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Glucocorticoids have remained important anti-inflammatory agents in the treatment of chronic kidney disease (CKD).However,the use of glucocorticoids can invoke or enhance insulin resistance,which is closely associated with renal injury and serves as an independent risk of the occurrence and progression of CKD.On the other hand,CKD patients may have insulin resistance,which hampers the use of glucocorticoids in these patients.
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Objective To retrospectively evaluate the relevant factors for hepatitis B virus-associated glomerulonephritis (HBV-GN).Methods A total of 86 patients with pathologyproven HBV-GN and 135 HBV carriers with non-HBV-GN were included in this retrospective casecontrol study.Logistic regression analysis was used to detect the relevant factors for HBV-GN.Results On univariate analysis,the factors associated with HBV-GN were as follows: male (OR 2.79,95%CI 1.48-5.25,P=0.001),HBeAg positivity (OR 2.60,95%CI 1.49-4.53,P=0.001),HBV replication (OR 3.63,95%CI 1.80-7.33,P＜0.01),liver cirrhosis (OR 4.58,95%CI 1.41-14.91,P=0.011),and elevated alanine aminotransferase (ALT) (OR 2.53,95%CI 1.42-4.51,P=0.002).On multivariate analysis,the associations remained significant for male (OR 2.21,95%CI 1.12-4.33,P=0.022),HBV replication (OR 2.77,95%CI 1.28-5.97,P=0.01),liver cirrhosis (0R 4.55,95%CI 1.29-16.10,P=0.019) and elevated ALT (OR 1.96,95%CI 1.04-3.69,P=0.037).Compared with HBV-associated IgA nephritis (HBV-IgAN) in multivariate model,HBV-associated membranous nephropathy (HBV-MN) or membranoproliferative glomerulonephritis (HBV-MPGN) was significantly associated with male (OR 6.51,95%CI 1.76-24.11,P=0.005) and HBV replication (OR 7.22,95%CI 1.68-30.97,P=0.008).Conclusions Male,HBV replication,liver cirrhosis and elevated ALT may be predictive factors for HBV-GN.Compared with HBV-IgAN,HBV-MN or HBV-MPGN is significantly associated with male and HBV replication.
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objective To analyze the clinicopathological features and prognosis of antiglomerular basement membrane(GBM)disease,and evaluate the efficacy and safety of double filtration plasmapheresis(DFPP). Methods A total of 35 hospitalized patients diagnosed as anti-GBM disease in our department were enrolled in the study.All the patients were divided into 3 groups according to the manifestations at admission.Group Ⅰ∶24 patients with severe pulmonary hemorrhage or rapidly progressive glomerulonephritis(RPGN)received pulse methylprednisolone with or without DFPP,and then followed by prednisone and CTX.Group Ⅱ∶5 patients without severe pulmonary hemorrhage and RPGN received prednisone and CTX.Group Ⅲ∶5 ESRD patients and 1 normal renal function patient did not receive immunosuppression therapy.Anti-GBM antibody titer of pre-and post-DFPP in 4 patients was measured consecutively,and removal rate was calculated.Results The mean age of all the patients was(41.1±16.6)years.Sixteen patients(45.7%)presented Goodpasture's syndrome.Eighteen patients(51.4%)had anti-GBM glomerulonephritis alone,whereas one suffered solely from pulmonary hemorrhage.20%patients had positive P-ANCA serology.54.2%crescentic glomerulonephritis and 7 with other glomerulonephritis were revealed by kidney biopsy in 24 patients.Patients in Group Ⅰ showed more severe manifestation at admission:higher Scr level,higher titer of anit-GBM antibody,greater percentage of crescents.Within the follow-up period,7 patients died and kidneys of 50%patients survived.No patient died in Group Ⅱ and Ⅲ.The elder age,anemia,higher Scr(＞300 μmol/L),oliguria or anuria,emergency hemodialysis at admission,and more glomerular sclerosis were predictors of poor prognosis.The anti-GBM antibody was negative after 4 to 6 sessions of DFPP.and the mean removal rate was 55%.During total 94 DFPP sessions,there was no unacceptable morbidity. Conclusions Different therapy strategy is necessary for anti-GBM disease with different clinical manifestations.DFPP is an effective and safe clearance way of anti-GBM antibody.
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Objective To analysis if intedeukin-1β (IL-1β) can regulate human mesangial cells (HMC) to uptake oxidized low density lipoprotein (Ox-LDL) and if the effect of IL-lβ be changed through the lectin-like oxidized low-density lipoprotein receptor 1 (LOX-l)pathway. Methods The uptake of HMC to Ox-LDL stimulated by IL-1β was observed using Oil Red "O" and flow cytometry. The level of LOX-1 in HMC induced by IL-1β and Ox-LDL was examined using real-time PCR and Western blotting. Results Uptake of Ox-LDL and Dil-Ox-LDL by HMC was up-regulated upon stimulation with IL-1β in a dose- and time-dependent manner. Intracellular mean fluorescence density of Dil-Ox-LDL with LOX-1 blocker in IL-1β stimulation group was decreased compared to that without blocker. The peak level of LOX-1 mRNA reached after 6 h of stimulation and was as high as 6.87-fold of control. IL-1β could induce LOX-1 mRNA expression in a dose-dependent manner. Treated with 10 μg/L IL-1β for 12 h, the upregulation effect on LOX-1 mRNA was as high as 6.57-fold of control. IL-1β could induce LOX-1 protein expression in a time- and dose-dependent manner. The peak level of LOX-1 protein reached after 24 h of stimulation of 5 μg/L IL-1β and was as high as 1.88-fold of control. Treated with 10 μg/L IL-1β for 24 h, the up-regulation effect on LOX-1 protein reached peak and was as high as 2.57-fold of control. IL-1β could induce LOX-1 mRNA and protein expression in a dosedependent manner. Conclusion The expression of LOX-1 can be up-regulated by IL-1β in a dose-dependent manner and the enhanced uptake of HMC to Ox-LDL stimulated by IL-1β partly through the LOX-1 pathway, which means the dyslipidemia of HMC can be enhanced by inflammatory cytokines.
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Objective To study the effects of acyl-coenzyme A cholesterol acyltransferase inhibitor(ACATI, 58-035) on cholesterol homeostasis in lipid-loaded human mesangial cell line (HMCL) . Methods Oil red O was used to examine the lipid droplet . MTT was performed to detect the cell proliferation . High performance liquid chromatography (HPLC) was used to measure intracellular free cholesterol (FC) and cholesterol ester (CE) . Western blot was used to demonstrate the protein level . Real-time PCR was performed to detect the mRNA expression .Results In HMCL loaded with 100 mg/L of low density lipoprotein (LDL), 10 mg/L 58-035 significantly inhibitted the formation of lipid droplets and CE mass (ratios over control, 1 .91±0 .36 and 1 .07±0 .30 respectively, P＜0 .01) without toxic effect . It further enhanced the ACAT1 protein expression (ratios over control, 1 .27 and 1 .77 respectively) without significant influence on mRNA level, since the activity of ACAT1 pl promoter by transient transfection was not affected by either LDL or ACATI . 100 mg/L LDL down-regulated the mRNA of LDL receptor (LDLR) (ratio over control, 0 .08±0 .02, P＜0 .01)and up-regulated that of ATP binding cassette transporter 1(ABCA1)(ratio over control, 2 .97±0 .39, P＜0 .01) . The mRNA expression of ABCA1 was further upregulated (ratio over control 4 .41±1 .27, compared with LDL group P＜0 .05), and LDLR was further down-regulated (ratio over control 0 .04±0 .005, compared with LDL group P＜0 .01) in the presence of 10 mg/L ACATI 58-035 . Conclusions The CE mass in lipid-loaded HMCL can be decreased in the presence of ACATI, accompanied by further down-regulation of LDLR mRNA expression and up-regulation of ABCA1 protein and mRNA expression . It is physiological feedback to inhibit free cholesterol accumulation to maintain cholesterol homeostasis .
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Objective To observe the impact of IL-1β on the expression of lectin-like oxidized LDL receptor 1 (LOX-1) and ATP-binding cassette transporter A1 (ABCA1) in human mesangial cell line (HMCL), and its association with cholesterol homeostasis of HMCL. Methods Levels of LOX-1 and ABCA1 of HMCL induced by IL-1β were examined by using real-time PCR and Western blot. Results IL-1β up-regulated LOX-1 mRNA and protein expression. Treated with 5 μg/L IL-1β, the levels of LOX-1 mRNA and protein reached the peak after 6 h and 24 h of stimulation and were 6.87 folds and 1.88 folds of control rspectively. The expression of ABCA1 mRNA and protein of lipid-loaded HMCL was down-regulated by IL-1β Stimulated with 5 μg/L IL-1β the expression of ABCA1 mRNA and protein decreased to the lowest level, 19.0% and 50.62% of the baseline respectively. Conclusions The expression of LOX-1 can be up-regulated while the expression of ABCA1 can be decreased by the stimulation of IL-1β. IL-1β can enhance dyslipidemia and influence the balance of cholesterol homeostasis of HMCL.
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ObjectiveTo clarify why accelarated atheroslcerosis is complicated in chronic kidney disease patients, and to investigate whether endoplasmic reticuhm (ER) stress can be observed in acetylated low density lipepmtein (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 apeptosis. Oil red O was used to examine the lipid droplet. High performance liquid chromatography was used to measure intracelhlar free cholesterol (FC) and cholesterol ester (CE). Western blot was applied to demonstrate the protein level of acylcoenzyme 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. ConclusionIn THP-1 macrophages foam cell, apoptosis can be induced by ACLDL accompanied by ER stress pathway activation.