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Objective To investigate the efficacy and safety of Tripterygium wilfordii Hook F (TwHF) combined with renin-angiotensin system (RAS) blockers in chronic kidney disease (CKD) stages 2~3 of IgA nephropathy. Methods 109 patients were randomized into the observation group and the control group. On the basis of taking RAS blockers, patients in the observation group received TwHF, and patients in the control group received methylprednisolone. The proteinuria, renal function and adverse effect were observed during treatment. Results At 3, 6, 9 and 12 months of treatment, proteinuria in the two groups was lower than the baseline(P 0.05). Besides, there was no significant difference in terms of proteinuria, eGFR and effective rate in the two groups. The occurrence rate of adverse effects was 9.8% vs 27.4% and there was significant difference in the two groups (P < 0.05). Conclusions TwHF combined with RAS blockers can decrease proteinuria, protect renal function and have less adverse effects, and it is a useful therapeutic options for CKD stages 2 ~ 3 of IgAN.
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Objective To conduct a prospective,randomly controlled trial,evaluating the combination of tacrolimus,corticosteroids and entecavir for the treatment of adult patients with biopsyproven hepatitis B virus-associated membrane nephropathy (HBV-MN).Methods A total of 38 patients with biopsy-confirmed HBV-MN were randomized to the tacrolimus group (n=19) and the control group (n=19).Patients in tacrolimus group received combination therapy of tacrolimus (0.05 mg·kg-1 · d-1),corticosteroids (prednisone acetate,0.5 mg· kg-1 · d-1) and entecavir (0.5 mg/d),whereas patients in control group received entecavir mono-therapy (0.5 mg/d).The primary end point was the percentage of patients reaching complete remission (CR) or partial remission (PR).Results The probability of remission in the treatment group was 88.89％ and 94.44％ after 6 and 12 months,but only 38.89％ and 58.82％ in the control group,respectively.The decrease in proteinuria was significantly greater in the treatment group.Entecavir was used for the treatment of hepatitis in all patients,which caused the disappearance of serum hepatitis B viral DNA(HBV-DNA) and the normalization of ALT and AST levels in 3 months.Notably,two patients in the control group and one patient in the treatment group reached the secondary end point.One patient in the tacrolimus-treated group showed a relapse during the taper period.Conclusion This treatment protocol not only can control the replication of HBV-DNA but also can reduce proteinuria and preserve renal function,it is one of useful therapeutic options for patients with HBV-MN.
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ObjectiveTo investigate the effects and molecular mechanism of endoplasmic reticalam stress (ERS) on albumin-induced apoptosis in renal proximal tubular cells (HKCs). MethodsWestern blot was performed to detect the relationship of the expression of glucose-regulated protein 78 (GRF78) and CCAAT/enhancer-binding protein-homologous protein (CHOP) with the action time and concentration of haman serum albumin (HSA). Expression levels of CHPO mRNA and protein in HKCs after CHOP siRNA transfection were examined by real-time fluorescence quantitative PCR and Western blot respectively. Annexin-V-FITC and PI doable staining cytometry was used to detect the apoptosis of HKCs induced by HSA and influenced by CHOP siRNA. Results(1)After HKCs were stimulatde by 0, 5, 10, 20 g/L albumin for 24 hours respectively, the expression of GRP78, CHOP and HKCs apoptosis were increased with the albumin concentration (P<0.01). After HKCs were stimulated by 20 g/L albumin for 0, 6, 12, 24, 36 hours respectively, the expression of GRP78 was up-regulated at 6-hour, while CHOP and HKCs apoptosis were increased at 12-hour, and significant differences were found among groups (P<0.01). (2) CHOP siRNA significantly inhibited albumin-induced HKC CHOP mRNA and protein expression, as well as HKC apoptosis (P<0.01). ConclusionsRenal tubular cells exposed to high protein load result in EBS. ERS may subsequently lead to tubular damage by activation of pro-apoptosis factor CHOP.
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Objective To explore the influence of albumin-activated renal tubular epithelial cells (RTECs)on peritubular capillaries in co-culture system and its potential mechanism. Methods Endocytosis of TRITC labeled bovine scrum albumin (TRITC-BSA) by HKC was detected by laser scanning confocal fluorescence microscope. HKC or HKC transfected with cubilin (endocytic receptor of albumin) siRNA or pre-treated with rotenone was incubated with albumin(20 g/L) for 24 h respectively. Fluorescence probe technique and spectrometry were applied for determination of intracellular superoxide anion O2-and H2O2 in supematant. Then, the albumin-aetivated-HKC, pretreated-HKC with cubilin siRNA or rotenone, was cultured with HUVEC for 24 h in co-culture system respectively. HUVEC proliferation was determined by MTT and cellular apoptosis was analyzed by flow cytometry. Tabular morphogenesis of endothelial cells was examinedby microscopy. Results TRITC-BSA uptake was obviously lower in HKC transfected with cubilin siRNA. Intracellular generation of O2-and H2O2 in culture supernatant was increased in dose-and time-dependent manner after stimulating with albumin. The levels of O2-and H2O2 were suppressed by cubilin siRNA and rotenone. In co-culture system, albumin-activated-HKC induced endothelial cells apoptosis and inhibited their capillary tubular morphogenesis. Pretreatment of HKC with cubilin siRNA or rotenone could suppress endothelial cells apoptosis and promote capillary tubular morphogenesis. Conclusions There may be a crosstalk between RTECs and peritubular microvascular endothelial cells in renal proteinurie diseases. The generation of ROS by albumin-activated RTECs may play an important role in this process.
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OBJECTIVE: To investigate the curative effects and side effects of hirudin in treating immunoglobulin A nephropathy (IgAN) with hematuria and minimal proteinuria in a short-term. METHODS: Two hundred and sixty-two histologically confirmed cases of IgAN with hematuria and minimal proteinuria from 1998 to 2007 were randomly divided into hirudin-treated group (peroral administration of Maixuekang capsules) and dipyridamole-treated group (peroral administration of dipyridamole). In the two groups, contrast analysis of conformation and counts of erythrocytes in urine, urine protein quantitation in 24 hours, levels of serum creatinine (Scr) and creatinine clearance rate (Ccr), blood lipid, five items of blood clotting and side effects was performed. RESULTS: After six-month treatment, the anisotrophy rate and the counts of erythrocytes in urine, and the urine protein quantitation in 24 hours in hirudin-treated group were decreased distinctly as compared with pre-treatment (P<0.01) and dipyridamole-treated group (P<0.05). On the other hand, Ccr was increased obviously in hirudin-treated group as compared with pre-treatment and dipyridamole-treated group (P<0.01). The blood lipid was also ameliorated in hirudin-treated group, but there was no significant difference. The anticoagulation effect of hirudin was better than dipyridamole (P<0.01). Efficacy assessment showed that the total response rate, complete remission rate and predominance remission rate in hirudin-treated group were higher than those in dipyridamole-treated group. Few side effects were found in both groups, and the rate of adverse reaction in gastrointestinal tract was lower in hirudin-treated group as compared with that in dipyridamole-treated group (P<0.05). CONCLUSION: Compared with dipyridamole, hirudin has superiority in kidney protection and decreasing the anisotrophy rate, counts of erythrocytes in urine and the urine protein.
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Objective To analyze the clinical feature and its risk factors on 112 episodes of urinary tract infection (UTI) in patients with lupus nephritis. Methods 112 episodes of UTI in patients with lupus nephritis in our department during the past 5 years were reviewed retrospectively. Epidemiological data and information on urinary symptoms, disease activity (SLEDAI) , leukocyte and platelet data were collected. Autoantibodies, complement levels, urine culture, and antibiogram were determined. Urological studies were carried out. The use of corticosteroids and (or) immunodepressive were also investigated. Results The prevalence of UTI in lupus nephritis patients was 36.5% , and complexity infection(58%) was the main UTI . Symptomatic UTI was 62% , and symptomless UTI was 38% . The mean SLEDAI score was 15.7(SD3.05) , which influenced the onset of UTI (P1/100 IU/ml, leucopenia and thrombocytopenia (P
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AIM: To investigate the role of nuclear factor- κB (NF- κB) in the expression of monocyte chemoatractant protein- 1 (MCP- 1) in human mesangial cells (HMCs) induced by oxidized low- density lipoprotein (Ox- LDL).METHODS: HMCs were used as target cells. Inhibitory κBα (IκBα) and MCP- 1 protein level was measured by cell ELISA.Activities of transcriptional factors NF- κB were determined by electrophoresis mobility shift assay (EMSA). Immunohistochemistry was used to detect the translocation of Rel p65. RESULTS: NF - κB DNA - binding activation in MCs was observed when 10-100 mg/L Ox - LDL was added to the medium, and 50 mg/L Ox - LDL caused the strongest effect (8.50 ± 1.14, P ＜ 0.01vs control; P ＜ 0.05 vs 10, 25 and 100 mg/L Ox - LDL). The most optimal stimulation time was 60 min ( 11.0 ± 2.11, P ＜0.01 vs control; P ＜ 0.05 vs 30 min or 240 min). IκBα protein level in MC dropped down most obviously after 60 min incubation with 50 mg/L Ox - LDL (0.050 ± 0.006, n = 5, P ＜ 0.01 vs control), while MCP- 1 expression level was the highest (0.331± 0.016, n = 5, P ＜ 0.01 vs control). The translocation of Rel p65 from cytoplasm to nucleus was detected too. NF - κB inhibitor pyrroledithiocarbomate (PDTC) could inhibit these effects induced by Ox- DL. CONCLUSION: Activation of NF- κB regulate the expression of MCP- 1 in HMCs induced by Ox - LDL.
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Objective To investigate the protective role of glycyrrhizin on experimental obstructive nephropathy in rats. Methods The model of obstructive nephropathy was induced by unilateral uretera l ligation in rats and the animals were sacrificed at 12 h and 3,14,28,56 d resp ectively after operation. Specimens were taken from the cortex of kidney. In re nal stroma, routine morphological examinations and counts of karyocyte were made , the expression of collagen type Ⅰand type Ⅲ were also detected by immunohist ochemical staining,then, semi-quantified by EIG image analysis system. Results A progressive fibrosis was observed in renal stroma of the mod el. 12 h after operation, counts of karyocyte increased markedly i n renal stroma in groups of treatment and pretreatment with glycyrrhizin compar ed with that in sham-operation group（P<0.05）,and decreased distinctly compared with that in saline treated group（P<0.01）, but no significant di fference was found between treatment group and pretreatment group（P>0.05） ;3 d after operation, in group treated or pretreated with glycyrrhizin. The e xpression of collagen type Ⅰ increased markedly compared with that in sham-o peration group（P<0.01） in renal stroma, but decreased notably compare d with that in saline treated group（P<0.01）,while, there was not any diffe rence between treatment group and pretreatment group（P>0.05）. The expressi on of collagen type Ⅲ in renal stroma was almost the same as that of coll agen type Ⅰ. Conclusion Glycyrrhizin has some therapeutical bu t no preventive effect to experimental obstructive nephropathy in rats.
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AIM: To investigate the role of nuclear factor-?B (NF-?B) in the expression of monocyte chemoatractant protein-1 (MCP-1) in human mesangial cells (HMCs) induced by oxidized low-density lipoprotein (Ox-LDL). METHODS: HMCs were used as target cells. Inhibitory ?B? (I?B?) and MCP-1 protein level was measured by cell ELISA. Activities of transcriptional factors NF-?B were determined by electrophoresis mobility shift assay (EMSA). Immunohistochemistry was used to detect the translocation of Rel p65. RESULTS: NF-?B DNA-binding activation in MCs was observed when 10-100 mg/L Ox-LDL was added to the medium, and 50 mg/L Ox-LDL caused the strongest effect (8.50?1.14, P
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Objective To investigate the effects of glycyrrhizin-18? on the expressions of connective tissue growth factor (CTGF) and transforming growth factor-?1 (TGF-?1) in renal interstitium in rats with obstructive nephropathy. Methods A total of 100 Wistar rats were divided into experiment group (include prophylaxis group with glycyrrhizin-18?, glycyrrhizin-18? treatment group, and group with normal saline) and control group (sham operation group). Models of rats with obstructive nephropathy were established by unilateral ureteral ligation. The rats were sacrificed at 7, 14, 28, and 56 d after operation and specimens were taken from the renal cortex. The morphopathological changes in the renal interstitium were observed byr light and electron microscopy. CTGF, TGF-?1, and collagen type Ⅲ were detected by immunohistochemical staining. The measured data were evaluated by EIG image analysis system. Results In the renal interstitium, there was progressive fibrosis in the model. Semi-quantitative analysis indicated that the expression levels of CTGF, TGF-?1, and collagen type Ⅲ in the renal interstitium in glycyrrhizin-18? treatment and prophylaxis groups were markedly higher than those in the sham operation group (P0.05). The expression of CTGF in the renal interstitium was closely correlated with those of TGF-?1 and collagen type Ⅲ (P