Objective To investigate the effect of leflunomide and prednisone in treating refractory nephropathy syndrome.Methods The 60 refractory nephropathy patients in our hospital from Oct,2000 to May,2003 were divided into two groups at random.Paients in test group received leflunomide and prednisone.Patients in control group received mycophenolate mofetil and prednisone.Clinical data were observed in the 2nd,4th,6th,8th,12th,16th,20th,24th and 28th week.Results After receiving leflunomide therapy in the test group,the proteinuria was decreased significantly(P0.05),but rate of showing efficacy in 12th week in Leflunomide group was higher than mycophenolate mofetil group(P

Objective To investigate the efficacy and safety of mycophenolate mofetil combined with methylprednisolone and lamivudine on the treatment of hepatitis B virus associated glomerulonephritis(HBV-GN).Methods Twenty-four patients with hepatitis B virus associated glomerulonephritis were confirmed by renal biopsy and immunohistochemistry,these participant patients were admitted to the Third Affiliated Hospital of Sun Yat-Sen University from Jan,1999 to Jan,2004.They were treated by MMF combined with methylprednisolone and lamivudine.The initial dosage of MMF was 1.0~1.5 g/d.Methylprednisolone at the dosage of 0.4 mg/(kg?d)was used at the beginning of the combined treatment.Lamivudine was in the dosage of 0.1 g/d.The duration of the treatment was six months.Regular test was conducted every two weeks.Results Nine cases had fully remission,11 cases had partial remission and 4 cases had no efficiency;no patient deterioration.Renal and hepatic function remained stable,blood cell didn't decrease and the reproduction of HBV didn't increase during the treatment.Conclusion MMF combined with methylprednisolone and lamivudine is an effective and safe method for HBV-GN.

Objective To investigate the serum leptin levels of chronic hemodialysis patients and its relation to their nutritional status.Methods Twenty-nine maintenance hemodialysis patients were included in the study.TSF(triceps skin fold),BMI(body mass index) and FAT%(content of fat),lymphocyte count,serum albumin,globulin,total iron binding capacity,BUN,creatinine,cholesterol,triglyceride and leptin were measured.Malnutrition-inflammation score(MIS) was used to assess the patients nutritinal status.Results Levels of leptin were positively correlated with BMI,FAT%,TSF and MIS(P

Objective To explore the relationship between reversed dipper blood pressure (BP) pattern with target organ damage in Chinese chronic kidney disease (CKD) patients. Methods A total of 1 116 CKD patients from the Third hospital of Sun Yat?sen university were enrolled from May 2010 to April 2014, all of whom carried ambulatory blood pressure monitoring (ABPM), and clinical data and ultrasonography were collected. Results Total of 23.39% CKD patients were reversed dipper BP pattern, 46.95% patients were non?dipper BP pattern, and dipper BP pattern was only 27.15%. Compared with dipper and non?dipper BP pattern group, patients with reversed dipper BP pattern had higher left ventricular mass index (LVMI), lower estimated glomerular filtration rate (eGFR) and severely damaged left ventricular diastolic function (all P<0.0083). After multiple linear regression analysis, reversed dipper BP pattern was an independent predictor for determining eGFR and LVMI. Age, lower hemoglobin and combination of diabetes were independently associated with reversed dipper BP pattern. Conclusion Reversed dipper BP pattern is common in Chinese CKD patients, which is closely related to renal damage and cardiovascular injuries.

AIM: To investigate the expression of osteopontin (OPN) and CD44 in human renal proximal tubular epithelial cells stimulated by human serum albumin (HSA). METHODS: Proximal tubular epithelial HK-2 cells were stimulated by HSA at different concentrations for different time, then OPN mRNA production was detected by RT-PCR, and OPN protein was detected by Western blotting. The expression of OPN and CD44 in HK-2 cells after stimulation for 24 h or 48 h were detected by immunofluorescence with confocal laser scanning microscope. RESULTS: Osteopontin mRNA in HK-2 cells showed a highest expression at 3 h and 48 h after HSA stimulation. However, the expression of OPN protein in HK-2 cells reached the maximum at 24 h after HSA stimulation. OPN mRNA and protein showed a strong dose-dependence relation with the concentration of HSA. HSA also stimulated HK-2 cells to express CD44 protein, the fluorescence of CD44 was most prominent at 48 h after HSA stimulation. CONCLUSION: HSA stimulates human renal proximal tubular epithelial cells to express OPN and CD44.

[Objective] To investigate the effects and mechanisms of Nrf2-ARE (nuclear factor erythroid-2 related factor-anti-oxidant response element) pathway on uremic serum-mediated endothelial dysfunction in human aortic endothelial ceils.[Methods] Human aortic endothelial cells were incubated in endothelial cell medium containing 10％ normal serum,10％ non-diabetic nuremic serum or 10％ diabetic uremic serum respectively,and 20 μmol/L tertiary butyl hydroquinone (tBHQ) were pretreated with cells to active Nrf2-ARE pathway.The cells apoptosis rate were measured by flow cytometry,and the synthesis of NO was detected by flow cytometry and immune fluorescent confocal,while the expression of P-eNOSer1177/eNOS,and quinone oxidoreductase-1 (NQO1) were measured by western blotting.The levels of malondialdehyde,superoxide dismutase,eatalase,and glutathione in these cells were also measured with kits.[Results] Aortic endothelial cells incubated with uremic serum had a higher level of apoptosis rate and MDA (P ＜ 0.05),and a lower level of NO systhesis,P-eNOSSer1177/eNOS expression,CAT,SOD,GSH (P ＜ 0.05).Pretreated with tBHQ can reduce the apoptosis rate and MDA level (P ＜ 0.05),improve the amount of NO systhesis,the expression of P-eNOSSer1177/eNOS,the levels of CAT,SOD,and GSH in these cells (P ＜ 0.05).[Conclusion] Activation of Nrf2-ARE pathway can improve endothelial dysfunction in aortic endothelial cells induced by uremic serum,and its mechanism might be related with enhancement of the antioxidant stress.

Objective To identify the risk factors associated with cardiovascular and cerebrovascular disease (CCVD) in maintenance hemodialysis (MHD) patients. Methods We analyzed all of the patients undergoing maintenance hemodialysis in the dialysis center of the 3rd Affiliated Hospital of Sun Yat-sen University for at least 3 months from Jan 1st, 2009 to Dec 31st, 2014. Baseline and yearly interval clinical data were recorded and patients were followed up until morbidity or death of CCVD. Cox proportional hazard regression and time-dependent Cox regression were used to estimate the relative risk of outcomes associated with clinical measurements. Results There were 243 patients enrolled in the study, with a mean age of (53.2 ± 16.4) years old, and 138 of them were male (56.8%). The multivariate Cox proportional model revealed that age (HR=1.040, 95%CI:1.015-1.065, P=0.002), Erythropoietin (EPO) dose (HR=0.914, 95%CI: 0.846-0.987, P=0.022) and history of cardiovascular and cerebrovascular disease (HR=4.045, 95%CI: 2.074-7.890, P<0.001) were independent predictors of CCVD in MHD patients. After adjusting for baseline predictors, time-dependent serum phosphorus level (HR=1.722, 95%CI: 1.034-2.866, P=0.037) was significantly associated with CCVD. Conclusion Older age, decreases in EPO dose and history of cardiovascular and cerebrovascular disease were associated with increased risks of CCVD in MHD patients. Increase in serum phosphorus level was associated with increased risks of CCVD in a time-dependent manner.

Objective To investigate whether high glucose can induce endothelial-mesenchymal transition (EndMT) in glomerular endothelial cells and the role of TGF-β in the process.Methods Rat glomerular endothelial cells were divided into five groups:normal glucose (NG,5.5mmol/L),high glucose (HG,15,30 mmol/L),TGF-β inhibition (HG+ LY36,30 mmol/L glucose + 10 μmol/L LY364947),hyperosmotic control (M,5.5 mmol/L glucose+25.5 mmol/L mannitol) and solvent control (D,5.5 mmol/L glucose + 1 ml/L DMSO).Western blotting was performed to detect relative protein quantities of endothelial marker claudin 5 and mesenchymal marker α-smooth muscle actin (α-SMA).TGF-β1 and TGF-β2 mRNA levels were measured by real-time PCR.Vascular endothelial marker VE-cadherin and mesenchymal marker α-SMA were detected by immunofluorescent stain and observed by confocal microscopy.Results Compared with NG,the expression of claudin5 protein in HG (15 or 30 mmol/L) was up-regulated while expression of α-SMA protein was down-regulated (P ＜0.05).Both TGF-β1 and TGF-β2 mRNA levels increased as well (P ＜ 0.05).However,when compared with HG,the claudin 5 levels increased while α-SMA decreased in TGF-β inhibition group.No significant changes were observed in hyperosmotic or solvent control group.Confocal microscopy showed the transformation of cells from a cobblestone-liked shape to a spindle one,and a decreasing expression of VE-cadherin while an increasing α-SMA in HG group (P ＜ 0.05),whereas TGF-β inhibition partly attenuated those changes in both morphological and protein levels.Conclusions High glucose treatment of glomerular endothelial cells results in an increase in the level of TGF-β1 and TGF-β2 mRNA and leads to endothelial-mesenchymal transiton.Inhibition of TGF-β partly prevents this process,indicating that TGF-β plays a crucial role in high-glucose-induced glomerular endothelial-mesenchymal transiton.

Objective To explore the features and influencing factors of ambulatory blood pressure in chronic kidney disease (CKD) patients.Methods A total of 540 CKD patients from May 2010 to May 2012 in our department were enrolled in this study.Ambulatory blood pressure monitoring was carried out.Blood pressure (BP),proteinuria and other clinical parameters were measured regularly.Ultrasonography was used to evaluate cardiac structure and function,carotid intima-media thickness and plaque.Univariate and multivariate analysis were used to examine the association between BP and clinical parameters.Results 63.9％ of CKD patients was non-dipper BP pattern,and 36.1％ was dipper BP pattern.As compared to dipper BP patients,those with non-dipper BP had higher ratio of nighttime/daytime proteinuria (0.51±0.29 vs 0.42±0.21,P ＜ 0.01),lower estimated glomerular filtration rate (eGFR) [(56.2±48.2) vs (75.5±56.5) ml· min 1 · (1.73 m2)-1,P ＜ 0.01],higher serum cystatin C[(2.8±2.0) mg/L vs (2.1±2.0) mg/L,P ＜ 0.01],higher left ventricular mass index [(53.7±23.2) vs (45.1± 16.3) g/m2,P ＜ 0.01] and severely damaged left ventricular diastolic function and higher carotid intima-media thickness [(0.7±0.3) vs (0.6±0.2) mm,P＜ 0.01].Nighttime blood pressure was independent predictor for proteinuria,eGFR and left ventricular mass index.Conclusions Nondipper blood pressure pattern is very common in CKD patients.Nighttime pressure is closely associated to renal damage and cardiovascular injuries.

Objective To analyze the prevalence,risk factors of kidney disease in type 2 diabetic patients with KDIGO classification of chronic kidney disease,also to study cardiovascular and cerebrovascular diseases and death in these patients,so as to investigate the significance of the KDIGO classification system.Methods One thousand six hundred and forty-five type 2 diabetic patients who were in hospitalization from June 2008 to December 2012 were grouped according to the KDIGO classification of chronic kidney disease and the incidence of vascular disease was analyzed based on the classification.Clinical features were compared between patients with or without kidney disease.The risk factors of kidney disease and the death of diabetic patients were also investigated.Results There were 915 male and 730 female,aged a median (57.86±12.54) years with (6.35±6.30) years duration of diabetes mellitus among the 1645 cases,and 37.2％ of patients had concomitant kidney disease.According to the classi fi cation of CKD,patients in CKD group 3a,group 3b and CKD group 4-5 accounted for 5.7％,3.5％ and 7.6％,while 33.4％ of patients had proteinuria,among which 19.5％ with microalbuminuria,13.5％ with macroalbuminuria.On complications,patients with hypertension accounted for 49.5％,hyperlipidemia 67.7％,diabetic retinopathy 27.4％,cardiovascular and cerebrovascular diseases 18.5％ (coronary artery disease 16.5％,cerebrovascular diseases 8.8％).Statistical difference was detected in the incidence of diabetic retinopathy,coronary artery disease and cerebrovascular diseases between CKD group 3a and 3b (P ＜ 0.05).The duration of diabetes,concomitant hypertention especially with elevated systolic blood pressure,diabetic retinopathy and hyperuricemia were the independent risk factors for type 2 diabetic patients with kidney disease.Age,Scr,complicating cardiovascular and cerebrovascular diseases and advanced CKD stage were the independent risk factors for the death of type 2 diabetic patients with kidney disease.Conclusion KDIGO classification of chronic kidney disease enables better staging of kidney diseases in diabetic patients for management and prognosis.Diabetic patients have a higher prevalence of renal diseases and cardiovascular and cerebrovascular events than the general population.Early control of factors such as blood pressure and serum uric acid can delay the progression of kidney disease,and the predictive role of diabetic retinopathy should be emphasized.