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国家重点基础研究发展计划(2012CB517600)

作品数:9 被引量:86H指数:5
相关作者:陈楠刘章锁杨柳刘东伟王沛更多>>
相关机构:上海交通大学医学院附属瑞金医院郑州大学郑州大学第一附属医院更多>>
发文基金:国家重点基础研究发展计划国家自然科学基金更多>>
相关领域:医药卫生农业科学轻工技术与工程理学更多>>

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KDIGO指南解读:成人微小病变肾病和特发性局灶节段性肾小球硬化治疗被引量:10
2012年
微小病变肾病(MCD)和特发性局灶节段性肾小球硬化(FSGS)是成人肾病综合征的常见病理类型。2012年6月发表的改善全球肾脏病预后组织(KDIGO)指南对多种原发及继发性肾小球肾炎的治疗给出了最新意见,对初发、复发、激素依赖和激素抵抗型MCD和FSGS患者的激素使用剂量、疗程及一线免疫抑制剂的选择等给予了建议。本文结合中国患者的特点对该指南关于MCD和FSGS治疗的建议做一解读。
陈楠任红
关键词:肾小球肾炎微小病变肾病局灶节段性肾小球硬化
Retrospective study of mycophenolate mofetil treatment in IgA nephropathy with proliferative pathological phenotype被引量:7
2014年
Background Mycophenolate mofetil (MMF) and cyclophosphamide (CTX) are widely used in treating various kidney diseases.However,whether they are effective and which one is better for treating IgA nephropathy patients with proliferative pathological phenotype in renal diseases,such as endocapillary proliferation,cellular crescents,and/or capillary loops fibrinoid necrosis is still unknown.We,therefore,initiated a study to compare the effects of MMF and CTX in treating IgA nephropathy with the above pathological lesions.Methods One hundred and nineteen patients with IgA nephropathy who had at least one of the three aforementioned lesions were enrolled.All patients were treated with prednisone; 48 patients received prednisone only (Pred group),40 received MMF and prednisone (MMF + Pred group),and 31 were treated with CTX and prednisone (CTX + Pred group).The median time of follow-up was 30 months (maximum:96 months).The primary endpoint was defined as renal survival.The incidence of remission of proteinuria was the secondary endpoint.Results Serum creatinine in all groups declined significantly at different follow-up times (P=0.002),and the differences among the three groups were significant (P<0.001).At 24 months of follow-up,the decline rates were 12.35%,32.95%,and 24.14% in the Pred,MMF + Pred,and CTX + Pred groups respectively.For urine protein excretion,the decline rates were 49.12% (Pred),73.67% (MMF + Pred),and 63.53% (CTX + Pred) respectively at 24 months of follow-up.The differences among the three groups were not significant (P=0.714).Renal survival (the primary endpoint) was significantly different (P=0.027); however,the sencondary endpoint was similar for all the three groups (P=0.100).Conclusions For IgA nephropathy patients with endocapillary proliferation,cellular crescents,and/or fibrinoid necrosis of capillary loops,prednisone combined with MMF was more effective in lowering the serum creatinine than with CTX.Combi
Liang Yan Zhang Junjun Liu Dongwei Quan Songxia Xing Guolan Liu Zhangsuo
关键词:CYCLOPHOSPHAMIDEPROTEINURIA
局灶节段性肾小球硬化患者致病基因突变检测被引量:2
2014年
目的对散发性或家族性局灶节段性肾小球硬化(focal segmental glomerulosclerosis,FSGS)患者进行FSGS致病基因热点突变进行筛查,了解这些热点突变在我国FSGS患者的发生情况。方法研究对象为我院经肾脏活检确诊的40例FSGS散发病例及一个22人的FSGS家系LF-01。收集散发病例的外周血,采用盐析法提取基因组DNA;对LF-01家系进行调查,收集实验室检测数据,并留存外周血提取基因组DNA。对40例散发病例及所有家系成员进行ACTN4第8外显子,TRPC6第2、5、12、13外显子和INF2基因2、3、4外显子筛查,通过PCR扩增外显子后,直接测序进行基因突变检测。结果LF-01家系共9人为患病或可能患病状态,该家系表现为不完全外显遗传模型。40例散发FSGS患者,平均发病年龄37岁,男女比例为26:14,其中22例患者临床表现为肾病综合征。我们对所有样本进行了ACTN4第8外显子,TRPC6第2、5、12、13外显子和INF2基因2、3、4外显子筛查,均未发现有已知的基因突变。结论国外报道的FSGS致病基因的热点突变ACTN4、TRPC6和INF2可能不是中国汉族人群FSGS的致病基因。
陈亭宇李贵森
关键词:局灶节段性肾小球硬化家族性基因
二甲苯体外诱导肾小管上皮细胞损伤的表观遗传机制
2015年
目的:研究二甲苯诱导肾小管上皮细胞损伤的特点及表观遗传机制。方法:不同浓度的二甲苯分别作用于体外培养的人肾小管上皮细胞(HK-2),通过ELISA法检测肾小管上皮细胞培养上清中中性粒细胞明胶酶相关脂质运载蛋白(NGAL)表达变化,流式技术检测肾小管上皮细胞凋亡,Caspase-3活性检测试剂盒检测Caspase-3活性。采用人甲基化450K芯片和焦磷酸测序对二甲苯诱导损伤的肾小管上皮细胞DNA的CG位点进行甲基化筛选和验证。结果:二甲苯诱导刺激后HK-2细胞NGAL表达增加,呈现剂量和时间依赖性;1.4mmol/L二甲苯作用48h后培养上清中NGAL的值较对照组显著增加[(4.52±0.49)pg/ml vs(2.30±0.11)pg/ml,P<0.01]。随加入二甲苯浓度的增加,HK-2细胞的凋亡比例和Caspase-3活性明显增加。甲基化芯片分析结果显示,二甲苯刺激后,HK-2细胞有243条探针甲基化出现显著差异,其中109条探针显示为甲基化水平增高,134条探针显示为甲基化水平降低,共涉及到138个基因。其中,细胞凋亡相关的基因(如Bax、FAF1等)出现了明显的甲基化改变,FAF1甲基化水平降低,Bax甲基化水平升高。焦磷酸测序的分析结果显示,二甲苯刺激后Bax基因(92%)的甲基化水平与对照组(85%)相比出现7%的甲基化改变;FAF1基因的甲基化水平比对照组降低6%,其甲基化改变的趋势与芯片结果相一致。结论:二甲苯刺激可引起HK-2细胞的损伤和凋亡增加,Bax、FAF1等凋亡相关基因的甲基化水平改变可能参与二甲苯对肾小管上皮细胞损伤,其机制有待进一步研究。
曹香华秦卫松徐忠秀陈朝红郑春霞曾彩虹刘志红
关键词:二甲苯肾小管上皮细胞中性粒细胞明胶酶相关脂质运载蛋白DNA甲基化
膜性肾病流行病学研究进展被引量:34
2016年
膜性肾病(membranous nephropathy,MN)是中老年人肾病综合征常见的病理类型之一。MN自然病程预后差异较大,约三分之一的患者可出现自发性缓解,然而仍有30%-40%的患者疗效不佳,在5—15年内进展至终末期肾脏病。随着肾穿刺活检技术和登记系统的普及和发展,MN流行病学特点逐渐被认知,多项调查显示,MN发病率呈上升趋势。为系统的了解MN流行病学,我们对近年来国内外MN流行病学的相关文献进行综述,以全面揭示MN流行病学特征,为MN的防治提供数据支持。
杨柳刘东伟刘章锁
关键词:流行病学特点膜性肾病终末期肾脏病穿刺活检技术流行病学特征病理类型
Association between dyslipidemia and chronic kidney disease: a cross-sectional study in the middle-aged and elderly Chinese population被引量:10
2013年
Background Dyslipidemia, a well-known risk factor for cardiovascular disease, is common in patients with kidney disease. Recent studies discerned that dyslipidemias play a critical role in renal damage progression in renal diseases, but the association between dyslipidemias and chronic kidney disease (CKD) in the general population remains unknown. Thus, we assessed whether the growing prevalence of dyslipidemia could increase the risk of CKD.Methods A total of 4779 middle-aged and elderl-yparticipants participated in this study. Dyslipidemias were defined by the 2007 Guidelines in Chinese Adults. Incident CKD was defined as albuminuria and/or reduced estimated glomerular filtration rate (eGFR, 〈60 ml.minl^-1.73 m^2). Regression analysis was used to evaluate the association between dyslipidemia and albuminuria/reduced eGFR.Results Participants with hypercholesterolemia exhibited a greater prevalence of albuminuria and reduced eGFR (10.0% vs. 6.1%, P=0.001; 4.0% vs. 2.4%, P=0.028, respectively). Both hypercholesterolemia and low high density lipoprotein cholesterol (HDL-C) were independently associated with albuminuria (odds ratio (OR) 1.49; 95% confidence interval (CI) 1.08-2.07 and OR 1.53; 95% CI 1.13-2.09, respectively). The multivariable adjusted OR of reduced eGFR in participants with hypercholesterolemia was 1.65 (95% CI 1.03-2.65). As the number of dyslipidemia components increased, so did the OR of CKD: 0.87 (95% CI 0.65-1.15), 1.29 (95% CI, 0.83-2.01), and 7.87 (95% CI, 3.75-16.50) for albuminuria, and 0.38 (95% CI 0.21-0.69), 1.92 (95% CI 1.14-3.25), and 5.85 (95% CI 2.36-14.51) for reduced eGFR, respectively.Conclusions Our findings indicate that dyslipidemias increase the risk of CKD in the middle-aged and elderly Chinese population. Hypercholesterolemia plays an important role in reducing total eGFR. Both low HDL-C and hypercholesterolemia are associated with an increased risk for albuminuria.
LIU Dong-weiWAN JiaLIUZhang-suoWANG PeiCHENG Gen-yangSHI Xue-zhong
关键词:DYSLIPIDEMIA
N端脑钠肽前体在维持性血液透析患者非显性水肿容量负荷评估中的意义被引量:18
2014年
目的 探讨N端脑钠肽前体(NT-proBNP)在评估维持性血液透析患者容量状态中的临床应用价值.方法 选择非临床显性水肿的维持性血液透析患者145例为研究对象.采用生物电阻抗方法检测患者多余细胞外液(Overhydration,OH值),胶体金法检测血浆NT-proBNP水平.按△OH水平(△OH=OH值-体重增加量)将患者分为容量超负荷组(H组,90例)、干体重达标组(N组,36例)和低干体重组(L组,19例).同期检测患者透析前血压、体质量增加值、Hb、Alb、BUN、Scr等指标.调整H组患者干体重,观察3月内患者容量负荷变化对血浆NT-proBNP水平的影响.结果 (1)126例患者NT-proBNP基线水平均高于正常范围.H组NT-proBNP中位数[M(1/4,3/4)]为1318.50 (717.00,3154.25) pg/ml;N组为703.50(873.00,450.50) pg/ml.基线NT-proBNP水平与△OH值呈正相关(r=0.801,P< 0.001).(2)3月后H组患者OH值及NT-proBNP均较调整前明显下降.其中41例患者干体重达标(H1组),NT-proBNP中位值为685.00 (422.50,988.50) pg/ml,△OH(0.63±0.23)L;49例患者持续未达标(H2组),NT-proBNP中位值为1569.00 (982.50,2500.50) pg/ml,△OH (1.75±0.71)L.两组间△OH和NT-proBNP的比较差异有统计学意义(均P<0.05).△OH和NT-proBNP呈正相关(r=0.684,P< 0.001).(3)当以△OH绝对值≤1定义干体重达标时,NT-proBNP在判断患者容量状态的受试者工作曲线(ROC)下面积(AUC)为0.818,95%可信区间0.733~0.904 (P< 0.001).NT-proBNP判断维持性血液透析患者容量状态的最佳临界值为962.50pg/ml,诊断的灵敏度为79.6%,特异度为73.2%.结论 维持性血液透析患者NT-proBNP水平升高.临床非显性水肿患者血NT-proBNP水平升高提示容量增加,可作为早期干体重调整的临床指标.
梁献慧王沛殷瑶瑶王瑞敏陆晓青刘章锁
关键词:血液透析电阻抗干体重N端脑钠肽前体
丙硫氧嘧啶诱发抗中性粒细胞胞质抗体相关性血管炎特点被引量:1
2015年
丙硫氧嘧啶( propylthiouracil,PTU)作为抗甲状腺药物在临床上应用已达半个多世纪,广泛用于治疗Graves病(毒性弥漫性甲状腺肿)及其他甲状腺功能亢进性疾病。PTU在治疗疾病的同时还可诱发一些不良反应,除可致红斑和荨麻疹等皮肤反应、关节疼痛和消化道不适等轻度症状,部分患者还可出现粒细胞缺乏、肝损害和抗中性粒细胞胞质抗体( antineutrophil cytoplasmic antibody,ANCA )相关性血管炎( ANCA-associated vasculitis,AAV)而危及生命。
陈永熙陈楠
关键词:抗中性粒细胞胞质抗体丙硫氧嘧啶PROPYLTHIOURACIL血管炎毒性弥漫性甲状腺肿甲状腺功能亢进性
丙硫氧嘧啶诱发抗中性粒细胞胞质抗体相关性血管炎机制被引量:5
2015年
抗中性粒细胞胞质抗体( antineutrophil cytoplas-mic antibody,ANCA)相关性血管炎( ANCA-associat-ed vasculitis,AAV)是一类主要累及小血管壁、以血管壁纤维素坏死样炎性反应为主要病理特征、血清ANCA检测呈阳性的免疫异常疾病。AAV 主要包括显微镜下多血管炎、肉芽肿性多血管炎、嗜酸性肉芽肿性多血管炎及肾脏局限性血管炎。
李欣陈楠
关键词:显微镜下多血管炎抗中性粒细胞胞质抗体丙硫氧嘧啶ANCA肉芽肿性病理特征
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