Objective To explore the indications of detecting hepatitis C virus(HCV)-antigen in kidney tissue from infected patients with glomerulonephritis(GN). Methods Twenty-one patients with various GN were found to be HCV-antibody positive (7 serum HCV-RNA positive simultaneously), at the time of renal biopsy, from January 2005 to April 2008 in our hospital. Murine monoclonal antibody against NS3 protein was employed to detect HCV-antigen by immunohistochemistry. In addition, comprehensive investigations of these 21 patients were undertaken including an evaluation of their clinical, biochemical, virological and immunological parameters. Results HCV-NS3 antigen was detected in six (6/21) HCV-antibody positive patients and four out of the seven were serum HCV-RNA positive (4/7 in HCV-RNA positive, 57.1%). HCV immunoreactive deposits mainly displayed along glomerular capillary walls and/or mesangial region. MPGN was the most common type of GN accounting for 50% of HCV-NS3 immunoreactive staining patients. It seemed worth emphasizing that the mean age, urinary protein loss were significantly higher in HCV-NS3 positive patients than in those negative（P＝0.01）, while serum C3 level was significantly lower in the former group（P＝0.01）. Conclusion Detection of HCV-antigen in kidney tissue can not only provide a direct evidence for the diagnosis of HCV-associated GN, but also give an indication of pathogenic role of HCV in the renal damage.

Objective To compare the efficacy and safety of intermittent patient-initiated single-dose antibiotic prophylaxis and continuous antibiotic prophylaxis for the prevention of recurrent urinary tract infection (UTI) in postmenopausal women. Methods A randomized controlled clinical trial was conducted for the prevention of recurrent urinary tract infection. Single dose of antibiotic was given every night in continuous antibiotic prophylaxis group and every time after exposure to conditions predisposed to UTI in intermittent antibiotic prophylaxis group. The duration of prevention was 12 months in both groups. Results The effective rates of intermittent antibiotic prophylaxis and continuous antibiotic prophylaxis were 71.0% and 81.8% respectively(P>0.05). The incidence of gastrointestinal adverse reaction in intermittent antibiotic prophylaxis group was significantly lower than that in continuous antibiotic prophylaxis group (7.7% vs 28.6%,P<0.05). Conclusions Compared with continuous antibiotic prophylaxis, intermittent patient-initiated single-dose antibiotic prophylaxis is a better prophylaxis with less gastrointestinal adverse reactions for the prevention of recurrent urinary tract infection in postmenopausal women.

Objective To evaluate the characteristics of patients on long-term peritoneal dialysis (PD). Methods Patients who started PD since 1994 and received PD for at least one year were included in this study. According to dialysis duration, patients were divided into two groups. Group A (long-term) was defined as patients survived on PD for more than 5 years. Group B (short-term) was defined as patients who died or switched to hemodialysis within less than 5 years. Demography, biochemical indexes, dialysis prescription and adequacy were compared between two groups. Results There were 68 patients in group A and 98 patients in group B. Mean followed-up period of group A and B was (84.80±19.42) months and (27.25±12.31) months, respectively. Younger, fewer episodes of diabetic comorbidity (group A 3/68 vs group B 18/98, P <0.05) and coronary heart disease (group A 6/68 vs group B 22/98, P<0.05) were found in group A. Compared to group B, the level of serum albumin at the beginning of PD was much higher in group A[(35.56±4.74) g/L vs (33.69±5.45) g/L, P<0.01). The levels of blood sugar, TC, TG, hemoglobin, calcium, phosphate and iPTH were not significantly different between two groups. Estimated GFR, renal Kt/V and renal Ccr at the beginning of dialysis were much higher in group A, however there was no significant difference in urinary volume between two groups. Both estimated GFR and urinary volume decreased more slowly in group A compared to group B. Peritonitis mobidity was lower in group A (1/81.22 months vs 1/29.03 months, P<0.01). Conclusions In comparison to short-term survivors, long-term PD patients are characterized by being younger, less diabetic and coronary heart disease, fewer episodes of peritonitis, higher level of serum albumin, higher estimated GFR and less loss of residual renal function.

Objective To investigate the prevalence, awareness and risk factors of chronic kidney disease (CKD) among community adult population in Shanghai, China, in order to provide early diagnosis and treatment of CKD, and informations for national health policy makers. Methods Two thousand five hundred and ninety six residents (≥18 years old) were randomly selected from community population in Changning district of Shanghai, China. They were interviewed and tested for albuminuria -morning spot urine albumin to creatinine ratio [ACR, abnormal: ≥17 mg/g (male), ≥25 mg/g (female)], reduced renal function-estimated GFR by abbreviated MDRD equation [abnormal: <60 ml&#8226;min-1&#8226;(1.73 m2)-1] and hematuria-morning spot urine dipstick confirmed by urine microscopy. The associations among demographic characteristics, healthy characteristics (e.g. diabetes and hypertension) and indicators of kidney damage were examined. The investigators and neighborhood committee were well trained. Those who had semi-quantitative positive were detected again by albuminuria-morning spot urine albumin to creatinine ratio after three months. Results Two thousand five hundred and fifty four residents with complete data were enrolled in the study. Albuminuria was detected in 6.3% of subjects, reduced renal function in 5.8%, hematuria in 1.2%. Approximately 11.8% of these subjects had at least one indicator of kidney damage. The awareness rate of CKD was 8.2%. The Logistic regression model showed that hyperuricemia, nephrolithiasis, anemia, diabetes, central obesity, hypertension and age contributed to the development of CKD. Conclusions The prevalence of CKD in community adult population in Shanghai is 11.8%, And the awareness rate of CKD is 8.2%. Hyperuricemia, nephrolithiasis, anemia, diabetes, central obesity, hypertension and age are risk factors of CKD.

Objective To investigate the change of lipoxin A4 (LXA4), leukotriene B4 (LTB4) in blood and urine and leukocyte 15-lipoxygenase(15-LO) of the children with acute poststreptococcal glomerulonephritis (APSGN) and to evaluate its significance. Methods Blood and urinary levels of LXA4 and LTB4 were measured with ELISA within 3 days (acute phase), 10 to 14 days (early resolution phase) and 6 to 8 weeks (late resolution phase) respectively after onset of APSGN in 22 patients. In 8 children with APSGN, expression level of leukocyte 15-LO mRNA was examined with RT-PCR. Leukocyte LTB4 synthesis was assessed with ELISA. Chemotactic effect of LTB4, LXA4 and 15-S-hydroxyeicosatetraenoic acid (15-S-HETE) on neutrophils was determined by in vitro chemotaxis assay. Twenty-two healthy children were served as control. Results Blood and urinary levels of LXA4 and leukocyte 15-LO mRNA were up-regulated in acute phase, further increased in early resolution phase, and decreased in late resolution phase of APSGN, which were still higher than those in the controls (P<0.01). Blood and urinary levels of LTB4 were increased in acute phase (P<0.01) and then were decreased in early resolution phase and late resolution phase of APSGN, which were still higher than those in the controls (P<0.01). Administration of 15-S-HETE or LXA4 in vitro inhibited LTB4-induced chemotactic effect on neutrophils of the patients, and inhibited the production of leukocyte LTB4. Conclusions Changes of blood and urinary levels of LXA4 and LTB4 in early resolution phase of APSGN are contrary. 15-S-HETE and LXA4 may play a role in anti-inflammation and resolution of APSGN via inhibiting LTB4.

Objectives To detect the effects of P-selectin on deep venous thrombosis (DVT) in nephrotic syndrome (NS), and to evaluate the molecular magnetic resonance imaging (MRI) with a P-selectin targeted contrast agent in diagnosis of thrombosis in the early phase. Methods (1) Forty-one patients with NS hospitalized in our department from 2005 to 2006 were enrolled in this study. They were assigned into DVT group and non-DVT group according to lower limbs radionuclide imaging (RNV) with 99mTc MAA. Blood P-selectin level was measured by ELISA method. (2) P-selectin was detected both in injured vein and blood immediately, 1 h and 3 h after the dog DVT model was established. (3) The P-selectin-targeted contrast agent was developed by conjugating anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb) which was prepared by our lab. The potential of this contrast agent used in vitro molecular imaging experiment as well as in vivo experiment in dog DVT model was investigated. Results (1) Blood P-selectin level was elevated in patients with NS. It was much higher in DVT group than that in non-DVT group. (2) Blood P-selectin level was also elevated in DVT dogs and P-selectin expressed immediately in tunica intima of injured vein and subsequently in thrombus after the model established. (3) Mural thrombus showed higher signal visualization than surrounding muscle in 30 min after contrast agent injection. These enhanced signals exhibited P-selectin specificity and persisted from the initiation of intima lesions to 3 h after development of thrombosis. There was signficant Differences in contrast-to-noise ratio (CNR) of the experiment group and the control group (11.50±2.32 vs 2.71±0.86, P<0.01). The same results were derived from 30 min to 1 h after contrast agent being injected in distal to heart part of the injured vessel, and the signal decreased 24 h later. Differences in CNR of the experiment group and the control group were also statistically significant (10.40±2.15 vs 1.93±0.57, P<0.01). Moreover, the contrast agent did not affect the vital signs of the dog. The function of the heart, lung, liver and kidney functions remained normal after contrast administration. Conclusions P-selectin-targeted new MR contrast can be used to early locate thrombus in vivo in an early stage, which does not compromise the function of the important organs. It may become a new method for early diagnosis of thrombosis.

Objective To evaluate the effects of 1，25（OH）2D3 on podocyte apoptosis in kidney of puromycin aminonucleoside nephropathy (PAN) rats. Methods Seventy-two male Sprague-Dawley rats were randomly divided into three groups: PAN model group(PAN), 1，25（OH）2D3 treated group(T, 0.2 μg·kg-1·d-1 by gavages) and normal control group(NC). PAN rat model was constructed by a single intravenous injection of 100 mg/kg body weight. Renal function and 24-hour urinary protein were measured at day 3, 7, 14, 21 after PAN injection. The renal tissue morphology was observed by light and electron microscope. Podocyte apoptosis was evaluated by TUNEL. Protein expressions of nephrin, TGF-β1 and p-Smad2/3 were examined by immunofluorescence, immunohistochemistry and Western blot, respectively. Results (1)The levels of serum creatinine, BUN and 24-h urinary protein [（20.26±4.87） mg vs（1.01±0.41） mg at day 7, P <0.01] were significantly higher and the number of glomerular podocyte was significantly lower [(10.9±4.2)/glomerular volume vs (31.9±6.2)/glomerular volume at day 14, P＜0.01] in PAN group compared with NC group. T group rats had less urinary protein excretion[（9.95±3.82） mg/24 h, P<0.01] and more glomerular podocytes compared with PAN group. (2) Distribution of nephrin expression was changed from linear to granular pattern in PAN rats on day 7, nephrin mRNA and protein expressions were markedly decreased（P<0.01）, while the number of apoptotic podocyte was increased in PAN group（P<0.01）. However, higher nephrin expression and less apoptotic podocytes were found in T group (P<0.01). (3) Compared with NC group, the mRNA and protein expression of TGF-β1 and p-Smad2/3 were higher in PAN group（P<0.01）, while 1,25(OH)2D3 treatment abrogated PAN-induced changes in the expression of TGF-β1 and p-Smad2/3（P<0.01）. Conclusions 1,25(OH)2D3 can significantly suppress PAN-induced podocyte apoptosis and ameliorate proteinnuria. The beneficial effect of 1,25(OH)2D3 on podocyte may contribute to direct suppression of TGF-β signaling.

Objective To clarify why accelarated atheroslcerosis is complicated in chronic kidney disease patients, and to investigate whether endoplasmic reticulum (ER) stress can be observed in acetylated low density lipoprotein (ACLDL)-induced apoptosis in THP-1 macrophages differentiated by 160 nmol/L PMA for five days. Methods Hoechst 33258 stain and caspase 3,7 assay were used to detect apoptosis. Oil red O was used to examine the lipid droplet. High performance liquid chromatography was used to measure intracellular free cholesterol(FC) and cholesterol ester(CE). Western blot was applied to demonstrate the protein level of acyl-coenzyme A cholesterol acyltransferase(ACAT)1, growth arrest and DNA damage(CHOP) and Bcl-2. Real-time PCR was used to detect the changes of mRNAs. Results ACLDL could induce THP-1 macrophages apoptosis in time-and dose-dependent manner. After exposure to 100 mg/L ACLDL for 24 hours, the level of free cholesterol and cholesterol ester mass had a significant increment by 1.5- and 2.4-fold respectively (P<0.01). CHOP increased and Bcl-2 decreased both in protein and mRNA levels. ACLDL loading also resulted in an increase of ACAT1 protein without any change in mRNA level. Conclusion In THP-1 macrophages foam cell, apoptosis can be induced by ACLDL accompanied by ER stress pathway activation.

Objective To investigate whether aldosterone infusion induces glomerular or podocyte injury in rats and to evaluate the effects of eplerenoen(EPL), amlodipine(CCB) and telmisartan(ARB) on aldosterone- induced injury. Methods Thirty male Sprague-Dawley rats were divided into 5 groups: control, subcutaneous infusion of aldosterone (1.5 μg/h, ALD group) and aldosterone infusion plus eplerenone (100 mg·kg-1·d-1, EPL group), amlodipine(10 mg·kg-1·d-1, CCB group), telmisartan (3 mg·kg-1·d-1, ARB group), respectively. Systolic blood pressure(SBP) and urinary albumin excretion ratio(UAER) were measured at day 0, 7, 14, 21, 28. Blood samples were harvested to detect plasma angiotensinⅡ, plasma aldosterone, serum sodium, serum potassium and serum creatinine at day 28. Glomerular damge was quantified by morphological glomerular injury score (GIS). Immunohistochemistry and RT-PCR were performed to evaluate podocyte lesion, and apoptosis ratio of podocyte(ARP) in a glomerular cross section was analyzed by TUNEL. Results ALD infusion progressively increased SBP and UAER compared with CTL（P<0.01）. SBP was significantly reduced in EPL, CCB or ARB-treated animals, meanwhile, UAER was decreased in EPL and ARB group, but not in CCB group. The ALD-infused rats exibited hypernatremia and hypopotassaemia, which were blocked by EPL adminstration but not by CCB or ARB treatment. ARB group had a significant increase in plasma angiotensinⅡcompared with ALD, CCB and EPL groups（P<0.01）. The ALD-infused animals developed hyperaldosteronemia compared with CTL, but with no difference of plasma aldosterone among ALD, EPL, CCB and ARB-treated rats. Treatment with EPL prevented an increase of GIS and ARP compared with CCB and ARB（P <0.05, P<0.01）. Protein and mRNA expression of nephrin was up-regulated in ALD group（P<0.01）, but was significantly prevented by EPL treatment（P<0.01）, whereas CCB and ARB therapy had no such effect. Conclusion ALD infusion significantly induces glomerular and podocyte injury which is blocked by EPL but not by CCB or ARB independently on systemic hemodynamics.

Objective To investigate the effect of all-trans retinoic acid (atRA) on the renin-angiotensin system (RAS) in 5/6 renal ablation model. Methods AtRA was administered to 5/6 renal ablation rats by three dosages: 5 mg·kg-1·d-1 (n=8), 10 mg·kg-1·d-1 (n=8) and 20 mg·kg-1·d-1 (n=8) and vehicle (vehicle group, n=8) for 10 weeks. Healthy rats consisted of sham-operation group(n=8). The level of renin and angiotensinⅡin renal tissues were measured by radioimmunoassary. The level of angiotensin type 1 receptor(AT1R) in remnant renal cortex was measured by Western blot. The mRNA expression levels of two subunits of activative protein 1(AP-1), c-jun and c-fos was quantitated by real-time PCR. Results After 10 weeks of atRA treatment by gavarge, artery blood pressure decreased (P<0.05). AtRA reduced the levels of renin (P<0.05) and angiotensinⅡ（P<0.05) in kidney and down-regulated the expression of AT1R protein in renal cortex. Larger dose of atRA (20 mg·kg-1·d-1) performed higher activity in inhibiting renin and AT1R. Compared with vehicle group, atRA could significantly inhibit the expression of renal c-jun and c-fos mRNA(P<0.05). Conclusion atRA can decrease the over-expression of main components of RAS.

Objective To investigate the effects of pravastation intervention on tumor necrosis factor（TNF）-α-induced ossific calcification in human umbilical artery smooth muscle cells (hUASMCs). Methods hUASMCs were cultured by tissue explant in vitro. hUASMC were treated with TNF-α 50 μg/L and pravastatin of three different concentrations. The calcium deposition was determined by O-cresolphthalein complexone method. The mRNA expression of BAP and OPN was determined by real time-PCR. The protein expression of BAP, OPN and BMP-2 was determined by Western blotting. Results Pravastatin inhibited the proliferation of hUASMC (r=－0.946, P<0.01) and decreased the cell calcium deposition (r=－0.973, P<0.01) in a dose-dependent manner. Pravastatin down-regulated the expression of BAP, OPN and BMP-2 induced by TNF-α in a dose-dependent manner (mRNA, r=－0.972, P<0.01; BAP protein, r=－0.820, P<0.01; OPN protein, r=－0.972, P<0.01; BMP-2 protein, r=－0.928, P<0.01). Conclusion Pravastatin can inhibit the proliferation of hUASMC, decrease the cell calcium deposition and inhibit the ossific calcification of hUASMC induced by TNF-α.