction and cardiovascular disease events were the independent risk factors of mortality for older patients with iliac vein tunneled cuffed catheters on maintenance hemodialysis by Cox regression model.    Conclusions    Patients with iliac vein tunneled cuffed catheters have a shorter survival time. Those with catheter dysfunction or cardiovascular disease events are in higher risk of mortality．

Objective    To examine whether aldosterone contribute to obesity related glomerular disease.    Methods    C57BL/6J mice were randomly divided into three groups: a control group (low-fat-diet, n=10), a model group (high-fat-diet, n=10) and a intervention group (high-fat-diet, n=12). After 8 weeks intervention group were treated with a mineralocorticoid receptor antagonist, spirolactone (SPL).The physicochemical indexes and the renal pathology of the three groups were all detected. The mRNA and protein expressions of podocyte marker protein were determined by real-time PCR and Western blotting, respectively.    Results    Compared with the control group, body weight, kidney weight, Lee’s index, fat index, blood cholesterol, blood triglyceride, creatinine clearance rate, urinary protein excretion, glomerular average diameter, glomerular foot process average width were significantly up-regulated (P＜0.05); The mRNA and protein expression of nephrin, podocin, podoplanin and podocalyxin were significantly down-regulated in model group (P＜0.05). Meanwhile, these changes were attenuated by SPL.    Conclusion    Aldosterone can participate in the process of obesity- related renal injury, and these can be attenuated by mineralocorticoid receptor antagonist, spirolactone. This gives us preliminary clues to treat ORG.

Objective    To explore the expression of DC-SIGN, the phenotype of dendritic cells (DCs), on podocytes, and its role in immune and inflammatory responses of lupus nephritis (LN).     Methods    DC-SIGN and IgG1 expression in renal tissues of lupus nephritis patients were observed by immunohistochemistry and immunofluorescence. The 4-week old LN mice were randomly divided into the experimental group and the intervention group. C57BL/6J mice were used as normal control group. Mice of the intervention group were injected anti-DC-SIGN antibody at 6-week old. Mice were sacrificed at 16, 20, 24, 28-week old respectively, to observe the mice renal function and pathological changes. And DC-SIGN and IgG1 expression in renal tissue were observed by immunohistochemistry and immunofluorescence. In addition, mice podocytes were treated with serum of LN mice. Flow cytometry was used to investigate the expression of MHC II, CD80 and DC-SIGN expression on podocytes. Mixed lymphocyte reaction was used to detect the ability of stimulating T cells proliferation. IFN-gamma and IL-4 in supernatant were determined by ELISA.    Results    (1) Expression of DC-SIGN and IgG1 was found in glomeruli of lupus nephritis patients. (2) Accompanied by increased proteinuria of LN mice from 20-week old (P＜0.01), DC-SIGN and IgG1 expression was found in glomeruli, and the renal function deteriorated up to 24 week-old (P＜0.01). Mice with anti-DC-SIGN antibody intervention appeared reduced proteinuria and remission of renal function (P＜0.01). (3) After stimulated by serum of LN mice, the expression of DC-SIGN, MHC II and CD80 was up-regulated, stimulation of T cell proliferation was enhanced (P＜0.01), and IFN-gamma/IL-4 ratio increased (P＜0.01). Anti-DC-SIGN antibody treatment down-regulated the expressions of DC-SIGN, MHC II and CD80 on podocytes, decreased the ability of stimulating T cell proliferation and lowered the ratio of IFN-gamma/IL-4 (P＜0.01).    Conclusions    Podocytes in lupus nephritis can play DC-like function through the expression of DC-SIGN, which may be involved in immune and inflammatory responses of renal tissue. However, inhibiton of DC-SIGN can depress immune function of podocytes and have prevention and treatment effect.

Objective    To explore the effects of human umbilical cord mesenchymal stem cells(HUC-MSCs) on podocytic apoptosis and injury induced by high glucose (HG) and the underlying mechanisms.    Methods    Podocytes were divided into six groups according to treatment: ⑴ normal glucose group (NG); ⑵ high glucose group (HG); ⑶ mannitol control group (NG+Ma); ⑷ HUC-MSC co-culture group (HUC-MSCs); ⑸ recombinant human hepatocyte growth factor treatment group (rhHGF); ⑹ neutralizing antibody group(HGF-NtAb). Cytometry and Hoechst staining were used to detect the apoptosis rates. Western blot was used to measure the ratio of active PARP to total PARP and the level of Bcl-2. Immunofluorescence was used to study podocytic apoptosis and injury. Neutralizing antibody (NtAb) was used to block its function and the recombinant cytokine was added to induce its function. Results    High glucose induced podocytic apoptosis in a time-dependent manner, HUC-MSCs co-culture decreased the podocytic apoptosis rate and the expression of PARP (all P﹤0.05), increased the expression of Bcl-2, prevented the reduced expression and maintained the normal arrangement of podocytic podoplanin. The rhHGF prevented podocytic apoptosis and injury similarly to HUC-MSCs, the beneficial effect of HUC-MSC decreased when blockade of HGF.    Conclusions    HUC-MSCs co-culture ameliorates podocytic apoptosis and injure induced by HG, probably through secreting soluble HGF.