Objective    To explore the impact of gender on the clinicopathological features of patients with primary IgA nephropathy (IgAN).    Methods    All patients with IgAN who were biopsy-proven in The First Affiliated Hospital, Sun Yat-sen University from January 2006 to December 2011 were divided into two groups by gender: male group and female group. The clinical manifestations and pathological features of two groups were retrospectively investigated and compared.     Results    A total of 1512 primary IgAN patients were enrolled in the study, and the ratio of male to female was 1∶1.16, with a median age of 32(26, 39) years old at biopsy. Compared to female patients, male patients with IgAN exhibited more severe clinical manifestations including worse renal function, greater urinary protein excretion, and more frequent occurrence of hypertension, hypertriglyceridemia and hyperuricemia. Besides, male patients had worse histological lesions, including more severe segmental sclerosis, tubular-atrophy/interstitial fibrosis and interstitial infiltration. For female patients, hematuria,  including gross and microscopic hematuria, was more frequent.    Conclusion    Male patients with IgAN were with worse clinicopathological changes than those of female.

Objective    To investigate the clinical features and treatment of the end stage renal disease (ESRD) patients in Gansu province.    Methods    Based on the Chinese national renal data system, the investigation and analysis were made on the epidemiological literature of ESRD patients in 22 hospitals of Gansu from 2012 to 2013 by retrospective investigation.    Results    (1) In Gansu, the number of living ESRD patients was 4379, the point prevalence rate of ESRD was 169.6 per million. Their average age was (47.46±15.57) years, 30 to 59 years old patients accounted for 70.0%, and the male-female ratio was 1:1.15. The prevalence rate was higher in less-educated population and manual laborers. (2) As the leading cause of ESRD, chronic glomerulonephritis accounted for 43.0%, followed by diabetic nephropathy (31.0%), hypertensive nephropathy (11.0%) and allergic diseases (6.9%). (3) The current treatment of ESRD: 51.2% of the patients  received hemodialysis, 4.4% received peritoneal dialysis, 1.1% received renal transplantation, 32.2% received no treatment, and 11.1% died. (4) The causes of patients not taking dialytic treatments: economic reasons accounted for 61.0%, lack of blood dialytic conditions accounted for 24.0%, patients ceasing treatment accounted for 3.1%, family factors accounted for 2.3%, religious reasons accounted for 1.8%, other reasons accounted for 7.8%. Conclusions  The point prevalence rate of ESRD in Gansu was 169.6 per million. 30 to 59 years old patients were the main population. The major cause of ESRD was chronic glomerulonephritis, followed by diabetic nephropathy and hypertensive nephropathy. 32.2% of ESRD patients did not receive any renal replacement therapy, which was caused mainly by economic difficulties and the lack of dialytic equipments.

Objective    To investigate the long-term outcomes of peritoneal dialysis (PD) patients with diabetes as a comorbid condition.    Methods    All diabetic patients who commenced PD between January 1, 1995 and June 30, 2012 at Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine were included in the present study. Patients were divided into diabetic kidney disease group (DKD group) and non-diabetic kidney disease group (NDKD group) according to their diagnosis of primary renal disease at the initiation of PD. They were followed until death, cessation of PD, transferred to other centers or to the end of study (June 30, 2013). Outcomes were analyzed by Kaplan-Meier method. Cox proportional hazards models were utilized to determine the predictors of outcomes. Results    A total of 163 diabetic patients were enrolled in the study. Compared with patients in DKD group, patients in NDKD group had a significantly lower fasting plasma glucose, a higher serum C-reactive protein level, a higher normalized protein nitrogen appearance, a lower dialysate glucose exposure, a lower peritoneal creatinine clearance and were treated with lower dialysate dose (all P＜0.05). Kaplan-Meier analysis showed that patients in NDKD group had a worse patient survive compared to those in DKD group (log rank Chi-square=4.830, P=0.028). Patients in NDKD group had a marginally shorter peritonitis-free period (log rank Chi-square=3.297, P=0.069), however, there was no significant difference in technique survival between these two groups. Multivariate Cox regression analysis showed that older age (HR 1.047, 95%CI 1.022~1.073, P＜0.001) and cardiovascular disease comorbidity (HR 2.200, 95%CI 0.1.269~3.814, P=0.005) and diabetes as a comorbid condition (HR 1.806, 95%CI 1.003~3.158, P=0.038) were the independent predictors for increased mortality. While higher serum C-reactive protein level (HR 1.023, 95% CI 1.008~1.036, P=0.003) was the independent predictor for shorter peritonitis-free period.    Conclusion    PD patients with diabetes as a comorbid condition had a higher mortality compared to those with diabetic kidney disease, and closer monitoring and extra attention in the former subgroup of patients are therefore warranted.

Objective    To investigate the use of vascular access and complication incidence in patients undergoing maintenance hemodialysis in Tianjin.    Methods    Patients undergoing maintenance hemodialysis in the third level of first-class hospital in Tianjin were investigated. The investigate method was live interview. Two thousand six hundred and fifty-one cases were available. Basic data, age of dialysis, type of vascular access, age of vascular access and complications were recorded. The differences in clinic data and complications between patients using arteriovenous fistulas (AVF) and central venous catheter (CVC) as vascular access were compared.    Results    There were 2047 (77.22%) patients using AVF as vascular access, 559 (22.59%) patients using tunnel type central venous catheter, and 5 (0.19%) patients using arteriovenous graft (AVG) for maintenance hemodialysis. Most patients used temporary catheter as the first vascular access [2484(93.70%)]. Compared to AVF, CVC had high incidence of thrombosis and infection in the first four years (P=0.003).    Conclusions    AVF remains the first choice for maintenance hemodialysis. Most patients use AVF as their vascular access. The second preferred choice is CVC. The management of late chronic kidney disease should be enhanced to avoid the high usage of temporary catheter.

Objective    To assess the impact of 24-week intradialytic exercise on the nutritional status, muscle strength and cardiorespiratory endurance of maintenance hemodialysis (MHD) patients.    Methods    Forty nine clinically stable MHD patients from Beijing Bo'ai Hospital were enrolled into the study, among forty three patients [65.1% men, (60.2±10.6) years] completed the trial. For 24 consecutive weeks, all patients performed one or two sets of cycle intradialytic exercise program during the first 2 h of their three dialysis sessions per week, 20 min for each set. The parameters included  body mass index (BMI), albumin (Alb), total cholesterol (TC), cross-sectional area of triceps brachii, triceps skinfold and grip strength. Nineteen patients performed the symptom-limited treadmill exercise test (modified Bruce protocol) to measure peak oxygen uptake (VO_2peak), metabolic equivalents (METs), vital capacity and stress-test duration. Their the knee extensor muscle strength was also meadured with the isokinetic test.    Results    After 24 weeks of exercise, there were increased Alb level (42.1 g/L vs 41.3 g/L, P=0.016), improved grip strength (25.5 kg vs 23.9 kg, P=0.012), and increased stress-test duration (14.5 min vs 13.2 min, P=0.005) in MHD patients.    Conclusion    The intradialytic exercise partially improves the nutritional status, muscle strength and cardiorespiratory endurance of MHD patients.

Objective    To investigate the roles of microRNA-382 (miR-382) in the pathogenesis of renal tubulointerstitial fibrosis (TIF).    Methods    Human kidney epithelial cells  (HK2)transfected with miR-382 inhibitor (antagomiR-382) were used to examine the effect of miR-382 abundance on cell polarity, as well as to test the complementary relationship between miR-382 and its predicted target gene heat shock protein 60 (HSPD1), which was further verified by 3′-untranslated region luciferase assay and site-directed mutagenesis. The role of miR-382 played in the development of renal interstitial fibrosis and redox regulation was examined in a mouse unilateral ureteral obstruction (UUO) model.  Locked nucleic acid (LAN)-modified anti-miR-382 was intravenous delivered via tail vein 30 min prior to UUO, and repeated the dosage 24 h after the surgery.  For clinical verification, renal biopsy specimens from 12 IgA nephropathy (IgAN) patients were collected, 6  patients with moderate to severe TIF and 6 patients without TIF. The relative abundance of miR-382 and HSPD1 protein was analyzed by using in situ hybridization and immunohistochemistry.    Results    HSPD1 was confirmed to be a new, direct target gene of miR-382 by in vitro 3′-untranslated region luciferase assay and site-directed mutagenesis. The development of epithelial transition in HK2 cells was accompanied with up-regulation of miR-382 [(6.54±0.96) vs (1.12±0.26), P＜0.05].  Blocking the expression of miR-382 could reversed the progression of epithelial transition partially. In UUO mice the abundance of miR-382 was up-regulated [(6.89±2.47) vs (1.00±0.42), P＜0.01] while HSPD1 and Trx were down-regulated compared with the sham group. Down-regulation of miR-382 was associated with significant decrease in TIF, but increase in HSPD1 and thioredoxin protein compared with UUO group [HSPD1: (0.34±0.10) vs (0.14±0.05); Trx: (0.79±0.18) vs (0.36±0.16); all P＜0.05]. The expression of miR-382 was up-regulated and HSPD1 was significantly down-regulated in IgAN patients with TIF.    Conclusions    miR-382 play an important role in renal tubulointerstitial fibrosis in human and mice. HSPD1 is one of the target genes of miR-382. The down-regulation of HSPD1 and the decrease ability of anti-oxidative stress may be the important mechanism of miR-382 involved in renal tubulointerstitial fibrosis. 

Objective    To evaluate the effect of oxidative injury induced by peroxide oxidase on Klotho expression in mouse renal tubular epithelial cells (TCMK-1) and to explore the possible pathway.    Methods    TCMK-1 cells were exposed to H₂O₂ of different concentrations. Reactive oxygen species (ROS) was examined by flow cytometry. Cell viability was assessed by CCK-8. Cell apoptosis was evaluated by flow cytometry and Hoechst 33258 staining. The expression of Klotho, apoptosis-associated proteins and anti-oxidant enzymes were determined by Western blotting.    Results     Compared with control group, after H₂O₂ stimulating TCMK-1 cell, ROS was dramatically elevated (all P＜0.05) and the expression of anti-oxidant enzymes, SOD2 and CAT went down (all P＜0.05); the expression of Klotho was inhibited (all P＜0.05); cell viability of TCMK-1 cells was decreased (all P＜0.05) in a dose-dependent manner (0.3 to 0.9 mmol/L); cell apoptosis was significantly increased in TCMK-1 cells following the concentration of H₂O₂ (all P＜0.05); Bax/Bcl-2 and the phosphororation of JNK and p38 were obviously elevated in TCMK-1 by H₂O₂ induction (all P＜0.05).    Conclusion  Oxidative injuries induced by H₂O₂ significantly suppresses the expression of Klotho in TCMK-1 cells. And cell apoptosis was increased, p38 and JNK pathway was activated.

Objective    To explore the protective effect and mechanism of astaxanthin (AST) on the acute kidney injury induced by iohexol in rats.    Method    Thirty rats were randomly divided into five groups: control group (Ctrl); iohexol group (CM); astaxanthin group (AST, 100 mg/kg), low astaxanthin dose group (LAST+CM, 50 mg/kg) and high astaxanthin dose group (HAST+CM, 100 mg/kg), 6 in each group. The rats in AST, LAST+CM, HAST+CM groups were administrated with AST by oral gavages using an intubation needle for 10 consecutive days. The rats in Ctrl and CM groups rats in Ctrl, CM groups were given with dissolvant instead in equal volume. Except for the Ctrl and AST groups, on day 8, rats were given indomethacin, L-NAME and iohexol in their femoral vein under chloral hydrate anesthesia to build a contrast induced-nephropathy (CIN) model. At the end of the experiment (72 h after CIN induction), all rats were sacrificed. The Scr level, BUN level, renal histology, renal tissue activities in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), Glutathione (GSH) and level of malondialdehyde ( MDA ) were performed. Apoptosis of renal cells was detected by Bcl-2, Bax and Caspase-3 p17 with Western blot.    Results    Compared with Ctrl group, the levels of Scr, BUN were significantly increased in CM group (all P＜0.01); while compared with CM group, the indicators were decreased in treatment groups (P＜0.01). Renal tubular structure damage, medulla congestion, loss of brush border, vacuolar degeneration, apoptosis and proteinaceous casts were observed in the CM group, and the renal injury scores were higher compared with Ctrl group (P＜0.05), however, administrated with AST could significantly improve the changes (P＜0.05). Oxidative stress indicators showed that MDA level were increased while SOD, GPx, GSH activities were significantly decreased at CM group (all P＜0.05), and the indicators above were ameliorated in treatment groups (all P＜0.05). Western blot showed that the expression of Bcl-2 was down-regulated while the Bax, Caspase 3 p17 was up-regulated respectively at CM group (P＜0.05), while the HAST+CM group could prevent the changes.   Conclusions    Iohexol can results in oxidative stress increased in kidney, which activate Caspase-3 p17 signal path, down-regulated Bcl-2 expression, up-regulated Bax expression respectively, and lead to cell apoptosis. AST can ameliorate the changes, especially with high AST dose, which suggest that the possible protection mechanism is by ameliorating oxidative stress and inhibiting apoptosis pathways.

Objective    To investigate the role of endoplasmic reticulum stress in tubular epithelial cell apoptosis in chronic proteinuria rat model and the effect of lisinopril intervention. Methods    Adriamycin nephropathy was induced in male Wistar rats (n=12) by a single injection of adriamycin at 2 mg/kg body weight. Rats were then randomly assigned to model group or treatment group, to which distilled water or lisinopril were administered respectively for 12 weeks. Six normal rats serving as controls were administered distilled water. 24 h urine samples were collected at week 4, 8, 12 and the urine protein was measured. At the end of study, serum was obtained and physiological parameters (serum creatinine, urea, total protein and albumin) were measured. Renal tubular epithelial cell apoptosis was assessed by TUNEL. GRP78, CHOP protein expression in kidney was quantified by immunohistochemistry and Western blotting.    Results    Compared to control group rats, increased proteinuria was observed in model group rats at week 4, 8, 12 (P＜0.05). Lisinopril treatment attenuated urine protein excretion significantly (P＜0.05). At week 12, hypoalbuminemia was detected in model group rats (P＜0.05), whereas the condition was alleviated by lisinopril (P＜0.05). There were no significant differences of serum creatinine, urea and total protein in each group (P＞0.05). Compared to control group rats, increased TUNEL positive tubular epithelial cells and tubular GRP78 and CHOP expression were also observed in model group rats (P＜0.05); however, these conditions in the kidney were significantly decreased in treatment group (P＜0.05).    Conclusions    Endoplasmic reticulum stress may be involved in the process of tubular epithelial cell apoptosis induced by proteinuria. Lisinopril may attenuate tubular epithelial cell apoptosis through regulating this signal pathway.

Objective    To observe the effect of parathyroid hormone on transdifferentiation of human renal proximal tubular epithelial cell (HK-2), and to investigate the role of Wnt signaling pathway in this process.    Methods    The expression of α-SMA, E-cadherin mRNA and protein was detected by real-time PCR and Western blotting. After the induction of 10^-10 mol/L PTH for 48 h, the Wnt pathway associated gene expression profiling was detected by quantitative PCR-microarray. The expression of Wnt4 mRNA and protein under various concentrations of PTH or after exposed to 10^-10 mol/L PTH for different time was detected by real-time PCR and Western blotting. The overexpression and knock-down plasmids of Wnt4 were constructed and the expression of α-SMA, E-cadherin, Wnt4 mRNA and protein was detected by real-time PCR and western blotting after overexpression and knockdown of Wnt4.    Results    Compared with PTH group, the expression of α-SMA mRNA and protein in PTH+DKK1 group was significantly down-regulated, while E-cadherin mRNA and protein expression was significantly up-regulated (all P＜0.01). PTH treatment resulted in the up-regulation of 18 genes and down-regulation of 9 genes associated with Wnt pathway. Compared with control group, the expression of Wnt4 mRNA and protein increased markedly in PTH group (all P＜0.01). The expression of α-SMA mRNA and protein was significantly up-regulated and E-cadherin mRNA and protein expression was significantly down-regulated after overexpression of Wnt4 and PTH treatment (all P＜0.05), while the expression of α-SMA mRNA and protein was significantly down-regulted and E-cadherin mRNA and protein expression was significantly down-regulated after knockdown of Wnt4 and PTH treatment (all P＜0.05).    Conclusions    PTH-induced EMT in HK-2 cells is mediated by Wnt signal pathway, and Wnt4 might be a key gene during PTH-induced EMT.