大鼠发育对肾脏MR表观扩散系数影响的实验研究

目的 探讨正常大鼠从幼鼠到成年的发育过程中,肾脏皮髓质表观扩散系数(ADC)值的变化.方法 对5只1个月龄的雄性Wistar大鼠分别在实验开始第1天(d1)、第5天(d5)、第10天(d10)、第30天(d30)和第50天(d50)在3.0 T MR上进行肾脏SE回波平面成像(EPI)序列扩散加权成像(DWI),扩散敏感因子(b值)选择0和500 s/mm2.测量右肾皮髓质ADC值,手工画出每层肾脏面积,计算其体积,采用配对t检验分析皮髓质间ADC值的差异,并采用重复测量方差分析评价大鼠肾脏体积及ADC值随大鼠发育的变化.结果 在b值为0和500 s/mm2时,除d1外,大鼠肾脏皮质ADC值均明显高于髓质(P＜0.01).随月龄增加,肾脏体积逐渐增大,从(0.86±0.02)mm3逐渐增加到(1.47±0.21)mm3.而皮髓质ADC值均随月龄而增加,皮质ADC值从(1.66±0.14)×10-3mm2/s逐渐增加至(1.96±0.08)×10-3mm2/s(P＜0.05);髓质ADC值从(1.54±0.12)×10-3mm2/s逐渐增加至(1.91±0.09)×10-3mm2/s(P＜0.05).结论 从1个月到3个月龄的大鼠,其肾脏皮髓质的ADC值是逐渐增加的.对大鼠肾脏疾病模型进行MR DWI研究时,需要考虑到所用大鼠不同发育阶段对ADC值的影响.     

存在肾小动脉微血管病变且非高血压IgA肾病患者的临床病理特点和预后分析

目的总结和分析非高血压的IgA肾病(IgA nephropathy,IgAN)合并肾小动脉微血管病变(microangiopathy,MA)患者的临床病理特点和预后。方法抽取北京大学第一医院IgAN前瞻性队列人群中非高血压成人患者,重新进行病理阅片,根据肾小动脉病变,分为MA组、动脉硬化病变(AS)组和无血管病变组,分析其临床病理及预后特点。复合肾脏终点事件包括终末期肾病或估算肾小球滤过率(eGFR)下降≥30%。采用Cox回归模型分析预后的危险因素。结果共420例IgAN患者被纳入本研究,其中37(8.8%)例患者合并MA,134(31.9%)例合并AS,其余249例无血管病变。相对于AS组或无血管病变组,合并MA的患者尿蛋白量更严重[1.47(1.08,2.84)g/d比1.31(0.68,2.56)g/d、1.04(0.55,2.00)g/d,P=0.002],肾功能更差[eGFR:(75.3±26.5)ml·min-1·(1.73 m2)-1比(85.7±27.0)ml·min-1·(1.73 m2)-1、(98.6±24.8)ml·min-1·(1.73 m2)-1,P<0.001],并有更高的节段性肾小球硬化和(或)球囊粘连(S1)、肾小管萎缩/间质纤维化(T1/2)、细胞/细胞纤维新月体病变(C1/2)比例(均P<0.05)。随访期间,合并MA的患者发生终点事件比例更高[54.1%比33.6%、32.9%,χ2=6.491,P=0.039]。Cox多因素分析模型显示,MA是IgAN发生进展的独立危险因素(HR=1.872,95%CI 1.044~3.357,P=0.035),而其他类型血管病变不影响预后。结论非高血压IgAN患者合并MA不少见,这提示高血压并非导致IgAN血管病变的唯一危险因素。     

汞中毒相关肾小球疾病的临床病理分析

Objective To elucidate the clinical and pathological characteristics of patients with mercury poisoning-associated glomerulonephropathy. Methods Seven patients with mercury poisoning-associated glomerulonephropathy were enrolled in this study. The pattern of mercury exposure, feature of mercury toxicity, and clinicopathological presentation of the kidneys were investigated. Results They were all female, averaged (28.9 ±8.1) years old. Skin-whitening cream was the only cause of mercury poisoning. Proteinuria occurred 5 to 8 months after exposure. Serum mercury were 27.0 to 98.0 μg/L, and spot urinary mercury were 34.4 to 204.0 μg/L. The presentation of all the patients was mild to moderate edema with proteinuria and decreased serum albumin level. Five patients (5/7) were diagnosed as nephrotic syndrome. Six patients underwent renal biopsy: 3 cases with minimal change disease, 2 cases with membranous nephropathy and 1 case with focal segmental glomerular sclerosis. All the patients were administrated chelation therapy with sodium dimercaptopropanal sulfonate or sodium dimercaptosuccinic acid for 3 to 7 courses. They got complete remission by 3 to 5 weeks treatment. Conclusions Patients in this study with glomerulonephropathy induced by mercury poisoning are all from skin-whitening cream exposure. Mild to moderate edema and proteinuria are the common clinical pattern. Minimal change disease, membranous nephropathy and focal segmental glomerular sclerosis are found pathologically. Chelation therapy is effective.     

经皮球囊扩张血管成形术治疗血液透析患者动静脉瘘功能不良

目的 观察经皮球囊扩张血管成形术(Percutaneous transluminal angioplasty,PTA)治疗血液透析患者动静脉瘘(arteriovenous fistula,AVF)功能不良的临床疗效.方法 自2010年1月至12月,对在北京大学第一医院肾内科因AVF功能不良行PTA治疗的患者行前瞻性的临床观察.总结患者的临床特点、血管造影结果和PTA治疗的技术指标、临床和技术成功率.术后对患者进行随访,观察AVF通畅率.结果 12例患者AVF狭窄均发生在吻合口附近,行PTA治疗的技术成功率91.7%(11/12).7例晚期功能不良病例临床成功率85.7%(6/7).术后随访8.6(3.3～14.8)个月,AVF1级通畅率为100%.5例AVF早期功能不良患者平均随访8.2(4.1～11.3)个月.1例在PTA术后3个月发生AVF再狭窄,余4例AVF成熟,透析中血流量达200ml/min以上.结论 PTA是治疗血液透析患者AVF功能不良的一个有效手段.     

加强少见肾脏病的临床与基础研究

改革开放30余年来,经几代肾脏病学者的艰苦努力和攀登,我国肾脏病事业取得了飞速发展,对常见的肾脏疾病、特别是肾小球疾病的诊治取得了长足的进步,某些研究领域己逐步与国际接轨。但基于我国肾脏病研究基础薄弱、地广人多,发展很不平衡,因此提升我国少见肾脏病的诊治水平尚有很大空间,加强少见肾脏病的临床和基础研究仍任重而道远。本文就如何提高我国少见肾脏病诊治水平提出几点看法：(1)认真做好肾活检病理检查,重视免疫病理和电镜在病理诊断中的作用。强调制片、染色质量,光镜、免疫荧光和电镜检查不应缺失任何一项,互为补充进行综合判断。提倡临床病理讨论会,病理学家与临床专家互动,是提高少见肾脏病诊断率和正确性的有效方法。(2)重视临床资料收集和分析,结合基因检测,提高少见肾脏病的诊断率,防止误诊、漏诊。重视病史(包括家族史)和临床资料(查体、实验室及相关医学影像检查结果)收集,并加以认真分析;在此基础上应努力开展与疾病相关的特殊检查,对于疑似遗传性肾病患者应做遗传基因检测,避免把少见的继发性肾脏病和遗传性疾病漏诊或误诊为原发性肾脏病。(3)对危害性大的少见肾脏病积极开展流行病学调查和发病机制的研究,以期深入阐明其发病机制。(4)组织好高水平临床治疗研究,以期获得高质量循证医学证据,指导和提高我国整体肾脏病的临床治疗水平。(5)强调依据患者具体病情制定个体化治疗方案和充分发挥中医中药优势,努力提高我国少见肾脏病的疗效。     

成年人肾小球基底膜厚度及基底膜变薄标准研究

Objective To elucidate the thickness of glomerular basement membrane (CBM) in adult kidney tissue and to establish the standard of GBM thickness for thin basement membrane nephropathy (TBMN) in China. Methods Kidney cortex tissue samples apart from cancer focus were collected from 29 patients undergoing nephrectomy. Clinical data of patients were analyzed. Light, immunofluorescence and electron microscope examinations were performed on these 29 samples to measure the thickness of GBM and the distribution of collagen Ⅳα3, α5 chains. Results There were fifteen male and fourteen female cases with age (55.9±14.9) (20-80) years old. No familial history of renal disease or other diseases was found in these cases. The CBM thickness of these samples was (363.6 ±46.8) nm, which was associated with gender. GBM thickness was (384.0±41.7) nm in male, and (335.0±39.2) nm in female, which was significantly different (P=0.008). The standard to diagnose thin GBM should be the mean minus double standard deviation. So the standard of GBM thickness for TBMN should be <270 nm. Conclusions The GBM thickness of adults is (363.6±46.8) nm. GBM thickness is associated with gender, which is thicker in males with significant difference. It is suggested that the standard of GBM thickness for TBMN in adult should be <270 nm, and the difference of GBM thickness between male and female should be considered too.     

尿Tamm-Horsfall蛋白水平联合尿液补体H因子水平和IgA肾病Haas分级及预后相关

目的探讨肾活检时尿Tamm-Horsfall蛋白水平联合尿补体H因子水平与Ig A肾病患者的组织学分型及预后的相关性。方法选择在在北京大学第一医院接受肾活检和规律治疗及随访的Ig A肾病患者351例。收集其基线临床病理资料,病理表现按照Haas分级进行打分。检测基线时尿TammHorsfall蛋白水平和尿补体H因子水平,分析该两种因子与临床,病理及预后的相关性。预后指标用肾脏终点事件表示,肾脏复合终点事件包括:(1)终末期肾脏病[估算肾小球滤过率(estimated glomerular filtration rate,e GFR)15m L/min?1.73 m2];(2)e GFR比初始下降≥50%;(3)血肌酐水平加倍。结果尿Tamm-Horsfall蛋白水平越低,同时补体H因子水平越高,Ig A肾病患者的24h尿蛋白定量越多(χ~2=37.899,P0.001),血白蛋白水平(χ~2=37.487,P0.001)、e GFR水平(F=16.333,P0.001)水平越低;同时,按照Haas分型的组织学损伤更严重(χ~2=52.304,P0.001),复合终点事件发生率更高(χ~2=35.678,P0.001)。Kaplan-Meier生存分析曲线显示,尿中补体H因子越高,同时Tamm-Horsfall蛋白越低,患者的预后越差(Log Rankχ~2=31.938,P0.001)。结论尿Tamm-Horsfall蛋白和尿补体H因子水平可联合预测是Ig A肾病患者的预后。尿液中补体H因子越高,尿Tamm-Horsfall蛋白水平越低,Ig A肾病患者的组织学Haas分型越严重,预后越差。     

尿调蛋白酶联免疫吸附试验检测方法的建立及其在IgA肾病中的应用

目的：建立尿尿调蛋白的酶联免疫吸附试验（enzyme-linked immunosorbent assays, ELISA）检测方法,并对IgA肾病患者的尿尿调蛋白水平监测进行进一步验证。方法：以多克隆抗体作为包被抗体,单克隆抗体作为检测抗体,建立尿调蛋白的快速双抗夹心检测方法,检测其精确性及重复性,随机选取55例尿液标本,同时以商品化试剂盒与本实验方法进行检测,比较166例IgA肾病患者和正常人的尿尿调蛋白水平。结果：获得的标准曲线为0.78~12.5 μg/L,实验室内变异系数为7.5%,实验室间变异系数为7.9%。55例尿液标本的商品化试剂盒与本实验方法结果比对,相关系数为r=0.615,P<0.001;166例IgA肾病患者的尿尿调蛋白/尿肌酐比值低于正常人。结论：尿尿调蛋白的ELISA检测方法灵敏,重复性较好,可运用于大样本的人群检测,IgA肾病患者的尿尿调蛋白分泌低于正常人。     

木通所致肾小管间质肾病及其临床病理特点分析

目的探讨木通及相关中成药物所致肾小管间质肾病(MT-TIN)的临床病理特点,初步分析影响肾功能的相关因素及预后.方法回顾性分析51例MT-TIN病人的临床及病理资料,根据病理分为急性、慢性轻型和慢性重型组,对临床和病理指标进行半定量及相关分析,探讨其服药与发病、临床病理、治疗与转归特点,并与抗菌药物所致急性肾小管坏死(A-ATN)或急性间质性肾炎(A-AIN)加以比较.结果MT-TIN以乏力、消化道症状、多尿及夜尿增多为主要临床症状,常有明显肾小管功能障碍并可伴肾小球功能异常,特征为无明显尿镜检异常,以及病变早期无贫血.主要病理特点为急性期肾小管上皮细胞严重变性、坏死、脱落,形成裸基底膜,细胞再生差,肾间质少有细胞浸润,纤维化病变出现早;慢性期肾小管逐渐萎缩,肾间质弥漫纤维化.病人血肌酐(Scr)增高,并与贫血及肾间质纤维化程度密切相关.经停药,多数病人在2个月内病情可稳定.MT-TIN病人的临床和病理特点均与A-ATN或A-AIN有明显不同;其多数与过量或长期间断应用木通煎剂及含关木通的中成药有关,少数病人常规用药也可发病.结论MT-TIN是一类特殊类型的药物性肾小管间质疾病,主要与应用木通类药物不当有关,应尽可能避免应用含马兜铃酸的木通类药物,并对用药病人加强监测.     

成年人肾小球基底膜厚度及基底膜变薄标准研究

Objective To elucidate the thickness of glomerular basement membrane (CBM) in adult kidney tissue and to establish the standard of GBM thickness for thin basement membrane nephropathy (TBMN) in China. Methods Kidney cortex tissue samples apart from cancer focus were collected from 29 patients undergoing nephrectomy. Clinical data of patients were analyzed. Light, immunofluorescence and electron microscope examinations were performed on these 29 samples to measure the thickness of GBM and the distribution of collagen Ⅳα3, α5 chains. Results There were fifteen male and fourteen female cases with age (55.9±14.9) (20-80) years old. No familial history of renal disease or other diseases was found in these cases. The CBM thickness of these samples was (363.6 ±46.8) nm, which was associated with gender. GBM thickness was (384.0±41.7) nm in male, and (335.0±39.2) nm in female, which was significantly different (P=0.008). The standard to diagnose thin GBM should be the mean minus double standard deviation. So the standard of GBM thickness for TBMN should be <270 nm. Conclusions The GBM thickness of adults is (363.6±46.8) nm. GBM thickness is associated with gender, which is thicker in males with significant difference. It is suggested that the standard of GBM thickness for TBMN in adult should be <270 nm, and the difference of GBM thickness between male and female should be considered too.