To study the relationship between endog-enous digitalis-like substance (EDLS) and ch-ronic renal insuffieiency(CRI), using radioimmu-noassay (RIA)with digoxin kit, we measured serum level of EDLS in patients with CRI, patients on hemodialysis (HD) and renal tra-nsplant patients. The results suggest that serum level of EDLS is closely related with renal function. When renal function goes down, the level of EDLS increases. This suggest that EDLS may be involved in pathogensis of CRI. HD can decrease serum level of EDLS. When the graft is functioning, the serum level of EDLS is similar to that in haalthy controls. The cor-relation between ELLS and renal hypertension is not clear.

Objective To investigate the cardioprotective effect of losartan o n subtotal nephrectomy renal failure rats. Methods Renal failure rats were estab lished by subtotal nephrectomy, and then divided into RF group with subtotal nep hrectomy,RF+Los group with additional losartan(10 mg?kg-1?d-1) gavage. Rats underwent sham operation(sham group) with normal saline gavage as control. Hear t changes of experimental rats were observed 12 weeks after operation. Results T he RF group developed hypertension of arterial systolic blood pressure(SBP) and myocardiac myocytes hypertrophy. The levels of collagen type Ⅰ,type Ⅲ,and fi bronectin in endocardium and surrounding intracardial coronary arteries adventit ia of the RF group were significantly increased as compared to those of the sham group. The SBP and the levels of collagen type Ⅰ,Ⅲand fibronectin were marked ly decreased in the RF+Los group as compared to those of the RF group.Expressio n of angiotensin Ⅱsubtype 1 receptor (AT1R) mRNA in the myocardium of the RF+L os group was significantly down regulated as compared to that of RF group. Concl usions Losartan can prevent the cardiac ventricular remodeling with left ventric ular hypertrophy (LVH) and myocardial interstitial fibrosis by the depression of renin-angiotensin system through the down-regulation of myocardiac AT1R mRNA.

Objective To investigate the effect of rosiglitazone on the expr es sion of PPAR?,TGF-a1 and PCNA and its mechanism on renal interstitial fibrosi s following unilateral ureteral obstruction(UUO) in rat kidney. Methods Thirty r ats were randomly assigned to shame operation group(sham group),UUO group, rosig litazone(5 mg穔g-1?d-1) treatment group after UUO. Immunohistochemistry,RT-PCR,Western blotting were performed to investigate renal pathological changes an d examine the expression of PPAR?,TGF-a1,PCNA on the 7th and 14th day in the kidney. Results In comparison with the shame group,the expression of PPAR?,TGF-a1,PCNA of UUO and treatment groups increased significantly(P

Objective To investigate renal histopathological changes and cli ni cal characteristics in 20 women with preeclamptic nephropathy or gestational pro teinuria.Methods Between 1999 and 2002, 20 women who suffered from preeclampsia or proteinuria during pregnancy underwent postpartum renal biopsies from fifth d ay to third month after delivery. One woman repeated her renal biopsy half year later. Each biopsy specimen was divided into three parts,and processed and stain ed for conventional light microscopy(LM), immunohistology (IH) and electron micr oscopy (EM) examination. The clinicopathological data were studied and women wer e followed up after discharge for a long time. Results Sixteen of 20 women were diagnosed as preeclampsia, whose altered glomeruli demonstrated a typical endoth elial lesion (endotheliosis), and mild to moderate proliferation of mesangial ce lls. IH revealed either negative or mild IgG、IgM and C3 deposits. Focal glomeru losclerosis (FGS) was observed in one of 16 cases, whose microproteinuria (0 49 g/24 h) lasted for more than one year, meanwhile the proteinuria of other 15 wo men disappeared completely within 3～6 months after delivery. Besides, one was I gA nephropathy (IgAN) complicated preeclamptic nephropathy, whose proteinuria de creased obviously after delivery, but remained microhematuria, and endothelial l esion disappeared in repeat biopsy after half year. One was IgAN and received a treatment of adrenocorticosteroid and immunosupressive agents because of macropr oteinuria. One was mild mesangial proliferative glomerulonephritis presenting co nstant microhematuria and microproteinuria. One was typeⅠmembranous nephropathy , whose proteinuria decreased remarkably after delivery as well. Conclusions Ren al histopathological changes of preeclampsis are typical endothelial lesion, and often recover completely within 6 months after delivery. Recovery may be delaye d in the case of FGS accompanied. Pregnancy may aggravate primary renal damage w hich will be improved after delivery. Postpartum renal biopsy is safe and benefi cial to early diagnosis, treatment and prognosis.

Objective To evaluate the effects of Ang Ⅱ on the expression of IQ domain GTPase-activating protein1 (IQGAP1) and apoptosis of glomerular cells,and to explore the role of IQGAP1 in Ang Ⅱ-induced apoptosis of glomerular cells.Methods Thirty-six male Wistar rats were randomly assigned to receive either saline or Ang Ⅱ by osmotic mini-pump,or be used as normal control.The systolic blood pressure and proteinuria were measured at day 7,14,21,28.After the animals were sacrificed at day 14,28 respectively,the kidneys were collected.Renal pathological change,glomerular cell apoptosis were observed.The expression of glomerular IQGAP1 was assessed by immunohistochemistry,immunofluorescence and Western blotting.The activation of caspase-3 and phosphorylation of extracellular regulated protein kinases 1 and 2 (ERK1/2) were determined by Western blotting.Results Ang Ⅱ-infused rats developed significant hypertension and marked proteinuria.Mild glomerular mesangial cell proliferation and mesangial matrix increase were also observed in Ang Ⅱ-infused rats.The number of apoptotic glomerular cells in Ang Ⅱ-infused rats was significantly more than that in normal control (P ＜ 0.05).The expression of IQGAP1 in glomeruli distributed linearly along the capillary loops.Ang Ⅱ infusion up-regulated the expression of glomerular IQGAP1,which had an significantly positive correlation with activation of caspase-3(r =0.689,P ＜ 0.05) and phosphorylation of ERK1/2 (r =0.658,P ＜ 0.05).Conclusion The enhanced expression of IQGAP1 may be involved in Ang Ⅱ-induced glomerular cells apoptosis via activation of ERK1/2 signaling pathway.

Objective To investigate the correlation of M-type phospholipase A2 receptor (PLA2R) genetic polymorphism in two single nucleotide polymorphisms (SNPs) with idiopathic membranous nephropathy (IMN) of Chinese Han population in Northeast China.Methods A total of 327 individuals were enrolled in the study including 95 adult patients with biopsy-proved IMN (IMN group) followed up for (25.4±11.6) months and 232 healthy people identified by healthy examination in China-Japan Union Hospital of Jilin University (HC group).Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genotype and allele frequency of rs35771982 and rs3828323 site in PLA2R gene.The x2 test was performed to compare the distribution difference of allelic frequency and genotype frequency of the two sites in PLA2R gene between two groups.Unconditional Logistic regression analysis was used to determine the risk factor of IMN.Results IMN and HC group were matched in male predominance and body mass index (BMI).Patients with IMN were older than the healthy controls and had higher Scr,serum total cholesterol (TC),24-hour urine protein level and lower serum albumin (Alb) level,lower estimated glomerular filtration rate (eGFR) than the healthy controls (all P ＜ 0.01).The CC genotype frequency and the C allele frequency at SNP rs35771982 site of PLA2R gene in IMN group were significantly higher than those in HC group (x2=13.658,P=0.001;x2=15.315,P=9.10× 10-5),whereas there was no distribution difference of genotype and allele frequency at rs3828323 site between two groups (x2=2.844,P =0.241; x2 =2.959,P=0.085).The CC genotype at rs35771982 site in patients with IMN was not related to,age,gender,BMI,blood pressure and several laboratory indexes such as Alb,TC,Scr,eGFR and 24-hour urine protein level (all P ＞ 0.05).Unconditional Logistic regression analysis revealed that the genotype at rs35771982,age,TC,Scr and eGFR were correlated with IMN occurrence.The CC genotype at rs35771982 was the risk factor of IMN (OR =4.408,95％CI 1.488-13.058).Conclusions The CC genotype and C allele at rs35771982 site in PLA2R may be associated with the susceptibility to IMN,whereas the correlation between gene polymorphism at rs3828323 site and IMN is not demonstrated.The CC genotype at rs35771982 is the independent risk factor of IMN in Chinese Han population in Northeast China.

Objective To evaluate the values of urinary liver-fatty acid binding protein (uL-FABP) and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in diagnosis of acute kidney injury (AKI) caused by obstructive nephropathy and in the prediction of renal prognosis.Methods Clinical data of 30 patients with obstructive nephropathy were collected prospectively.uL-FABP and uNGAL were measured by ELISA at various time points.Risk factors of the renal outcome were evaluated.The patients were followed up for at least one year.Results Patients with AK1 had higher levels of uL-FABP and uNGAL compared to those without AKI [700.00(154.62-1216.14) μg/g· Cr vs 26.90 (16.77-41.38) μg/g·Cr; 1266.69 (671.57-3396.07) μg/g·Cr vs 179.12 (90.98-215.16) μg/g·Cr,all P ＜ 0.01].Positive correlations of uL-FABP and uNGAL with serum creatinine were found (r =0.552,0.553,all P ＜ 0.01).The AUCs of uL-FABP and uNGAL to detect AKI were 0.925 and 0.900.Patients with non complete renal recovery had higher levels of uL-FABP before operation and 72-hour after operation compared to those with complete renal recovery (all P ＜ 0.01).Before operation,the AUC of uL-FABP to detect renal prognosis was 0.948,sensitivity was 85.7％ and specificity was 90.9％.72-hour after operation,the AUC of uL-FABP to detect renal prognosis was 0.935,sensitivity was 85.7％ and specificity was 90.9％.Kaplan-Meier analysis revealed that uL-FABP before operation over 366.57 μg/g · Cr or uL-FABP 72-hour after operation over 223.60 μg/g · Cr were closely related to the poor progression of renal function.Conclusions uL-FABP and uL-NGAL have good accuracy in detecting AKI.The level of uL-FABP before operation and 72-hour after operation is helpful to predict the renal outcome of obstructive nephropathy.

Objective To investingate the effect of low-density lipoprotein (LDL) on epithelial -mesenchymal transition and extracellular matrix (ECM) accumulation in human peritoneal mesothelial cells (HPMCs).Methods (1)HPMCs were randomly divided into control group,LDL group (100 mg/L) and LDL (100 mg/L) + lactoferrin (100 mg/L,LDL receptor blocking agent) group.After co-cultured for 24 h,the expression of LDL receptor in HPMCs was examined by immunofluorescence staining,and the LDL uptake by HPMCs was observed with oil red O staining.(2)HPMCs were cultured with different concentrations of LDL (0,25,50,100 mg/L).After co-cultured for 24 h,the change of cell morphology was observed by inverted phase contrast microscope,and the expression of α-smooth muscle actin (α-SMA) was examined by immunofluorescence.(3) HPMCs were randomly divided into control group (5.6 mmol/L glucose),mannitol group (M,2.18％ mannitol),low glucose group (LG,30 mmol/L),high glucose group (HG,120 mmol/L) and HG + LDL group (120 mmol/L glucose + 100 mg/L LDL).Cocultured for 48 h,the mRNA expression of α-SMA,E-cadherin and type 1 plasminogen activator inhibitor (PAI-1) was detected by real-time quantitative PCR,the protein expression of α-SMA was detected by Western blotting,the content of type I collagen (Col I) and PAI-1 in supernatant was detected by ELISA.Results (1) After co-cultured with LDL for 24 h,the expressin of LDL receptor was found on the cell membrane of HPMCs.Oil red staining showed that LDL could be uptaken into the cells and abolished by LDL receptor blocker.(2) HPMCs tended to be loosely intercellular connected to each ofher,and prsesnted significant formation of fibroblast-like spindle morphology.The cytoplasm immunofluorescence intensity of α-SMA gradually increased with the increase of LDL concentration.Compared to the control group,the expressions of α-SMA mRNA and protein were significantly increased,and the expression of E-cadherin mRNA was decreased in HG + LDL group(all P ＜ 0.05).But the expressions of the parameters above-mentioned were not significant different between HG group and HG + LDL group or between HG group and control group.(3) Compared with HG group or control group,the concentrations of Col Ⅰ [(19.27±0.17) μg/L vs (14.09±0.30) μg/L or (14.81±0.91) μg/L,all P ＜ 0.05] and PAI-1 [(498.24±76.91) ng/L vs (342.19±30.43) ng/L or (220.39±33.82) ng/L,all P ＜ 0.05] in supernatant of HPMCs were significantly up-regulated in HG + LDL group,meanwhile the expression of PAI-1 mRNA was significantly higer than that in control group (P =0.022).Conclusions HPMCs uptake LDL into cells via LDL receptors.LDL can induce HPMCs transdifferentiation in the condition of high glucose,increase the secretion of Col Ⅰ,inhibit the degradation of ECM through up-regulating the expression of PAI-1,and lead to ECM accumulation.

Objective To investigate the effect of hepatitis B virus X (HBX) gene on apoptosis and immune molecules of human proximal renal tubular epithelial cell line (HK-2).Methods The eukaryotic vector pcDNA3.1-myc-HBX containing HBX gene was transiently transfected into HK-2 cells by lipofectamine mediation.Untransfected HK-2 cells and those transfected with empty vector were used as controls.The TLR4 expression was detected by real-time PCR and Western blotting.The apoptosis of cells and expression of MHC-Ⅱ and CD40 were detected by flow cytometry,and the contents of IL-4 and IFN-γ in the supernatant were detected by EIISA.Results Compared with control groups,the number of apoptotic cells was significantly increased in the HBX transfection group (P ＜ 0.05),and the expressions of TLR4,MHC-Ⅱ and CD40 were also significantly increased in the HBX transfection group (all P＜0.05).IFN-γ level in the supernatant of HBX transfection group was higher (P ＜ 0.05),but IL-4 level was lower as compared to control groups (all P ＜ 0.05).Conclusions Over-expression of HBX gene may induce apoptosis of HK-2 cells and upregulate the expression of immune molecules of renal tubular epithelial cells leading to injury of cells and dysfunction of immunomicroenviroment.

Objective To identify the prevalence of different amyloid types in renal biopsies.Methods The renal biopsies of 205 patients diagnosed as renal amyloidosis from January 1990 to December 2011 were reassessed.Immunohistochemistry was performed with a penal of antibodies directed against λ-light chain,κ-light chain,amyloid A,fibrinogen,transthyretin,apolipoprotein A1,and lysozyme.Immune electron microscopy and gene analysis were performed when the results of immunohistochemistry were indeterminate.Results Among 205 patients,190 cases (92.7％) were classified as immunoglobulin light chain amyloidosis (AL),1 (0.5％) case as amyloid A amyloidosis and 1 (0.5％) case as fibrinogen A α-chain amyloidosis.The amyloid types of remaining 13 (6.3％) cases were undetermined.In the AL patients,the distribution of λ and κ was 6.6∶1.Conclusion AL is the most common form of renal amyloidosis in China,with a predominant light chain type of λ.