Objective To investigate the cause, prognosis and risk factors of hospitalized patients with acute renal failure(ARF). Methods The clinical data of patients with ARF in our hospital from December 2003 to December 2006 were studied retrospectively. Results There were 108 744 admissions during the study period and 320 met with the diagnostic criteria of ARF. Of 320 ARF patients, 135(42.2%) were indentified with the onset of the disease over or at the age of 60. Infection, heart failure and drug were the major causes of ARF. The overall mortality rate of ARF patients was 31.9%. The mortality rate of the elderly was significantly higher than that of the non-elderly. The Logistic regression analysis revealed that heart failure, respiratory failure and malignant tumor were the related risk factors of prognosis. The mortality in replacement therapy group was lower than that in conservative treatment group(23.2% vs 35.6%, P<0.05). Conclusions The incidence and mortality of hospitalized patients with acute renal failure are high. The prognosis of replacement therapy group is better than conservative treatment group.

Objective To evaluate the prophylactic efficacy of compound sulfamethoxazole （SMZco） combined with ganciclovir on severe pulmonary infection in the early stage of renal transplantation. Methods Between January 2005 and January 2006, two hundred and forty renal allograft patients in our hospital were enrolled in this study. All the patients were divided into two groups. Group A（n=84）received oral SMZco combined with intravenous ganciclovir. Group B（n=156）received intravenous ganciclovir only as control. According to the time of SMZco administration, group A was divided into two subgroups: group A1( within 2 weeks after transplantation, n=43) and group A2 (more than 2 weeks after transplantation, n=41). All the patients were followed up for 9 months. Incidence of pulmonary infection and effects on graft function by SMZco at different time point were investigated. Results The incidence of severe pulmonary infection and mortality of infection were significantly lower in group A than those in group B （2/84 vs 16/156, P=0.027; 0/2 vs 2/16, P<0.01）. There were no significant differences between two groups in terms of age, gender, warm or cold ischemia, complement dependent cytotoxicity test results, incidence of urinary infection and Scr. The incidence of elevated Scr was significantly lower in group A2 than that in group A1（15/43 vs 2/41, P<0.01）, however, all the elevated Scr returned to basal level within 1 week after SMZco was discontinued. Conclusions Oral SMZco combined with ganciclovir administration after renal transplantation is effective on preventing severe pulmonary infection and thus improves graft and recipient survival. The administration of oral SMZco initiated more than 2 weeks after transplantation is better for graft function.

Objective To investigate the effects of tg19320, a small peptide, interfering with IgG-FcγR interaction on the adhesion of neutrophils to endothelium and the expression of intercellular adhesion molecule 1 (ICAM-1)in endothelial cells and its possible mechanism. Methods Tg19320 was prepared by solid-phase peptide synthesis. ANCA IgG was isolated from the serum of active ANCA-associated systemic vasculitis (AASV) patients. When primary human umbilical vein endothelial cells (HUVEC) grew into confluence in cytokine-free conditions, the cells were stimulated with TNF-α, human normal IgG, ANCA IgG and ANCA IgG+tg19320 respectively. HUVEC were pretreated with tg19320 for 45 minutes before being stimulated by ANCA IgG. Non-activated neutrophils was added to treat HUVEC and adhesion was measured by cell count. The expression of ICAM-1 mRNA and protein was assessed by real-time PCR and Western blot respectively. Soluble ICAM-1 (sICAM-1) was determined using ELISA technique. Phosphorylation of IκB-α was assessed by Western blot. Results ANCA IgG significantly up-regulated the expression of ICAM-1 in HUVEC and promoted sICAM-1 release(P<0.05)， and TNF-α enhanced the effect of ANCA. These effects were almost completely abolished by tg19320 both at protein and mRNA level. Furthermore, ANCA IgG increased the IκB-α phosporylation in HUVEC and tg19320 could inhibit the effect. Conclusions ANCA IgG can modulate the expression of ICAM-1 and sICAM-1 release in endothelial cells. FcγR probably play a critical role in the ICAM-1 expression up-regulated by ANCA, which is mediated in part through NF-κB signaling pathway. Tg19320 has protective effect on endothelium in AASV in vitro.

Objective To study the role of JAK-STAT singal transduction pathway in the interstitial fibrosis of unilateral ureter obstruction (UUO) mice. Methods Mice UUO model was established and the phosphorylation of JAK-STAT was examined at day 1, 4, 7 and 14 after ligation of the ureter. Mice in the treatment group were treated with daily injection of selective JAK2 inhibitor AG490 starting 2 h before ureter ligation until sacrifice while vehicle alone was given to mice in the model control group. Mice were sacrificed at day 14 after the establishment of model. Renal tubular lesion and interstitial fibrosis were assessed on paraffin section. Immunohistochemistry was used to detect renal macrophage infiltration and α-SMA expression. The expression of collagen Ⅲ and MCP-1 mRNA was measured by RT-PCR. Phosphorylation of JAK2 and STAT1 was examined by Western blotting. Results JAK2-STAT1 signaling transduction pathway was activated in UUO model. The activation of JAK2-STAT1 was closely correlated with the progression of renal injury, tubular histological lesions and interstitial fibrosis. AG490 treatment significantly inhibited the phosphorylation of JAK2 and STAT1 (P<0.01). AG490 treatment also significantly reduced tubular lesions[(21.7±1.7)% vs（49.4±1.0）%] and interstitial fibrosis (1.0±0.1 vs 2.3±0.2), α-SMA expression (0.9±0.1 vs 2.1±0.2) and macrophage accumulation[(13.3±1.6) cells/HPF vs (34.4±1.0) cells/HPF](all P<0.01). In addition, AG490 significantly inhibited the expression of collagen Ⅲ and MCP-1 mRNA. Conclusion JAK-STAT signaling plays an important role in renal tubulointerstitial inflammation and fibrosis.

Objective To investigate the effect of high glucose on renal tubular epithelial-mesenchymal transition， and to analyze the relationship between high glucose and transforming growth factor β1(TGF-β1) and the mechanism of renal interstitial fibrosis. Methods HKC and Smad7-overexpression HKC cells were grown in DMEM/F12 medium containing 5%~10% newborn calf serum. They were cultured for 16 h in free serum medium after 80% cells were adhered onto the surface of the flask. Afterwards, they were stimulated by high glucose (glucose concentration: 25 mmol/L and 50 mmol/L). The expression of α-SMA, E-cadherin and fibronectin was detected by Western blot while the supernatant level of TGF-β1 was detected by ELISA. Cell motility and migration was evaluated using Boyden chamber motogenicity assay. Results In HKC induced by high glucose, the expression of α-SMA and fibronectin protein was highly up-regulated while the expression of E-cadherin protein was down-regulated. The expression of TGF-β1 was up-regulated in a dose-dependent manner. These above-mentioned effects could be obviously inhibited by anti-TGF-β1 antibody. The protein expression of α-SMA, fibronectin and E-cadherin had no obvious change in Smad7-overexpression HKC induced by high glucose. HKC exhibited enhanced motility and invasive capacity in high glucose groups, compared to that in control group. Migrated cell counting was (12.4±3.7) and (18.6±4.4) cell/HP in 25 and 50 mmol/L glucose groups respectively. Conclusion High glucose may induce renal tubular epithelial-mesenchymal transition through TGF-β1 pathway, which can be inhibited by blocking the Smad signal pathway.

Objective To investigate the activation of NF-κB and regulation by ubiquitin(Ub)-proteasome pathway in the aorta of rats with chronic renal failure（CRF）. Methods The CRF rat model was established by right nephrectomy and left branch renal artery ligation. The CRF rats were were randomly divided into simple CRF group (n=20) and CRF+M group (n=20, treated by peritoneal injection, with MG-132, 10 μg&#8226;kg-1&#8226;d-1). Ten normal rats were used as control group ( CON ). The NF-κB and the Ub mRNA expression were detected by RT-PCR, and its protein expression was analyzed by immunohistochemistry method. The activity of NF-κB was mesured by EMSA method. The concentration of IL-1 and TNF-α was detected by ELISA. Results Compared with the CON group, the concentration of serum IL-1 and TNF-α was increased significantly in CRF group [IL-1: (9.02±1.29) vs (2.74±0.96) mg/L, P<0.01; TNF-α: (50.02±9.52) vs (14.04±1.29) mg/L, P<0.01] at month 4 after operation. The mRNA expression of NF-κB and Ub in the aorta of CRF group was 1.38 and 1.29 times as that of CON group（P<0.01）, and the protein expression of NF-κB and Ub was 3.75 and 20.5 times as that of CON group（P<0.01）. Compared with the CON group, the activity of NF-κB in the aorta of rats of CRF group was elevated markedly at month 4 after operation（P<0.01）. All the indices were further increased at month 6 after operation. Compared with CRF group, the concentrations of serum IL-1 and TNF-α were decreased significantly in CRF+M group [IL-1: (2.94±0.33) mg/L, P<0.01; TNF-α:(12.80±2.12) mg/L, P<0.01]. The mRNA and protein expression of NF-κB and Ub were also decreased markedly(P<0.01), and the activity of NF-κB was decreased significantly at month 4 to 6 after operation(P<0.01). But the amount of ubiquitnative protein was increased significantly in the aorta of CRF+M group as compared to CRF group (P<0.01). Conclusion The inflammatory signal pathway of ubquitin-proteasome-NF-κB pathway was activated in the aorta of CRF rats, and the proteasome was probablely an important pharmacological intervention target to regulate the activation of NF-κB.

Objective To observe the effects of calcium dobesilate on the expression of CD34 and von Willebrand factor（vWF） in peritubular capillary (PTC) in renal tissues of rats with chronic arisolochic acid nephropathy （CAAN） and to explore the probable mechanism concerned. Methods Sixteen Wistar rats were infused with Caulis aristolochia manshuriensis decoction for 12 weeks, then randomly divided into 2 groups. NX group rats(n=8) were infused with distilled water and treatment group(n=8) with calcium dobesilate at the following 4 weeks solely. Control group rats(n=8) were infused with distilled water for the 16 weeks. At week 16, all the rats were sacrificed. Specimens of blood and urine were collected to detect the blood urea nitrogen(BUN), serum creatinie (Scr) and urine protein. HE and Masson staining was used to observe the pathology of the kidney. Immunohistochemistry was used to detect the expression of CD34 and vWF. Results Urinary protein, Scr and BUN in calcium dobesilate treatment group were much lower than those in NX group (P<0.05). The A value of CD34＋ increased significantly in calcium dobesilate treatment group [(16.72±4.17)×103] compared with NX group [(3.19±1.40)×103] at week 16 (P<0.01). The A value of vWF＋ decreased in calcium dobesilate treatment group [(10.16±1.68)×103] compared with NX group[(18.66±4.65)×103] at week 16(P<0.01). Conclusion Calcium dobesilate can increase the expression of CD34 and the density of peritubular capillary (PTC) in renal tissues of CAAN rats, and reduce the expression of vWF and the formation of microthrombosis.

Objective To observe the expression of bone matrix proteins and the change of intima-tunica media thickness ratio in diabetic rat small renal artery and to explore their correlation and effects on diabetic nephropathy. Methods Seventy healthy SD rats were randomly divided into diabetic group(DN, n=40) and normal control group(N, n=30). DN rat model was induced by streptozotocin (STZ) intraperitoneal injection and the N group rats were given the same dose of citrate buffer. Thirty-five rats were successfully induced in DN group. The rats were sacrificed at week 4,12 and 24, respectively. The protein and mRNA expression of core-bind factor alpha 1（Cbfα1）, bone morphogenetic protein 2（BMP-2）and matrix Gla protein（MGP）in small renal artery were detected by immunohistochemistry, in-situ hybridization and real-time PCR at each time point. Results Cbfα1 and BMP-2 were expressed obviously in small renal artery of DN group by immunohistochemistry stain and in-situ hybridization from 4 to 24 weeks compared with N group at each time point, reaching the peak at week 24. Real-time PCR showed that the MGP mRNA was evidently increased at week 4, slightly decreased at week 12, lowest at week 24 in DN group. The BMP-2 mRNA began to increase from week 4 onward, being peak at week 24 in DN group. The ratio of intima to tunica media thickness had no significant difference in DN group compared with N group at week 4, but at week 12 and 24 there were significant difference between them. There was a positive correlation between Cbfα1 and BMP-2 expression, but they were negatively correlated with the expression of MGP. The ratio of intima to tunica media thickness was significantly correlated with the expression of Cbfα1 and BMP-2. Conclusions The ratio of intima to tunica media thickness is positively correlated with Cbfα1 and BMP-2 in small renal artery of early DN. Cbfα1, BMP-2 and MGP may be involved in the progression of vascular lesions in DN.

Objective To establish a mini pig model suitable for interventional studies in vivo. Methods The endothelia of unilateral renal arteries in 8 purebred Chinese experimental mini pigs (CEMP) was denuded by inflated balloons after the animals were fed with high cholesterol diet for 13 weeks. The CEMP were fed with high cholesterol diet continuously till the 40th week. The levels of blood lipid panel and creatinine were tested at week 1, 14 and 40. Bilateral renal arteries were examined with intravascular ultrasonography at week 14 and 40. The vessel samples were collected at week 40 and stained with haematoxylin-eosin, Masson trichrome technique, oil O and anti-macrophage immunohistological technique. Results Significant differences of blood lipid panel and creatinine were found between week 1 and week 40. Focal ischemic renal injury could be observed pathologically. Renal arteries of CEMP were suitable for interventional procedure such as angiography and intravascular ultrasonography. Cross-sectional information of vessels could be provided clearly by intravascular ultrasonography and the intima-median thickness of injured renal arteries was much thicker than that of non-injured ones [(0.89±0.03) mm vs (0.30±0.02) mm, P＜0.05] as evidenced by this diagnostic technique. Pathological findings demonstrated the atherosclerotic profiles of the injured renal arteries. Fibrous and fibro-fatty plaques were the main pathologic types in this CEMP model. Conclusions An animal model with renal arterial atherosclerosis mimicking the progression of atherosclerotic renovascular disease, which is suitable for interventional procedure is established successfully. Intravascular ultasonography may have potential clinical prospect on the evaluation of atherosclerotic renovascular disease.