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    临床研究

  • PENG Yan;ZHANG Wei;HAO Jing;XU Qi;LUO Mei-ping;YUAN Wei-jie
    2010, 26(2): 81-85.
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    Objective To study the association of fibroblast growth factor 23 (FGF23) with calcium(Ca)-phosphorus (P) metabolism and renal function in patients with chronic kidney disease (CKD). Methods Serum samples of 20 healthy people and 72 CKD patients were collected. Patients were divided into five groups according to renal function. Levels of FGF23,25(OH)VitD3, and 1,25(OH)2VitD3 were measured by ELISA. Intact parathyroid hormone (iPTH) was detected by immunoradiometric assay. Scr, BUN, calcium(C), phosphorus(P) and albumin were assessed by autobiochemistry machine. Results Levels of serum FGF23, P, iPTH increased gradually and 1,25(OH)2VitD3 decreased with the decline of renal function, especially in stages 4-5 of CKD, whose differences were significant. Pearson correlation analysis revealed, during CKD1-5 stages, logFGF23 was correlated with P, logiPTH, GFR, 1,25(OH)2VitD3 (r=0.653, P<0.01; r=0.800, P<0.01; r=-0.753, P<0.01; r=-0.265, P<0.05). During CKD1-3 stage, logFGF23 was positively correlated with logiPTH (r=0.374, P<0.05) and not correlated with P, GFR, 1,25(OH)2VitD3. During CKD4-5 stages, logFGF23 was positively correlated with P, logiPTH (r=0.381, P<0.05; r= 0.515, P<0.01) and negatively correlated with GFR (r=-0.654, P<0.01). There were no correlations of logFGF23 with 25(OH)VitD3 and Ca. Conclusions Levels of serum FGF23, P, iPTH increase and 1,25(OH)2VitD3 decreases with the decline of renal function, especially during CKD4-5 stages. The level of FGF23 is associated with iPTH during CKD1-3 stage. When GFR<30 ml/min, FGF23 level is affected by renal function, phosphorus and iPTH.
  • JIANG Lan*;LIU Quan-ying;CHENG Li-tao;ZHU Xiang-ming;WANG Tao
    2010, 26(2): 86-90.
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    Objective To evaluate the clinical value of a new non-invasive and quantitative index overhydration (OH) in hydration status assessment for peritoneal dialysis (PD) patients. Methods Eighty peritoneal dialysis patients were enrolled in this study. Overhydration was measured by electrical bioimpedance measurement. Echocardiography was also performed at the same time. Linear regression and correlation analysis were carried out between OH and echocardiographic indicators. Cardiac status of patients with high-OH(OH≥2 L) and low-OH (OH<2 L) value was also compared. Results In these 80 PD patients, OH was positively correlated with EDV, ESV, LVEDD, LA, LVM, LVMIBSA, LVMIheight (all P<0.01). The adjusted RR was 0.21, 0.27, 0.14, 0.12, 0.26, 0.25 and 0.20, respectively. There were no significant differences in gender, age, height, weight, dialysis duration, BMI, Kt/V between high-OH and low-OH patients. The SBP, DBP, PP, MAP were high in high-OH group as compared to low-OH group (P<0.01). LVEF, LVFS, SV, CO, CI, E peak, A peak, E/A did not differ between two groups. Cardiac structure and hemodynamic parameters, such as ESV, LVEDD, RV, LA, VTI, AV max, were higher in high-OH group as compared to low-OH group (P<0.05), while no significant difference of TPR and TPRI between two groups was found. Left ventricular remodeling indicators, such as IVS, LVPW, LVM, LVMIBSA, LVMIheight, LVHBSA and LVHheight, were higher in high-OH group than those in low-OH group (P<0.05). Conclusion OH as a novel marker in hydration status assessment is closely correlated with cardiac structure, which may be used as a non-invasive quantitative indicator of fluid status in PD patients.
  • WANG Xiao-qin*;WANG Chang-jiang;YUAN Jun;YIN Ping
    2010, 26(2): 91-94.
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    Objective To evaluate the efficacy and side effects of mycophenolate mofetil (MMF) in the treatment of idiopathic membranous nephropathy (IMN). Methods Randomized controlled trials (RCTs) and clinical controlled trials(CCTs)were used for the meta-analysis. Electronic and manual retrieval from Pubmed-Medline, EMBASE and Cochrane Library Database were performed to identify RCTs or CCTs in which MMF was compared with other regimes in treating IMN. Efficacy and side effects data were extracted and summarized with fixed effect model odds ratio (OR) or risk ratio (OR). Results Three RCTs and one CCT with 141 patients were enrolled in the study. In 3 RCTs, MMF was compared with cyclophosphamide (CTX), conservative treatment(non-immunosuppressive)and chlorambucil respectively. In the CCT, MMF was compared with cyclophosphamide. Compared with control groups, MMF did not significantly increase the complete remission (OR=0.74, 95%CI=0.32-1.75) and partial remission (OR=0.56, 95%CI=0.28-1.11). The overall response rate of MMF therapy was significantly lower than that of control groups(OR=0.46, 95%CI=0.23-0.92). There was no significant difference in infection, gastrointestinal symptoms or anemia among the patients receiving MMF and the patients receiving other immunosuppressive agents, but MMF reduced the incidence of leucopenia obviously (OR=0.06, 95%CI=0.01-0.41). Conclusion Mycophenolate mofetil should not be recommended as the first- line therapy for IMN.
  • ZHOU Xiao-ling;HAN Qing-feng;FU Gang
    2010, 26(2): 95-98.
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    Objective To evaluate the efficiency of cefazolin plus ceftazidime and vancomycin plus ceftazidime as initial therapy for peritoneal dialysis(PD)-related peritonitis. Methods Retrospective analysis of 90 PD-related peritonitis from January 2006 to May 2009. Thirty-seven episodes were treated with cefazolin plus ceftazidime(CC group), and 97 episodes with vancomycin plus ceftazidime (VC group). Primary efficiency, outcomes, pathogenesis and resistance were analyzed respectively. Results The primary efficiency of CC group and VC group was 81.1% and 86.2%, respectively (P>0.05). Gram-positive organisms of CC group and VC group was 56.8% and 50.5%, respectively (P>0.05). The cure rate was 91.9% in CC group and 97.9% in VC group (P>0.05). Conclusion Cefazolin plus ceftazidime and vancomycin plus ceftazidime have similar efficiency as an initial therapy for PD-related peritonitis.
  • WEN Ji-lan*;WANG Feng-xian;LI Bing-cheng;LI Rong-shan;SHI Yuan-yuan;WANG Su-ping.
    2010, 26(2): 99-104.
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    Objective To investigate the prevalence of urban adult chronic kidney disease (CKD) and influential factors in Youyu county of Shanxi province in order to provide evidences for the treatment and prevention of CKD. Methods A total of 3603 residents aged ≥18 years old in Youyu county were selected by random cluster sampling. They were interviewed with questionnaire and tested for albuminuria, haematuria and renal function. Associations among demographic characteristics, health characteristics (eg. overweight or obesity, hypertension, glycometabolism abnormity) and indicators of kidney damage were examined. Results (1) Eligible data of 3502 subjects were enrolled in the study. After adjustment for age and gender, the prevalence of albuminuria, haematuria and reduced estimated glomerular filtration rate (eGFR) was 6.8% (95%CI:6.5%-7.1%), 7.1% (95%CI:6.8%-7.4%) and 2.0% (95%CI:1.8%-2.2%), respectively. Approximately 15.1% (95%CI:14.5%-15.5%) subjects had at least one indicator of kidney damage. The awareness rate of CKD was 6.9%. (2)Female had higher prevalence of albuminuria, hematuria and reduced eGFR than male (P<0.01). (3)Albuminuria, reduced eGFR and CKD prevalence increased with age no matter male or female (P<0.01), but overall prevalence of hematuria was not associated with age. (4)Albuminuria was independently associated with gender, glycometabolism abnormity, hyperlipidemia, kidney disease history and the history of cardiovascular disease. Reduced eGFR was independently associated with gender, age, hypertension, glycometabolism abnormity, kidney disease history, family history of kidney disease, and microalbuminuria. Haematuria was independently associated with female. Conclusions The prevalence of adult CKD is quite high in Youyu county of Shanxi province, and the risk factors are similar to that of domestic well-developed cities and western countries. It shows a more urgent need for CKD prevention and control work in the economic underdeveloped areas.
  • GAO Dan*;LIU Zhang-suo;ZHAO Zhan-zheng;LIANG Xian-hui;LI Yan.
    2010, 26(2): 105-109.
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    Objective To examine the expression of vascular endothelal growth factor (VEGF) and endostatin (ES) in human peritoneum and to investigate its effect on peritoneal neoangiogensis. Methods Peritoneal samples were obtained from healthy subjects (n=8), uremic predialysis patients (n=12) at catheter insertion and peritoneal dialysis (PD) patients (n=10) at the time of catheter remove, reinsertion or renal transplantation. Immunohistochemical staining and RT-PCR technique were used to examine VEGF and ES expression in peritoneal tissue. Microvessel density (MVD) of peritoneal tissue was assessed using immunohistochemistry with CD34 monoclonal antibody. Results All the peritoneal samples expressed VEGF and ES at both protein and mRNA level. VEGF mRNA and protein expression in uremic predialysis and PD group were significantly up-regulated as compared to healthy group (0.47±0.01, 0.62±0.02 vs 0.74±0.02; 95.673±2.01, 117.126±2.07 vs 140.184±2.25, all P<0.05). ES protein was up-regulated in above two groups (94.902±2.38, 113.380±2.33 vs 145.489±3.05, all P<0.05), but ES mRNA did not change obviously as compared to healthy group. MVD was up-regulated in uremic predialysis and PD group as compared with healthy group(3.05±0.45, 5.98±0.47 vs 9.62±0.49, all P<0.05). Conclusion Uremia circumstances and non-physiological compatibility of peritoneal dialysis liquid increase VEGF and ES expression as well as MVD, which may play a role in neoangiogenesis of peritoneum.
  • 基础研究

  • WANG Rui;DING Guo-hua;LIANG Wei;CHEN Cheng;YANG Hong-xia
    2010, 26(2): 110-115.
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    Objective To investigate the effect of lectin-like oxidized low-density lipoprotein receptor 1(LOX-1) on tubular epithelial-myofibroblast transdifferentiation(TEMT) induced by oxidized-low density lipoprotein (ox-LDL) and to elucidate its possible mechanism. Methods NRK-52E cells were incubated with ox-LDL (0, 25, 50 and 100 mg/L) for 24 hours or pre-treated with the chemical blocker of LOX-1 receptor, polyI(250 mg/L)or carrageenan (250 mg/L ) or antioxidant- NAC,and then exposed to 50 mg/L ox-LDL. LOX-1 mRNA was examined by real-time PCR. LOX-1 and E-cadherin and α-SMA protein were assessed by Western blotting. Lipid deposit was examined by oil red O and ROS production was evaluated by confocal laser scanning microscopy. Results (1)ox-LDL increased the expression of LOX-1 mRNA and protein in dose-dependent manner from 0 mg/L to 100 mg/L. Following the increase of LOX-1, lipid intake, ROS generation and α-SMA expression were all increased, but E-cadherin was decreased. (2)Pre-treatment with Poly I or carrageenan significantly inhibited ox-LDL-induced LOX-1 expression (P<0.05), lipid intake (P<0.05) and ROS generation (all P<0.05), which were associated with the decrease of α-SMA expression and the increase of E-cadherin expression. (3)Pre-treatment with NAC also inhibited ROS generation (P<0.05), the expression of α-SMA and LOX-1 (all P<0.05), but increased the E-cadherin expression (P<0.05). (4)α-SMA expression was positively correlated with ROS generation(r=0.87, P<0.05), and E-cadherin expression was negatively correlated with ROS generation(r=-0.82, P<0.05). Conclusion ox-LDL can induce tubular epithelial-myofibroblast transdifferentiation through binding to LOX-1 and promoting ROS generation.
  • ZHANG Yu;ZHOU Jian-hua.
    2010, 26(2): 116-122.
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    Objective To investigte the effect of hepatitis B virus X protein (HBx) expressed in cultured mouse podocytes via adenoviral infection on cell proliferation and to elucidate its possible mechanism. Methods HBx gene was inserted into an adenovirus-based vector and transfected into mouse podocytes. Cell morphologic changes were investigated by staining with Wright-Giemsa. Cell growth was measured by MTT-assay and CFDA-SE proliferation assay. Cell cycle phase was demonstrated by flow cytometry, and the expression of specific cell cycle regulatory proteins was examined by Western blot analysis or flow cytometric bivariate analysis. Results The recombinant adenovirus Ad.HBx was generated successfully, which was confirmed by polymerase chain reaction and DNA sequencing. The expression of HBx protein in the Ad. HBx-infected podocytes was confirmed by Western blot. At day 5 post-infection, HBx-expressing podocytes presented the characteristics of mitotic catastrophe such as binuclei, multinuclei, and polymorphonuclei accumulation. MTT assay showed that the growth curve of Ad-infected podocytes was basically consistent with control, but both were significantly higher than that of Ad.HBx-infected podocytes after day 4 post-infection(P<0.01). Furthermore, CFDA-SE-based proliferation assay also revealed that at day 3 post-infection, the proliferation rate of HBx-expressing podocytes was significantly slower than that of Ad-infected podocytes and controls (proliferation index: 11.2 vs 15.4, 13.3), and this trend became much obvious with the time (proliferation index: 32.5 vs 61.6, 54.0). FACS analysis showed that with the HBx-induced G2/M phase arrest, the levels of cyclin B1 and CDK-inhibitor p21 were significantly increased in HBx-expressing podocytes, but the expression of cyclin A was slightly decreased. Conclusions Exogenous expression of HBx inhibits the growth of podocytes. This effect is mediated through the G2/M phase arrest associated with an increase of cyclin B1 and CDK-inhibitor p21 and a decreased expression of cyclin A. These events may partially explain the reduced podocyte number in hepatitis B virus-associated glomerulonephritis.
  • ZHOU Guang-yu*;MA Jian-fei;LI De-tian;LI Li-yan;LI Zhi-ming;WANG Li-ning.
    2010, 26(2): 123-127.
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    Objective To investigate the influence of peroxisome proliferators-activated receptor γ (PPARγ) ligands on the expression of connective tissue growth factor (CTGF) and plasminogen activator inhibitor 1 (PAI-1) in rat peritoneal mesothelial cells (RPMCs) induced by high glucose. Methods RPMCs were isolated, cultured, passaged, confirmed and divided into 4 groups: (1)treated with glucose for 24 h in the concentrations of 0.1%, 1.5%, 2.5% and 4.25%, respectively; (2)treated with 2.5% glucose for 0, 6, 12, 24, 36, 48 and 72 h respectively; (3)treated with mannitol for 24 h in the concentrations of 0.1%, 1.5%, 2.5% and 4.25%, respectively; (4)pretreated with pioglitazone (5, 15 μmol/L) and 15d-PGJ2 (5, 15 μmol/L) for 2 h respectively, then treated with 2.5% glucose for 24 h. The expression of CTGF and PAI-1mRNA was detected by RT-PCR. The expression of PPARγ, CTGF and PAI-1 protein was detected by Western blot. Results RPMCs expressed PPARγ in normal condition. Glucose reduced the protein expression of PPARγ in dose- and time-dependent manner (P<0.05 and P<0.01). Mannitol of different concentrations had no effect on the expression of PPARγ in RPMCs (all P>0.05). The mRNA and protein expression of CTGF was up-regulated significantly by stimulation of 2.5% glucose (P<0.01). Both 15d-PGJ2 and pioglitazone (5, 15 μmol/L) decreased the mRNA and protein expression of CTGF in concentration-dependent manner (P<0.05 and P<0.01). 2.5% glucose increased the mRNA and protein expression of PAI-1 (P<0.01). 5 μmol/L 15d-PGJ2 decreased the mRNA expression of PAI-1, but not protein. 15 μmol/L 15d-PGJ2 decreased the mRNA and protein expression of PAI-1 (P<0.05 or P<0.01). The mRNA and protein expression of PAI-1 alos down-regulated in concentration-dependent manner induced by pioglitazone (5, 15 μmol/L) (P<0.05 and P<0.01). Conclusions High glucose down-regulates the expression of PPARγ in RPMCs and this effect is not correlated with hyperosmosis. PPARγ ligands strongly inhibit CTGF and PAI-1 production in RPMCs induced by high glucose, which may be a novel approach to prevent peritoneal dialysis-related peritoneal fibrosis.