Objective To test the hypothesis whether the angiotensin receptor blocker (ARB)irbesartan can slow the decline of residual renal function in patients with end-stage renal failure treated with peritoneal dialysis. Methods Forty-eight ESRD patients undergoing regular CAPD were randomly assigned to irbesartan (300 mg/d, n=24) or control group (n=20). Conventional antihypertensive treatment was continued in all patients to achieve the target BP in both groups of 120～135/70～85 mm Hg. Results Over 12 months, blood pressure (BP) reduction was similar in the irbesartan and control groups. The residual eGFR in both groups were declined. In irbesartan group, the initial decline in residual eGFR during the first 6 months was steeper than the sustained decline during the second 6 months. At the end of the study, the value of residual eGFR in irbesartan group was greater than that in control group [(1.68±1.01) vs (1.04±0.76) ml/min, P< 0.05]. Irbesartan could significantly slow the progressive declining of residual renal function. Conclusion Irbesartan may reduce the rate of decline of residual renal function in patients with regular peritoneal dialysis

Objectives To determine the incidence, the constitution of causes and the prognosis of acute kidney injury (AKI) among hospitalized patients in a tertiary hospital, and to evaluate the impact of AKI on hospital cost and length of stay (LOS). Methods Patients who were admitted in Zhongshan Hospital, Fudan University from September 1st 2004 to August 31st 2005 were involved. After checking the computer-based data on kidney function, patients with acute kidney injury were picked out and further history reviews were demanded to get the information of clinical characteristics, prognosis, severity of kidney injury and the causes of AKI. Results There were 37 365 admissions during the study period and 1263 met with the diagnostic criteria of acute kidney injury(AKI). The overall incidence of AKI was 3.38%. In-hospital mortality was 1.52% in all discharges while 18.57% in patients with AKI. The multivariable-adjust OR for death associated with AKI was 10.08 (P<0.01). The results of logistic regression analysis suggested that old age and the elevation percentage of serum creatinine were the risk factors of death among AKI patients. Conclusions Acute kidney injury is prevalent in hospitalized patients. A slight elevation of serum creatinine is associated with significantly increased mortality, LOS and hospital cost. Moreover, outcomes are related directly to the severity of acute kidney injury, which characterized by elevation percentage of serum creatinine

Objective To investigate the utility of cytodiagnostic urinalysis in detecting renal pathological changes in acute renal failure. Methods Fresh morning urine specimens of 50 patients with acute renal failure (ARF) were collected at the day of renal biopsy. The pathological diagnosis was made by light microscopy, immunofluorescence and electron microscopy. They were roughly classified into proliferative glomerular disease, non-proliferative glomerular disease and tubulointerstitial lesions. Urinary sediment was examined by two experts with phase-contrast microscopy, who did not know the pathological result and clinical information. Formed elements in the urine sediment included erythrocytes, all kinds of karyotes and casts. The cytodiagnostic urinalysis was classified into 3 types. Type 1: dysmorphic erythrocytes, erythrocytic cast, phagocyte (engulf erythrocytes), monocyte or coenocyte, with or without large amount of proteinuria. Type 2: hyline and granular casts with karyotes, few erythrocytes or karyotes , large amount of proteinuria. Type 3: hyline and granular casts with karyotes, less proteinuria. Results In 33 patiens with proliferative glomerular disease, cytodiagnostic urinalysis of type 1 was found in 30 cases (91%). Eight of 9 cases of non-proliferative glomerular disease presented cytodiagnostic urinalysis of type 2. Cytodiagnostic urinalysis of type 3 was found in 5 of 8 cases of tubulointerstitial lesions. Conclusion Cytodiagnostic urinalysis combined with proteinuria quantification is a non-invasive, cheap, convenient method to reflex the severity and region of renal injury in ARF

Objective To analyze the clinical and pathologic characteristics of membranous nephropathy (MN) associated with primary Sjogren’s syndrome (pSS). Method The clinical and pathologic data from 17 patients, with 11 female, 6 male, and a mean age of（47.3±17.3）（24～72） years, suffered from pSS and MN in Peking Union Medical College Hospital from May 2001 to May 2006 were analyzed. Results All the patients had edema and proteinuria including 13 nephrotic syndrome. According to the findings of light microscopy, immunofluorescens and elctronic microscopy, 17 cases were divided into pure MN group and atypic MN group. In eight pure MN patients, no significant mesangial abnormalities were observed and electron microscopy only showed subepithelial and intra-membranous electron-dense deposits. While in atypic MN group, mesangial proliferation and positive C1q were found under light and immunofluorescens microscopy. Electron microscopy showed electron-dense deposits not only in subepithelial and intra-membrane, but also in mesangial areas. Two patients received renal rebiopsy, one patient transformed from MN phase I into atypic MN after 8 years, another atypic MN patients transformed into lupus nephritis after 4 years. Conclusion Membranous nephropathy associated with primary Sjogren’s syndrome is quite common in primary Sjogren’s syndrome patients with proteinuria

Objective To investigate the association of interleukin-10(IL-10) gene promoter －3575 and －2763 polymorphism with systemic lupus erythematosus (SLE) and lupus nephritis（LN）of Han nationality people in Southern China. Methods One hundred and three patients (13 male and 90 female) with SLE， including 62 with LN fulfilled the American College of Rheumatology 1982 revised criteria for SLE and 110 healthy ethnically matched controls (21 male and 89 female) were enrolled. All of the subjects were from Southern China and consented to participate in the study. Blood samples for DNA extraction from all subjects were collected in EDTA tube. Genomic DNA was extracted according to the standard isolation procedures. IL-10 promoter －3575 and －2763 polymorphisms were typed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results IL-10 promoter －3575 polymorphism was found widely in above people. All genotype frequencies of IL-10 promoter －3575 were in Hardy-Weinberg equilibrium. Compared with the healthy controls， the frequencies of TT genotype and T allele of IL-10 promoter －3575 were significantly lower in the patients (P<0.05)， but the frequencies of AA genotype， AT genotype and phenotype were not significantly different between patients and controls (P>0.05). There were significant differences of IL-10 promoter －3575 TT genotype， allele and phenotype frequencies between female SLE patients and female controls (P<0.05). There were no significant differences of IL-10 promoter －3575 genotype， allele and phenotype frequencies between the patients with LN and the controls (P>0.05). No IL-10 promoter -2763 polymorphism was found and the genotypes were AA genotype in all patients and controls. Conclusion IL-10 promoter －3575 polymorphism appears to be associated with susceptibility to SLE but not to LN patients in Southern China

Objective To investigate the relationship of mannose-binding protein(MBP) gene polymorphism to various patterns of glomerular immune deposits in IgA nephropathy patients of Uygur nationality in Xinjiang. Methods Sixty-eight patients with biopsy-proven IgA nephropathy were identified from renal disease database. Two hundred healthy donors served as normal controls. MBP codon 54 gene polymorphism was detected by PCR-RFLP. MBP genotype and allele frequency were compared between different patterns of glomerular immune deposits in IgA nephropathy patients and normal controls. Results Distribution of MBP codon 54 gene polymorphism showed no signficant difference between Uygur IgA nephropathy patients and Uygur normal controls. Distribution of MBP gene polymorphism in Uygur IgAN patients with different patterns of immune deposits showed significant difference. The genotype frequency of GAC heterozygote was significantly higher in group with glomerular IgA, IgG, IgM, C3 and C1q deposits in the mesangium as compared to that in group with isolated IgA and C3 deposits (44.7％ vs 20.0％), and as well as the GAC allele frepuency(0.303 vs 0.133). Conclusions Immunopathological polymorphism of Uygur IgAN is influenced by genetic context. The GAC heterozygote of MBP gene codon 54 may contribute to different patterns of glomerular immune deposits in Uygur IgAN patients

Objective To explore the inhibitory effect of mizoribine(MZ) on rat mesangial cell proliferation and its influence on CKI p27kip1 expression in vitro. Methods Primary cultured rat mesangial cells were divided into 24 hr FCS free group, 20% FCS group, and 20% FCS+ MZ(0.5～50 mg/L)group. Cell numbers were detected by MTT. S phase entry was measured by BrdU labeling. Cell cycle profiles were determined by flow cytometric analysis. The expression of p27kip1 protein was detected by Western blotting. Results MZ inhibited FCS-stimulated mesangial cell proliferation in a dose-dependent manner. Cell cycle analysis and BrdU labeling showed that MZ prevented FCS-stimulated mesangial cells from entering S phase [(12.22±1.22)％ vs (23.19±0.38)％, P＜0.05]. The expression of p27kip1 protein was down-regulated by FCS, which was significantly counteracted by MZ. Conclusion MZ can inhibit mesangial cell proliferation effectively in vitro, which is at least partly mediated through up-regulating the expression of p27kip1 protein

Objective To investigate the expression of Par-3 in epithelial-mesenchymal transition (EMT) of TGF-β1-stimulated NRK52E cells and the effect of over-expression of Par-3 by gene transfection on EMT. Methods NRK52E cells were grown in DMEM medium supplemented by 10% fetal bovine serum. NRK52E cells were cultured in free serum medium for 24 h, then were stimulated by TGF-β1 (10 μg/L). The expression of E-cadherin, α-SMA, Par-3 mRNA and protein were detected by RT-PCR, Western blot and immunofluorescence, respectively. NRK52E cells were transiently transfected with 1 μg pKH3-HA-Par-3 DNA by Lipofectamine 2000, then the expression of E-cadherin， α-SMA and Par-3 protein were detected by Western blot. Empty pKH3 vector was used as negative control. Results The expression of E-cadherin mRNA and protein were markedly decreased in NRK52E cells induced by TGF-β1, and the expression of α-SMA mRNA and protein were dramatically increased. Western blot analysis demonstrated that the protein level of Par-3 was progressively reduced in a time-dependent manner in response to TGF-β1 treatment in NRK52E cells, which was consistent with immunofluorescence staining results. However, TGF-β1 treatment did not affect the mRNA level of Par-3. Forced expression of exogenous Par-3 led to a severe blockage of TGF-β1-induced E-cadherin suppression and α-SMA induction. Conclusion The expression of Par-3 protein is down-regulated in NRK52E cells stimulated by TGF-β1 and overexpression of Par-3 can suppress EMT induced by TGF-β1, which suggests a protective role for Par-3 in TGF-β1-induced tubular EMT and renal fibrosis

Objective To explore the effects of pretreatment with cobalt chloride （CoCl2）or normbaric hypoxia（8％O2）on ischemia reperfusion injury（IRI）of the kidney in mice and its relationship to hypoxia inducible factor 1α（HIF-1α） and heme oxygenase1（HO-1）． Methods Thirty-five C57BL/6N male mice were randomly divided into 7 groups：control group， CoCl2 group， 8％O2 group， sham operation group， ischemia reperfusion（IR） group， CoCl2＋IR group and 8％O2＋IR group． IRI was induced in mice by clamping both renal pedicles for 30 min． The expression of HIF-1α and HO-1 were detected by Western blot． Renal function was reflected by blood urea nitrogen（BUN）and serum creatinine（Scr）． Morphologic changes were evaluated under light microscopy． Apoptosis in the kidney was detected by TUNEL staining． The expression of vimentin， a marker of tubulointerstitial damage, was detected by immunohistochemistry． Results Compared with sham group, elevation of BUN（65.8±2.6 vs 13.6±0.7， P<0.01），Scr（229.5±11.2 vs 6.5±0.8， P<0.01） and morphological injury after the ischemic insult were found in IR group. Pretreatment with CoCl2 and 8％O2 induced significant functional improvement（CoCl2 treatment：
BUN 35.2±12.2 vs 65.8±2.6, Scr 34±9.7 vs 229.5±11.2; 8％O2 treatment：BUN 31.8±9.1 vs 65.8±2.6, Scr 41.6±10.6 vs 229.5±11.2 respectively， P<0.01）associated with amelioration of tubulointerstital damage. In the kidneys of mice treated with CoCl2 and 8％O2，protein levels of HIF-1α and HO-1 were up-regulated significantly． Conclusion Pretreatment with CoCl2 or 8%O2 attenuates IRI of the kidney in mice mediated by activation of HIF-1α and expression of HO-1

Objective To observe the effect of sTie-2-Fc on TNF-α-induced angiogenesis of human omental tissue microvascular endothelial cells（HOTMEC）and explore the mechanism of angiogenesis induced by TNF-α. Methods HOTMEC was suspended in complete medium as control group and complete medium with TNF-α or TNF-α plus sTie-2-Fc or sTie-2-Fc only as experiment groups respectively. Then the capability of tube formation in Matrigel and migration in transwell plate as well as the permeability change to FITC labeled BSA of HOTMEC were observed. Results HOTMEC showed a typical cobblestone growth pattern and immunocytochemistry staining for Ⅷ factor was positive. As compared to the control, TNF-α promoted tube formation [（70±7） vs（17±4）tube/4 fields, P<0.05] and migration[（198±12） vs(38±7) cell/HP] of HOTMEC, meanwhile, such effects could be inhibited by sTie-2-Fc [（40±6）tube/4 fields, (76±11) cell/HP, P<0.05]. TNF-α could also enhance the permeability of HOTMEC, which could not be inhibited by sTie-2-Fc. Conclusion Angiopoietin-Tie-2 may contribute to angiogenesis in peritoneum by promoting tube formation and migration of HOTMEC in long-term PD patients

Objective To evaluate the effect of angiotensin Ⅱ (AngⅡ) infusion on the expression of angiotensin converting enzyme 2 (ACE2) in rat kidney and its implication in AngⅡ-induced kidney damage. Methods Eighteen male SD rats were randomly assigned to receive either normal saline or AngⅡ (400 ng&#8226;kg-1&#8226;min-1) by osmotic mini-pump, or to be used as normal controls. After the systolic blood pressure was measured, the 24 h urine sample was collected for detection of proteinuria at day 7, 14, 21, 28. Animals were sacrificed at day 28. Serum creatinine and renal pathological changes were observed. Renal nuclear factor (NF)-κB binding activity was evaluated by electrophoretic mobility shift assay (EMSA). Expression of ACE2 mRNA and protein was analyzed by RT-PCR, Western blot, and immunohistochemical staining. Results (1) AngⅡ-infused rats developed significant hypertension associated with marked proteinuria. At day 28, AngⅡ infusion induced glomerular mesangial proliferation, tubuloepithelial cell damage and inflammatory cell infiltration. (2) ACE2 was present in tubuloepithelial cell, especially in the brush border of proximal convoluted tubular cell. Renal expression of ACE2 mRNA and protein decreased dramatically in AngⅡ-infused rats at day 28 (P<0.05). Simultaneously, renal NF-κB binding activity increased markedly (P<0.05), and significantly negative correlation was found between the expression of ACE2 and NF-κB binding activity (r=-0.64, P<0.01). Conclusion The decrease of renal ACE2 expression may play a critical role in the pathogenesis of AngⅡ-induced kidney damage