Objective    To analyze the clinical, pathological data and outcomes of the adult patients with Henoch-Schönlein purpura nephritis (HSPN).    Methods     The data of 205 HSPN patients who were diagnosed in Kidney Disease Center of the First Affiliated Hospital of Zhejiang University between Jan 2004 and May 2013 were collected and analyzed in different groups.    Results The average age of the patients was (33±16) years old. All patients had purpura, 25% patients had abdominal symptoms and arthritis was reported in 18.5% patients. All patients reported hematuria; 32.7% patients were with urine protein less than 1 g/24 h and 21.9% patients had urine protein more than 3.5 g/24 h; 73.7% patients had normal level of glomerular filtration rate (eGFR, calculated by simplified MDRD equation); 14.1% patients had mild renal insufficiency [eGFR 60～90 ml·min-1·(1.73 m2)-1] and 12.2% patients were with eGFR less than 60 ml·min-1·(1.73 m2)-1. The type Ⅱ renal pathological changes were reported in 20.5% patients, 71.7% patients were with type Ⅲ, 7.3% patients were with type Ⅳ and only one patient had type Ⅴ pathological changes. The patients younger than 18 years had more abdominal involvement; the patients older than 50 years had higher levels of ESR, serum C reactive protein, serum IgA and more proportion of glomerular sclerosis, but lower eGFR level. Thirty-eight patients (18.5%) were lost follow up. The median follow-up of the other 167 patients was 15 months. The complete remission was reported in 124 patients (60.5%) and partial remission were reported in 15 patients (7.3%); 22 cases were unrelieved and 6 cases exhibited end stage renal disease (ESRD). The COX regression analysis revealed that old age was the independent risk factor of no relief and ESRD (P＝0.011, OR＝2.434).    Conclusion    The elderly HSPN patients has higher disease activity, more obvious decline in renal function and higher risk of treatment failure.

Objective    To assess the value of joint detection of serum cysteine proteinase inhibitors C (sCys-C), urinary kidney injury molecule 1 (uKIM-1), urinary neutrophil gelatinase-associated lipocalin(uNGAL) and urinary interleukin 18 (uIL-18) for early diagnosis of acute kidney injury (AKI) in critically ill patients.    Methods    A total of 256 adult patients who stayed Intensive Care Unit for 24 hours in the Third People's Hospital of Liaocheng between Aug 2011 and Dec 2012 were enrolled. According to Kidney Injury Net(AKIN) work, the patients were divided into non-AKI group and AKI group (including state 1, 2 and 3). The concentrations of urine NGAL, KIM-1, IL-18 and serum sCys-C were measured. The diagnosis value of four biomarkers joint detection and single detection for AKI were analyzed with the receiver operating characteristic (ROC) curve and the area under curve (AUC).     Results    (1) The levels of uNGAL, uKIM-1, uIL-18 and sCys-C were higher in patients with AKI than the patients with no AKI (P﹤0.01). (2) The area under curves of uNGAL, uKIM-1, uIL-18, sCys-C and joint detection were 0.742, 0.871, 0.803, 0.703, 0.925 respectively. (3) The sensitivity and specificity of parallel tests and serial tests of four biomarkers were 97.9%, 62.8%, 64.3% and 96.2% respectively. There were significant differences of sensitivity or specificity between single test and joint tests.    Conclusions    The urine NGAL, KIM-1, IL-18 and serum Cys-C are sensitive indexes for the early diagnosis of acute kidney injury. Joint detection has high value for early diagnosis of AKI.

Objective    To evaluate the changes of intestinal microflora in uremic patients and the relationship with inflammation.    Methods    Sixty uremic patients without hemodialysis, sixty uremic patients undergoing hemodialysis, and thirty healthy people as control were recruited in this study. Intestinal flora including Bifidobacterium longum, Lactobacillus acidophilus, Escherichia coli and Enterococcus faecalis were examed by Real-time PCR. The concentration of each bacterium was indicated by lg(copy/gram feces). Serum hypersensitive C-reactive protein (hs-CRP) were detected by immune nephelometry.    Results    The concentration of Bifidobacterium longum and Lactobacillus acidophilus was significantly lower in hemodialysis group (8.16±0.56 and 7.22±0.62) and non-hemodialysis group (8.25±0.51 and 7.42±0.59) than in control group (8.94±0.52 and 8.11±0.61, all P＜0.01). The concentration of Enterococcus faecalis and Escherichia coli were significantly higher in hemodialysis group (8.07±0.57 and 9.40±0.57) and non-hemodialysis group (8.06±0.55 and 9.47±0.50) than those of control group (7.75±0.55 and 9.11±0.54, all P＜0.01). There were no significant difference in the levels of these bacteria between non-hemodialysis and dialysis group. Stepwise regression analysis indicated that Lactobacillus acidophilus and Enterococcus faecalis were intimately correlated with hs-CRP (P＜0.05). The equation was: Yhs-CRP=57.97-9.91XLactobacillus acidophilus+2.26XEnterococcus faecalis.    Conclusions    The concentration of Bifidobacterium longum and Lactobacillus acidophilus decrease and Escherichia coli and Enterococcus faecalis increase in uremic patients. The decrease of Lactobacillus acidophilus and increase of Enterococcus faecalis may aggravate the microinflammation in uremic patients.

Objective    To explore the impacts of preeclampsia and the different extent of proteinuria on maternal and perinatal outcomes.    Methods    The retrospective analysis was conducted according to the perinatal clinical data of preelacmpsia, pregnancy-induced hypertension in pregnant women and normal pregnant women from the Fifth People's Hospital of Shanghai, excluding twins, diabetic mellitus and patients with chronic kidney disease previously. Patients were divided into three groups on the basis of their conditions: ① preeclampsia patients (A group, 220 cases); ② patients with gestational hypertension (B group, 189 cases); ③ normal pregnant (C group, 220 cases). Patients with pre-eclampsia according to the degree of proteinuria were further divided into three subgroups: A1: patients with mild proteinuria (n＝109); A2: patients with moderate proteinuria (n＝72); A3: patients with severe proteinuria (n＝39).    Results    Compared with the other two groups, the patients in A group had higher blood pressure, serum creatinine, uric acid, cesarean section rate, perinatal prematurity, stillbirth, fetal distress and neonatal asphyxia in preeclampsia group. However, the serum albumin level, eGFR, neonatal birth weight, length and Apgar scores were lower in A group compared with B and C group (P＜0.05). In three subgroups, serum creatinine level, uric acid level, cesarean section rate, perinatal prematurity and fetal distress were significantly increased in A3 group compared with A1 group, while the serum albumin level, eGFR, gestational age and neonatal birth weight were obviously lower in A3 group than in A1 group (P＜0.05). In patients with preeclampsia, 24 h urinary protein was negatively related with the levels of serum albumin and eGFR (P＜0.05), and positivly related with the blood pressure, serum creatinine and caesarean production rate (P＜0.05). Large amounts of proteinuria was a risk factor of adverse outcome for pregnant patients with preeclampsia (OR＝2.899，P＜0.05) .    Conclusions    Preeclampsia patients with large amount of proteinuria have poor maternal and perinatal outcomes. Massive proteinuria is a risk factor of adverse outcome for patients with pre-eclampsia.

Objective    To investigate causes and risk factors of peritoneal dialysis-related peritonitis, explore the pathogenic bacteria and drug sensitivity.    Methods    CAPD patients suffered peritoneal dialysis-related peritonitis were recruited in the First Affiliated Hospital of Nanjing Medical University in 2012. Gender, age and possible risk factors were analyzed by unvaried and multivariate logistic regression analysis. The causes, pathogenic bacteria, drug susceptibility, and validity treated with cefazolin plus ceftazidime were also analyzed.    Results    Thirty patients suffered peritoneal dialysis-related peritonitis and 129 peritoneal dialysis patients without peritonitis as control were included. The main causes for peritoneal dialysis-related peritonitis were nonstandard operating steps and intestinal infection. Multivariate logistic regression analysis showed that peritoneal dialysis-related peritonitis was significantly associated with higher CRP level. Of the peritoneal fluid culture, 26 cases were found positive and the positive rate was 76.47%, 19 cases (73.08％) were infected with Gram-positive cocci, 6 cases (23.08％) with Gram-negative bacillus and 1 case (3.85％) with fungi. Drug sensitivity test showed that Gram-positive cocci had the resistance rate to cefazolin(16.67％), and was sensitive to vancomycin in all cases. Gram-negative bacilli had the resistance to ceftazidime (20.00％), and was sensitive to imipenem and meropenem in all cases. All patients were given cefazolin plus ceftazidime as initial treatment. Twenty-seven cases were effective and the primary efficiency were 79.41％.    Conclusions    The main causes of peritoneal dialysis-related peritonitis in our centre were nonstandard operating steps and intestinal infection. The higher CRP level is an independent risk factor of peritoneal dialysis-related peritonitis. Gram-positive cocci are the main pathogenic bacteria leading to peritoneal dialysis-related peritonitis. There is lower resistance rate in Gram-positive cocci to cefazolin and Gram-negative bacilli to ceftazidime. Cefazolin plus ceftazidime can be an effective medicine on initiinal treatment of peritoneal dialysis-related peritonitis.

Objective    To explore the clinical significance of complement activation in IgA nephropathy (IgAN) patients and provide new potential therapy targets.    Methods    Biopsy-proven IgAN patients admitted in our renal center were retrospectively recruited. Demographic, baseline clinical and pathological data were recorded as well as the follow-up results. Patients were divided into three groups, negative, weak positive and strong positive group, according to the intensity of C3 deposition in mesangial area of glomurili. Decreased serum C3 level was defined as C3＜85 mg/dl. Results    In this study, 528 IgAN patients were recruited and mean follow-up time was 3 years. There were 119 (22.5%), 164(31.1%), 245(46.4%) patients in the negative, weak positive and strong positive group respectively; 93(21.7%) patients had decreased serum C3 level and 335(78.3%) patients had normal serum C3 level; Significant negative correlation was found between mesangial area of C3 deposition and serum level of C3(r＝-0.209, P＜0.01). The age or sex were similar among different groups of mesangial C3 deposition. In univariate analysis, higher baseline serum creatinine, uric acid and IgA levels, and lower estimated glomerular filtration rate(eGFR), body mass index (BMI) levels were associated with a higher grade of mesangial C3 deposition (P＜0.05). Endocapillary hypercellularity and tubular atrophy or interstitial fibrosis were more prominent in patients with higher grade mesangial deposition of C3. Compared with the patients with normal serum C3 level, patients with decreased serum C3 level had lower white blood cells, hemoglobin, triglyceride, cholesterol, eGFR level and higher serum creatinine level (P＜0.05).  During the follow-up, a total of 54 patients developed to end stage renal disease (ESRD), the incidence of ESRD was 23.7% in patients with decreased serum C3 level and 8.4% with normal C3 level. Kaplan-Meier analysis showed that median outcome-free survival time of patients with decreased serum C3 level was significant shorter than patients with normal serum C3 level [(145.0±22.5) months vs (150.8±17.0) months, P＜0.01]. Cox regression proportional hazards models showed that after adjusting by sex, age and clinical indicators (MAP, eGFR, serum albumin, urine protein and hemoglobin level),  decreased serum C3 level (HR＝0.97, 95%CI 0.96, 0.99, P＜0.01) remained be an independent risk factor of ESRD.    Conclusions    There are different levels of complement activation in patients with IgAN. Complement activation is associated with baseline renal function and clinical outcomes, and decreased serum C3 level is an independent risk factor of ESRD in IgAN patients. Complement activation may be involved in the progression of IgAN.

Objective    To investigate the microbial spectrum and antibiotic resistance of continuous ambulatory peritoneal dialysis (CAPD) related peritonitis and guide the clinical rational use of antimicrobial agents.    Methods    A retrospective analysis was made of CAPD related peritonitis in 236 cases with peritoneal dialysate culture results in the Second Hospital Affiliated to Soochow University from Jan 1, 2009 to Jun 30, 2013. Distribution of pathogenic bacteria and its resistance to common antibiotics were analyzed.    Results    Among 236 cases of peritoneal dialysate cultured cases, 185 cases were positive (78.39%). A total of 193 strains were cultured, including 138 Gram-positive strains (71.50%), 44 Gram-negative strains (22.80%) and 11 fungi (5.70%). Eight cases of polyinfection were found and 2 strains were cultured. The isolated organisms included Simple Gram-positive organisms in 5 cases, mixed Gram-positive and Gram-negative organisms in 3 cases. Drug sensitivity test of the Gram-positive strains showed that antibiotics with the lowest resistance were vancomycin (0), Teicoplanin(0), linezolid(0). Drug sensitivity test of the Gram-negative bacteria showed that antibiotics with the lowest resistance were amikacin(0), imipenem(0), meropenem(0), Cefoperazone/sulbactam(0). The isolated bacteria were resistant to multiple antibiotics. A total of 236 cases of 9 patients died in 236 cases, including 3 cases of fungal infection, 3 cases of Gram-negative bacteria infection, 2 cases of Gram-positive bacteria infection, one cases of culture-negative. Peritonitis related mortality rate was 3.81%; 13 cases transferred to hemodialysis, including 6 cases of fungal infection. The total catheter removal rate was 5.51%. 10 cases gave up treatment, the others were cured. The cure rate was 86.44%.    Conclusions   The main pathogen of CAPD related peritonitis is Gram-positive bacteria. Traditional treatment of peritonitis with first generation combined third generation cephalosporins is not suitable for CAPD related peritonitis. The empiric initial treatment of peritonitis recommended the use of vancomycin combined Cefoperazone/sulbactam or amikacin .

Objective    To test the availability of the SF-36 scale for the Chinese patient with Fabry disease (FD), the quality of life(QOL) and its probable influence factors were analyzed.    Methods    The data were obtained from 50 healthy volunteers and 57 patients with FD enrolled in nephrology department of Ruijin hospital from Jan, 2003 to Jan, 2013. The SF-36 scale was used to evaluate the QOL of patients and to compare the difference between the patients and controls. Furthermore, the influencing factors were estimated by multiple linear regressions.    Results    Between the patients and controls, the differences of 8 dimensionalitiy's scores had statistical significance, which claimed that the reaction was sensitive. Especially, in the patient group, the Pearson correlation coefficient among each domain of the SF-36 was lower than its Cronbach's α coefficient (0.934), which indicated good internal consistency reliability. The two common factors were much the same to the theory assume, which illustrated the construct validity was available. Even the acceptability of the patient’ group at 100% proved the scale was appropriate for patients with FD. In addition, in role-physical (RP) and bodily pain (BP) , the scores of the male patients were less than the females (P﹤0.01), declared that the QOL of the males was inferior to the females. In the physical function (PF) and the mental health (MH), the scores of the patients with angiokeratoma were less than the group without it, so the patients who had evident clinical symptoms more likely contributed to depression. Using multiple linear regression, age, gender and clinical types were chosen into regression equation by stepwise regression, and the main potential predictor was age.    Conclusions    The SF-36 scale applies to evaluate the QOL of patients with FD. It is critical to concern and manage the QOL of FD patients, especially in their mental health aspect.

Objective    To explore the effects of BSA on hypoxia inducible factor/hypoxia response element (HIF/HRE) transcription activity in rat tubular epithelial cells (NRK-52E) with HRE-Luc reporter plasmid.    Methods    Luciferin activity of NRK-52E cells incubated by a medium contained BSA in varying concentration (0, 5, 10, 20 mg/ml) and stimulus duration (24, 48, 72 h) was detected by dual luciferase detecting system based on HRE-Luc reporter plasmid and HIF-1α expression was detected by Western blotting.    Results    HIF/HRE transcription activity of NRK-52E cells was increased in BSA incubation group (10 mg/ml, 48 h) compared with blank control (BSA 0 mg/ml, 48 h) [(2.59±0.35) vs (1.03±0.09), P=0.000]. HIF-1α expression of NRK-52E cells was increased in BSA incubation group (20 mg/ml, 48 h) compared with blank control (BSA 0 mg/ml, 24 h) [(0.052±0.010) vs (0.014±0.003), P=0.000].    Conclusion    Albumin can increase HIF/HRE transcription activity of TEC.

Objective    To investigate the role of IQ domain GTPase-activating protein 1 (IQGAP1) in angiotensinⅡ(AngⅡ) -induced podocyte apoptosis and the underlying mechanism. Methods    Differentiated mouse podocytes were exposed to AngⅡ at different concentrations for 6 h or at 10-8 mol/L for variable incubation time. Podocyte apoptosis was assessed by flow cytometry. Expression of IQGAP1 was analyzed by immunofluorescence and Western blotting. IQGAP1 siRNA and MAPK pathway inhibitors(10 μmol/L SB202190, 25 μmol/L SP600125, 10 μmol/L U0126) were further introduced to investigate the role of IQGAP1 and MAPK signalings in the process. And co-immunoprecipitation was used to evaluate the interaction between ERK1/2 and IQGAP1.    Results    (1) AngⅡ promoted podocyte apoptosis in a dose- and time-dependent manner. (2) IQGAP1 was located in celluar membrane and cytoplasm of cultured podocytes. Exposure to AngⅡ stimulated IQGAP1 expression in a dose- and time-dependent manner, and elevated phosphorylation of p38, JNK, and ERK1/2 simultaneously. (3) Pretreatment with SB202190, SP600125, or U0126 dramatically prevented AngⅡ-promoted podocyte apoptosis respectively (P＜0.05). However, the protein level of IQGAP1 was not altered. (4) Knockdown of IQGAP1 with siRNA obviously prevented AngⅡ-induced apoptosis of podocytes(P＜0.05) and reduced AngⅡ-induced phosphorylation of ERK1/2(P＜0.05), but not that of p38, JNK. This was accompanied by a reduced interaction between ERK1/2 and IQGAP1(P＜0.05).    Conclusion    IQGAP1 contributes to AngⅡ-induced podocyte apoptosis by interacting with the ERK1/2 signaling protein.

Objective    To investigate the expression changes and significance of Pdlim2 in the glomerular podocyte of hyperlipidemic rats.    Methods    Forty-five individuals of SD rats were divided randomly into 3 groups (n＝15 in each group). The control group was fed with normal diet. The high fat group was fed with high fat diet. The simvastatin group was fed with high fat diet plus with simvastatin gavage (10 mg·kg-1·d-1). Five rats were sampled randomly from each group at week 4, 6, and 10 and the urinary protein excretion, the concentration of serum cholesterol, and the concentration of low density lipoprotein cholestorol were determined, the glomerular podocyte damage in rats was detected by electron microscope, the expression of Pdlim2 protein was determined by immunohistochemistry and by Western blotting.    Results    The levels of serum cholesterol and low density lipoprotein cholestorol increased significantly in high fat group and simvastatin group at week 4 compared to that in control group(P＜0.05), and the level in simvastatin group was significantly decreased compared with that in high fat group(P＜0.05). The urinary protein levels of high fat group and simvastatin group were significantly higher than that in control group at week 10, and the level in simvastatin group was significantly decreased in high fat group, there was significant difference in each group of comparison(P＜0.05). Podocyte injury was detected by electronic microscopy in high fat group at week 4, and the injury became more serious as the treatment time increased. Podocyte injury in the simvastatin group was significantly less than that in the high fat group and the control group at week 10. The positive staining of Pdlim2 was mainly in the glomeruli and the expression of Pdlim2 of the high fat group was lower than the simvastatin group, and both were lower than the control group at week 10. The expression of Pdlim2 protein of high fat group was lower than that in the control group since week 4(P＜0.05). The expression of Pdlim2 protein of high fat group was lower than that in the simvastatin group(P＜0.05), and both were lower than the control group at week 10(P＜0.05).    Conclusions Hypedipidemia induces podocyte injury before urinary protein, which is suggested to be associated with the decrease of Pdlim2 protein. Simvastatin reduces podocyte foot processes of high fat induced fusion, which may be through protecting the expression of glomerular Pdlim2.