Objective To retrospectively investigate the pathological and clinical characteristics of diabetic nephropathy and non-diabetic nephropathy diagnosed with renal pathology. Methods Data of 110 patients diagnosed as type 2 diabetes mellitus combined with chronic kidney disease (CKD) and conducted renal biopsy from January 2004 to December 2013 in our hospital were retrospectively analyzed. According to pathological diagnosis, patients were categorized into three groups: DN group, NDRD group and DN with NDRD group (MIX group). Results Membranous nephropathy was the most prevalent pathological type in NDRD group while IgA nephropathy was the major pathological type in MIX group. Compared with NDRD, DN patients had a higher anemia and diabetic retinopathy(DR) rate (all P＜0.05). The prevalence of having both nephrotic range proteinuria and kidney function decrease was higher in DN than NDRD (P＜0.05). Conclusions Renal pathology is important for the differential diagnosis of DN and NDRD since there is a relatively high rate of NDRD in patients with type 2 diabetes mellitus and CKD.

Objective To investigate the relationship between carotid artery intima-media thickness and renal function in patients with diabetes mellitus. Methods 424 patients of type 2 diabetes without dialysis were enrolled in a cross-sectional study. According to their artery intima-media thickness (IMT), the patients were divided into normal group and higher IMT group. All patients according to UAER or 24h urinary protein were divided into normal proteinuria group, micro-proteinuria group and clinical proteinuria group. The biochemical examination, eGFR, and atherosclerotic plaque of different groups were compared. Pearson or spearman correlation was used to analyze the relationship between eGFR, IMT and other parameters. Risk factors for eGFR decline were analyzed by binary logistic regression. Results Compared with normal group, patients in the higher IMT group were older [(63.3±10.2) year vs (52.5±10.6) year, P﹤0.05], and underwent longer duration of diabetes [(8.9±6.7) year vs (6.2±5.7) year, P﹤0.05]. Their level of eGFR was decreased [(75.92±28.00) ml/min vs (91.64±24.05) ml/min, P﹤0.05], while plaque incidence (71.3% vs 18.3%，χ2=112.42, P﹤0.01) and prevalence of hypertension (56.4% vs 29.6%, χ2=27.22, P﹤0.01) increased. Correlation analysis showed that IMT was positively correlated with age (r=0.503, P﹤0.01), duration of diabetes (r=0.204, P﹤0.01), 24 h urine protein (rs=0.175, P﹤0.05), plaque (rs=0.562, P﹤0.01), and hypertension (rs=0.193, P﹤0.01), but negatively correlated with eGFR (r=-0.307, P﹤0.01). Logistic regression analysis showed that age, serum uric acid, 24 h urine protein and carotid artery intima-media thickness were independent risk factors for eGFR decline [OR=1.115, 95%CI(1.053, 1.165), P﹤0.001; OR=1.008，95%CI (1.002, 1.014), P=0.006; OR=1.492, 95%CI(1.170，1.903), P=0.001; OR=1.619, 95%CI(1.121, 2.339), P=0.010]. Conclusion Carotid artery intima-media thickness is an independent risk factor for kidney function decline in patients of diabetes.

Objective To investigate the exercise performance in maintenance dialysis patients, and analyze its correlative factors. Methods Maintenance dialysis patients admitted in Tongji Hospital of Shanghai from December 2014 to March 2015 were enrolled, with their baseline data and biochemical measurement being collected. The anthropometric indexes including arm circumference, triceps skinfold, waist circumference and hip circumference were detected. The exercise activity was assessed by hand grip test, timed up and go test (3mTUG) and five times sit-to-stand test (FTSST). Patients were divided into fast group (3mTUG≤12 s) and slow group (3mTUG＞12 s). Univariate and multivariable analyses were used to evaluate the factors influencing exercise performance in maintenance dialysis. Results There were 121 patients enrolled: 62 on peritoneal dialysis and 59 on hemodialysis, 76 men and 45 women. Patients' average age was (61.6±13.0) years and median dialysis age was 31.7(12.3, 69.0) months. There was no statistical difference between fast group (n=80) and slow group (n=41) in gender, dialysis method, dialysis age, body mass index (BMI), arm muscle area (AMA), waist-hip ratio (WHR), hemoglobin (Hb) and total cholesterol (TC). Patients in fast group were younger, had higher serum albumin, prealbumin, serum phosphate and iPTH, and less prevalence of diabetes than those in slow group. In exercise activity, patients in fast group had better performance in handgrip, 3mTUG and FTSST (all P＜0.05). Univariate analysis showed that, handgrip was correlated with sex (male), AMA, BMI, age, diabetes, serum phosphorus and TC; scores in FTSST was correlated with age, BMI, diabetes, WHR, dialysis method, dialysis age, prealbumin and serum phosphorus; scores in 3mTUG was correlated with age, diabetes, WHR, dialysis method and dialysis age, prealbumin, serum phosphorus and iPTH (all P＜0.05). Multiple stepwise regression analysis showed that sex (male), age, AMA and diabetes were independently correlated with handgrip in dialysis patients (all P＜0.05); age, dialysis method, BMI and diabetes were independently correlated with scores in FTSST (all P＜0.05); age, dialysis method, diabetes and WHR were independently correlated with scores in 3mTUG (all P＜0.05). Conclusions The exercise performances of patients on maintenance dialysis are impaired. Age and diabetes are independent factor associated with the exercise performances of patients on maintenance dialysis. AMA is independently associated with upper limb movement, and dialysis method, BMI and WHR are independent factors associated with lower limb movement in dialysis patients.

Objective To investigate vascular access modalities at initiation of hemodialysis for end stage renal disease (ESRD) patients in hospitals of different levels, and to analyze the reasons contributing to the absence of arteriovenous fistula (AVF) during initial hemodialysis. Methods A pre-designed questionnaire was used to collect the information of patients that entered hemodialysis within five years, including basic information and their first vascular access types, and analyze the factors that influence patients' AVF use. Results (1) According to the 203 questionnaires returned from 5 hospitals, central venous catheter (CVC) was chosen by 122 (60.1%) patients, direct arteriovenous puncture by 44 (21.7%) patients, AVF by only 35 (17.2%) patients, and long-term cuffed catheter by 2 (1.0%) patients. For patients in different hospitals, 61.7% of patients in Jiamusi Hospital used direct arteriovenous puncture, while CVC were used most in the other four hospitals. The leading reason contributing to the absence of AVF was patient's refusal [75 cases (44.6%)], among which patients regarding AVF psychologically unacceptable accounted for the most [44 cases (26.2%)]. Following that were 45 cases (26.8%), in which patients were uninformed of AVF and 38 cases (22.6%) caused by time limitation. (3) Logistic regression showed well-educated, female, and urban residential patients were more likely to choose AVF at initiation of hemodialysis. Conclusion The percentage of AVF utility at the start of hemodialysis remains low, with situation varying in different hospitals and regions. Multiple factors are associated with vascular access modalities, among which the influence of doctors cannot be ignored. More efforts should be spared on patient education to improve the dialysis quality of ESRD patients in China.

Objective To investigate the relationship between fetuin A and left ventricular function and their influences on residual renal function(RRF) in peritoneal dialysis patients. Method Eighty patients recently initiating peritoneal dialysis were enrolled into this study and were divided into high fetuin A group and low fetuin A group accordin to the value of serum fetuin A concentration. Hemoglobin, high sensitive C reactive protein(hsCRP), calcium, phosphorus, albumin, lipoproteins and left ventricular myocardial performance index(LV-MPI) were examined. All these patients were followed up for 12 months, to discover the parameters’ differences between two groups and to investigate the association between fetuin A and left ventricular function and RRF. Results At the beginning of the study, there was no difference of hsCRP, calcium, phosphorus, albumin, lipoproteins and LV-MPI, estimated glomerular filtration rate (eGFR) between two groups; After 12 months follow-up, MPI was obviously shorter (P＜0.05) and RRF was obviously higher (P＜0.05) in high fetuin A group than thosein low fetuin A group. Compared with the beginning of the study, LV-MPI was significantly increased and eGFR was significantly decreased after 12 months follow-up (both P＜0.05) in low fetuin A group, but no obviously change of LV-MPI or eGFR was found in high fetuin A group after follow-up. Pearson correlation analysis discovered an obvious negative correlation between fetuin A and MPI (r=-0.680, P＜0.01). Multiple regression analysis indicated that eGFR had positive correlation with fetuin A (B=0.058, t=3.679, P＜0.01) and negative correlations with MPI (B=-0.511, t=-2.903, P=0.007), age(B=-0.144, t=-4.013, P＜0.01). Diabetes was risk factor to loss of RRF (B=-2.031, t=-2.759, P＜0.05). Conclusion Fetuin A has very close relationship with left ventricular function.Decreased serum fetuin A level and decreased left ventricular function are risk factors to the loss of the RRF in ERSD patients.

Objective To evaluate the expression of secreted frizzled related protein 4 (sFRP4) in autosomal dominant polycystic kidney disease(ADPKD) and the effect of sFRP4 induced apoptosis in ADPKD. Methods (1)Serological method: serum samples of 12 healthy people and 20 ADPKD patients were collected and the levels of sFRP4 in serum were detected by ELSIA assay. (2)Tissue experiments: normal renal tissue was collected from radical nephrectomy for renal carcinoma; polycystic renal tissues were taken from ADPKD patients. The expression of sFRP4 in renal tissues was observed by immunohistochemistry; Real-time PCR was used to explore the mRNA level of sFRP4 and caspase-3; TUNEL method was applied to observe the apoptosis cells existing in ADPKD. (3)studies in vitro: HEK-293T cells were transfected with PcDNA6 and Flag. sFRP4.PcDNA6 respectively, after which Western blotting was performed to detect the expression of caspase-3 protein and flow cytometry was performed to estimate cell apoptosis rate. Results (1)ELISA results showed serum concentrations of sFRP4 in ADPKD were markedly higher than normal control (P＜0.05). (2)Compared with normal renal tissues, the sFRP4 expression was dramatically increased in ADPKD and mainly distributed in the cytoplasm of renal tubular epithelial cells. (3)Real-time PCR showed the expression of sFRP4 and Caspase-3 mRNA in ADPKD were up-regulated comparing with those in normal control (P＜0.05). (4)TUNEL assays revealed that elevated apoptosis appeared in tubular epithelial cells of ADPKD. (5)The level of caspase-3 protein and apoptosis rate were significantly increased after over-expressed sFRP4 in HEK-293T cells (all P＜0.05). Conclusions The expression of sFRP4 is strikingly up-regulated in ADPKD. In addition, abnormal apoptosis of tubular epithelial cells exists in ADPKD and over-expressed sFRP4 can induce apoptosis of HEK-293T cells. This phenomenon may be attributed to the elevated sFRP4.

Objective To investigate the effect and mechanism of soluble epoxide hydrolase inhibitor (sEHI) for NF-κB pathway and cell circle arrest of tubular epithelial cell in unilateral ureteral obstruction (UUO) mice model. Methods Thirty-two healthy C57BL/6 male mice performed UUO surgery to induce renal interstitial fibrosis. Animals were randomly divided into 4 groups: sham group (n=8), sEHI (1 mg?kg-1?d-1) group (n=8), UUO group (n=8) and UUO+sEHI (1 mg?kg-1?d-1) group (n=8). Daily sEHI [1-(1-methylsulfonyl-piperidin-4-yl)-3-(4-trifluoromethoxy-phenyl)-urea, TUPS] or 2% DMSO was applied to mice by oral gavage from day 1 to day 14 after surgery. All mice were sacrificed at day 14 and kidneys were harvested for further analysis. The changes of renal tissue morphology and pathology were observed by Hematoxylin and eosin (HE) and sirius red staining. The expressions of sEH, nuclear factor κB p65 (NF-κB p65) and IκB were measured by Western blotting. The expressions of TNF-α, IL-1β, MCP-1, IL-6, TGF-β, CTGF, collagen-IV and α-SMA were analyzed by real-time PCR. Immunofluorescence staining of phospho-histone H3 (p-HH3) and Ki67 was performed to determine the stage of cell cycle G2/M arrest. Results The expression and activity of sEH increased in UUO group (P﹤0.05). Administration of sEHI inhibited activity of sEH and infiltration of inflammatory cell in tubular interstitial, as well as attenuated tubular damage and tubular interstitial fibrosis. Western blotting analysis revealed administration of sEHI inhibited up-regulated NF-κB p65 and down-regulated IκB in UUO group (P﹤0.05). Real-time PCR demonstrated that administration of sEHI obviously decreased the mRNA expression of cytokines and fibrosis markers, including of TNF-α, IL-1β, MCP-1, IL-6, TGF-β, CTGF, Collagen-IV, α-SMA (P﹤0.05). Immunofluorescence staining showed that there were much more p-HH3 and Ki67 double positive nuclear tubular epithelial cells and interstitial cells in UUO group, compared with Sham group (P﹤0.05). Administration of sEHI reduced the number of double positive nuclear cell only in tubular epithelial cells (P﹤0.05), but not in interstitial cells. Conclusions In UUO tubular interstitial fibrosis model, sEHI inhibits the activation of NF-κB pathway by down-regulating p65 and up-regulating IκB and ameliorates the infiltration of inflammatory cells. In addition, sEHI plays anti-fibrosis effect by moderating cell cycle G2/M arrest and reducing the excrete of pro-fibrosis factors of tubular epithelial cells.

Objective To investigate the role of the non-receptor tyrosine kinase c-Abl in high glucose-induced podocyte injury and its possible signal transduction pathway. Methods Differentiated mouse podocytes were exposed to different glucose concentration conditions in different time slots. Western blotting and immunofluorescence assay were used to measure c-Abl expression and distribution. c-Abl siRNA was transfected to block c-Abl expression. Then podocytes were divided into normal control group (5 mmol/L glucose), high permeability (25 mmol/L mannitol) group, high glucose group and high glucose + c-Abl siRNA group. The podocytes apoptosis was assessed by flow cytometry and Hoechst 33258 staining. The protein expression of c-Abl and p53 was detected by Western blotting. The distribution of c-Abl was observed by immunofluorescence. Co-immunoprecipitation assay was used to evaluate the interaction between c-Abl and p53. Results Compared with normal group, high glucose-induced podocytes had increased apoptosis (P＜0.05), and up-regulated c-Abl expression (P＜0.05) in time and concentration dependent manner. More c-Abl was distributed in the nuclei. Moreover, high glucose promoted the expression of p53 and the interaction of c-Abl and p53 (all P＜0.05). Compared with high glucose group, transfection of c-Abl siRNA restored high glucose-induced podocytes apoptosis (P＜0.05). The reduction of c-Abl and p53 expression, and the combination of c-Abl and p53 were also diminished in high glucose+c-Abl siRNA group (P＜0.05). There was no significant difference between normal control group and high permeability group (all P＞0.05). Conclusion During the process of high glucose-induced podocytes damage, c-Abl is an apoptosis factor, associated with p53 signaling pathway.

Objective To observe the effect of adenosine monophosphate activated protein kinase (AMPK) on attenuating inflammation in fibrosis induced by acute ischemia reperfusion injury (IRI) in mice. Methods Forty eight male C57BL/6 mice were randomly divided into four groups: sham operation group (sham group), IRI group, AMPK inhibitor+IRI group (AMPK/IRI group) and normal saline+IRI group (NS/IRI group), 12 mice each group. The mice with renal IRI were occluded for 30 min through clipping bilateral renal pedicle, then released renal perfusion. Mice in sham group were performed the separation of renal pedicle without clipping. Mice in AMPK/IRI group and NS/IRI group were respectively intraperitoneal injected AMPK inhibitor and normal saline before IRI. At the 2 d after operation, 6 randomly-selected mice from each group were blooded by extraction eyeball to detect BUN and Scr. The renal histopathological changes were observed through HE staining. The mRNA expression of IL-1β, IL-6 and TNF-α was detected by real time PCR, and the level of AMPK phosphorylation was detected by Western blotting. At the 14 d after operation, Collagen 1 (COL1), α-SMA and fibronectin (FN) were detected by immunofluorescence and Western blotting in 6 remained mice from each group. The degree of kidney fibrosis was observed through sirus red staining. Results Compared with those in sham group, tubular interstitial damage was aggravated (P＜0.05), BUN and Scr were increased (P＜0.05), the mRNA expression of IL-1β, IL-6 and TNF-α was increased at the 2 d after operation (all P＜0.05), and the level of AMPK phosphorylation was activated in IRI group and NS/IRI group (all P＜0.05); the degree of kidney fibrosis and the expression of COL1, α-SMA and FN were increased obviously at the 14 d (all P＜0.05). Compared with those in IRI group, in AMPK/IRI group tubular interstitial damage was aggravated (P＜0.05), BUN and Scr were increased (all P＜0.05), the mRNA expression of IL-1β, IL-6 and TNF-α was increased at the 2 d (all P＜0.05), and the level of AMPK phosphorylation was decreased (P＜0.05). Moreover, the degree of kidney fibrosis and the expression of COL1, α-SMA and FN were increased obviously at the 14 d in AMPK/IRI group (all P＜0.05). Conclusions AMPK can ameliorate the acute renal ischemia reperfusion injury induce fibrosis in mice, and the mechanism may be related to the decrease of inflammatory reaction.