IgA肾病牛津分型与Hass分型临床意义的比较研究

目的探讨IgA肾病牛津病理分型与Hass分型方法的临床适用性。方法①收集经临床及肾活检病理证实的139例原发性IgA肾病患者尿蛋白定量(24 h)、计算估计肾小球滤过率(eGFR)和平均动脉压(MAP)。②按照IgA肾病牛津分型与Haas分型标准对139例患者的肾活检组织进行光镜下病理分型,比较牛津病理分类方法与Haas分型方法的临床适用性。结果①牛津病理分型单变量分析结果显示,不同系膜细胞增生评分组间(M0/1)尿蛋白定量(24 h)差异有统计学意义(P=0.043);不同肾小球节段硬化/球囊粘连积分组间(S0/1)eGFR差异有统计学意义(P=0.038),不同程度肾小管萎缩/间质纤维化组间(T0/1/2)尿蛋白定量(24 h)、eGFR和MAP差异有统计学意义(P=0.025,P<0.01,P<0.01)。②与Ⅰ型和Ⅱ型比较,Ⅳ型和Ⅴ型尿蛋白定量(24 h)和MAP明显增高,差异有统计学意义(P<0.05);与Ⅲ型比较,Ⅳ型、Ⅴ型患者eGFR明显减低,级间差异有统计学意义(P<0.05)。结论①IgA肾病牛津病理分型的4个病理指标与IgA肾病临床指标独立相关,能较客观地反映肾活检肾脏病变的动态变化。②Hass病理分型级数越高,临床肾功能指标越差,故临床适用性较强。     

青少年型IgA肾病的临床与病理探讨

目的通过对28例青少年型IgA肾病的临床与病理回顾性分析，观察IgA肾病的临床病理特点及其内在联系。方法经皮肾穿刺活检获得年龄在以18岁以下的IgA肾病患者的病理结果，并将I临床表现及病理结果进行分类分型，同时获取IgA肾病的病理资料。结果青少年型IgA肾病的临床表现以无症状血尿或尿液检查异常最常见，有16例（57．1％），其次为肾病综合征8例（28．6％）；病理类型以系膜增生性肾小球肾炎最常见，有15例（53．6％），其次为局灶节段增生性肾小球肾炎9例（32．1％）；临床表现为无症状性血尿或尿液检查异常和肾病综合征常见的病理类型为局灶增乍性肾小球肾炎及系膜增生性肾小球肾炎。病理特点以轻度系膜增生为主，慢性化表现少见。结论青少年型IgA肾病病理特点以轻度系膜增生常见，慢性化表现少见，病理类型以轻度系膜增生性肾小球肾炎常见，临床表现以无症状血尿或尿液检查异常常见。但仍有少部分患者出现肾血管纤维素样坏死及慢性化改变。提示预后不好，建议积极肾活检。     

血清IgA浓度肾组织IgA沉积量与IgA肾病关系的研究

目的探讨IgA肾病患者血清IgA浓度、肾小球IgA沉积量与肾小球病变程度的关系。方法选取66例经病理证实的IgA肾病肾活检标本,分为轻度系膜增生(A组)、中-重度系膜增生(B组)、局灶增生或增生硬化性IgA肾病(C组)3组,并以20例肾小球微小病变肾穿刺活检标本作为对照。收集所选病例血清IgA浓度的实验室资料,用免疫荧光技术配合激光共聚焦显微镜检测IgA免疫复合物在肾小球的沉积量。结果①IgA肾病患者血清IgA浓度与肾组织IgA免疫复合物沉积量无相关性(r=0.35,P>0.05)。②肾组织IgA免疫复合物沉积量与IgA肾病病变有一定关系。结论血清IgA浓度的高低可能不是IgA肾病发生的决定性因素,但肾组织沉积的IgA免疫复合物可能在肾小球细胞外基质的过量积聚、肾小球硬化过程中起重要作用。     

伴慢性扁桃体炎IgA肾病的临床病理特征和疗效分析

目的 探讨伴慢性扁桃体炎IgA肾病临床病理特征和疗效.方法 回顾性分析伴或不伴慢性扁桃体炎的两组IgA肾病患者的临床及病理资料,比较两组的临床病理特征及疗效.所有患者肾活检病理根据国际IgA肾病协作组提出的牛津分型进行分类.连续变量采用t检验或Mann-Whitney U检验,分类变量采用x2检验分析.结果 伴慢性扁桃体炎组高于不伴慢性扁桃体炎组的高血压发生率(62.5％vs 20.5％,P=0.002)、尿红细胞≥2+比例(62.5％vs 34.1％,P=0.048)、血TG[(3.3±2.2)mmol/L vs(2.0±1.3)mmol/L,P=0.038].两组病理特征、疗效差异无统计学意义(P<0.05).结论 伴慢性扁桃体IgA肾病的高血压、血尿、血脂紊乱更严重,病理特征和疗效与不伴慢性扁桃体炎相似.     

原发性肾病综合征并发急性肾损伤48例临床病理分析

目的探讨原发性肾病综合征合并急性肾损伤的临床及病理特点,提高此类并发症的防治水平。方法对我院原发性肾病综合征合并急性肾损伤患者的临床和病理改变进行回顾性分析。结果原发性肾病综合征合并急性肾损伤的临床特征表现为大量蛋白尿、高度水肿,常合并胸腹腔积液。肾脏病理类型:系膜增生性肾小球肾炎、肾小球微小病变及IgA肾病多见。其中系膜增生性肾小球肾炎22例,占46%;微小病变型10例,IgA肾病9例。所有患者均依据病理分型给予激素和(或)细胞毒药物,同时行利尿、控制感染、抗凝等综合治疗,其中5例进行血液透析治疗,肾损伤大多好转,但增生硬化型肾炎等预后较差。结论原发性肾病综合征并发急性肾损伤临床并不少见,多发生于系膜增生性肾小球肾炎、肾小球微小病变及IgA肾病,尽早明确病理诊断和去除诱因,并予相应治疗,大多患者预后良好,肾功能可恢复正常。     

伴蛋白尿IgA肾病患者病理表现与疗效关系

目的分析伴蛋白尿IgA肾病病理表现与疗效的关系。方法回顾性分析接受肾素-血管紧张素系统抑制剂和激素治疗有效和无效的两组伴蛋白尿IgA肾病患者的临床及病理资料。所有患者肾活检病理根据国际IgA肾病协作组提出的牛津分型进行分类。连续变量采用t检验或Mann-Whitney U检验,分类变量采用χ2检验分析。结果两组患者临床特征的差异无统计学意义,无效组毛细血管内细胞增殖(E1)比例高于有效组(66.7%vs 28.6%,P=0.023)。结论临床特征对判断伴蛋白尿IgA肾病疗效无提示意义,而牛津分型中毛细血管内细胞增殖(E1)可能有助于预测该类患者的疗效。     

316例肾组织活检病理资料分析

目的:分析我市成人肾活检患者各种肾脏病理构成比例及其临床表现关系。方法:对316例肾病患者肾组织病理活检以及临床资料进行回顾性分析。结果:原发性肾小球疾病是最常见的肾脏疾病,其中IgA肾病最多见;继发性肾脏疾病以狼疮性肾炎、过敏性紫癜性肾炎、乙肝相关性肾炎和肥胖相关性肾炎最常见。原发性肾病综合征以非IgA系膜增生型肾病最常见,其次为IgA肾病。结论:原发性肾小球疾病是最常见的肾脏疾病,其中以IgA肾病最常见;继发性肾脏疾病以狼疮性肾炎和过敏性紫癜性肾炎最常见;原发性肾病综合征中非IgA系膜增生型肾病最常见。     

过敏性紫癜性肾炎与IgA肾病临床及病理的对比研究

目的 对比研究过敏性紫癜性肾炎(HSPN)和IgA肾病在临床及肾脏病理改变上的异同,探讨两者的关系.方法 对经肾活检证实的40例过敏性紫癜性肾炎患者及38例IgA肾病患者进行详细的临床及病理对比分析.结果 HSPN与IgA肾病临床表现类型分布上相似,两者都以血尿伴蛋白尿居多(42.5%vs55.3%),但HSPN的肾病综合征发生率(25.0%)高于IgA肾病(7.9%),差异有统计学意义(P＜0.05).早期高血压发生率(20.0%vs21.1%)两组患者无统计学意义.肉眼血尿发生率(26.3%vs5.0%)及肾功能异常发生率(26.3%vs7.5%)IgA肾病高于HSPN(P＜0.05).HSPN肾外症状均有皮肤紫癜,25%有胃肠症状,20%有关节痛,而IgA肾病仅5.3%有腹痛.在肾脏病理改变上,IgA肾病23.7%出现球性硬化,44.7%出现肾小管萎缩,HSPN为5.0%及22.5%,但HSPN有17.5%出现内皮增生,IsA肾病患者则未见,差异均有统计学意义(P＜0.05).新月体形成及弥漫性系膜增生等病理表现二者并无明显差别(11vs12,3vs3,P＞0.05).HSPN患者中20例(50.0%)肾小球免疫沉积物中含有IgG,而IgA肾病肾小球免疫沉积物中有IgG沉积者仅为6例(15.8%),差异有统计学意义(P＜0.05).结论 过敏性紫癜性肾炎和IgA肾病有极其相似的病理特点,但在临床表现、病理变化、免疫机制上存在明显差异,支持它们是两个疾病实体.     

伴有高血压的IgA肾病临床表现、病理特点及高血压发生的影响因素分析

目的 探讨伴有高血压的IgA肾病(IgAN)的临床表现、病理特点及影响高血压发生的相关因素.方法 选取2013年1月-2015年12月收治的经肾穿刺活检术确诊为IgAN的82例.根据血压状况分为高血压组(A组)33例和非高血压组(B组)49例.分析两组一般情况、临床表现和病理资料,比较两组临床指标和病理特点.结果 A组贫血、高尿酸血症、肾功能不全发生率高于B组(P＜0.05),而水肿、血尿的发生率比较差异无统计学意义(P＞0.05).A组24 h尿蛋白定量高于B组,病理损害重于B组(P＜0.05).A组病理类型以系膜增生性肾小球肾炎为主,占60.61％.A组肾小球硬化和血管病变发生率高于B组,肾间质病变程度较B组重,新月体形成率低于B组(P＜0.05).24 h尿蛋白定量、高尿酸血症、系膜增生、肾小球硬化、肾间质病变、动脉内膜增厚及透明变性与IgAN高血压的发生呈正相关,而新月体形成与其呈负相关(P＜0.05).多因素Logistic回归分析结果显示,24 h尿蛋白定量为IgAN高血压发生的独立危险因素.结论 伴高血压的IgA肾病患者贫血、高尿酸血症、肾功能不全发生率高,24 h尿蛋白定量高,病理损害重.     

肝细胞生长因子 转化生长因子-β_1在IgA肾病肾组织的表达及意义

目的对IgA肾病肾组织进行肝细胞生长因子(HGF)、转化生长因子(TGF)-β1水平测定,探讨其与IgA肾病肾脏病理分型、Katafuchi评分及临床指标的关系。方法①76例IgA肾病患者肾脏组织被分为轻度系膜增生(A组)、中到重度系膜增生(B组)、局灶增生或增生硬化性IgA肾病(C组)3组;②采用Katafuchi的半定量标准评分,计算相应的肾小球总积分、系膜增生程度积分、球性硬化积分、血管积分;③检测患者的血压、尿蛋白定量(24h)、血清肌酐(Scr)、内生肌酐清除率(Ccr)、血清白蛋白(Alb)和脂蛋白a[Lp(a)];④免疫组织化学及反转录-聚合酶链反应(RT-PCR)方法测定患者肾组织切片中HGF、TGF-β1水平,收集数据进行统计分析。结果①随着病变的加重,各病理指标相应积分及血压、Lp(a)、尿蛋白定量(24h)、Scr逐渐增加,Ccr、Alb逐渐降低;②与A组比较,B组肾组织TGF-β1明显增多(P<0.01),C组显著降低(P<0.05);与A组比较,B、C组HGF面积显著降低(P<0.01);③肾组织HGF阳性面积与Ccr、Alb呈正相关(r=0.76、r=0.60),与肾组织TGF-β1阳性面积无相关,与血压、、Scr、Lp(a)、肾小管间质积分、肾小球总积分、系膜增生程度积分、球性硬化积分、血管积分呈负相关(r分别=-0.69、-0.75、-0.70、-0.67、-0.74、-0.69、-0.35、-0.39、-0.32,P<0.01)。结论①各临床病理指标与病理分级有相关性,提示动态监测临床病理指标对判断IgAN的预后有意义;②IGF-β1参与肾纤维化过程;随肾脏病变的加重HGF含量降低,可导致其纤维化作用减弱。     

Dihydroartemisinin inhibits the proliferation of IgAN mesangial cells through the mTOR signaling pathway

IgA nephropathy (IgAN) is an autoimmune kidney disease and is the most prevalent form of glomerular kidney disease in China and worldwide. IgA immune complex deposition accompanied by mesangial cell proliferation and mesangial matrix expansion is the most basic pathological feature of IgAN. Dihydroartemisinin (DHA), an antimalarial drug, was recently reported to be effective in treating autoimmune diseases. However, its potential therapeutic role in IgAN is relatively unstudied. The aim of this study was to investigate the pharmacological effects and the underlying mechanisms of DHA in the treatment of IgAN. In this study, renal biopsy specimens were collected for immunohistochemistry. In vitro, 25 μg/ml concentrations of aggregated IgA1 (aIgA1) was used to construct the IgAN mesangial cell model. Stimulated human mesangial cells (HMCs) were treated for 24 h with DHA (0–15 μM) and were collected for western blot analyses. Cell proliferation was assessed by Cell Counting Kit 8 (CCK8) and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. In vitro, our results showed that DHA could downregulate the mammalian target of rapamycin/ribosomal protein S6 kinase beta-1 (mTOR/S6K1) signaling pathway, promote cell autophagy, and ameliorate cell proliferation in aIgA1-induced HMCs. The results suggested that DHA may represent a novel class of mTOR inhibitor and promote an anti-proliferation effect in IgAN HMCs, which provides an alternative approach for IgAN treatment.     

Detection of immunoglobulin depositions by immunofluorescence and/or immunoperoxidase (P-AP method) in patients with IgA nephropathy

Deposition of immunoglobulins in the glomeruli by immunoperoxidase (IP) and/or immunofluorescence (IF) using unfixed materials obtained from 25 patients with IgA nephropathy (IgAN) was evaluated. The results indicated that the deposition of IgA, IgM or IgG in the glomerular capillary walls using a peroxidase anti-peroxidase (P-AP) method was more prominently detected than by using IF. The results of double staining indicated that both P-AP and IF were able to stain mesangial and capillary depositions of IgA was more widely detected by P-AP than by IF. It is concluded that the P-AP method has the advantage of indicating the deposition of immunoglobulins in glomerular capillary walls, and evaluating the histopathological significance together with IF in patients with IgAN.     

Toll-like receptor 4 is involved in a protective effect of rhein on immunoglobulin A nephropathy

Objectives:The objective was to investigate the protective effects of rhein on renal histology change and the effects of rhein on renal tissue toll-like receptor (TLR) 4, TLR9, transforming growth factor-β1 (TGF-β1) expression in immunoglobulin A nephropathy (IgAN) rats.Results:The biochemical parameters results of IgAN model rats showed that the 24-h UP excretion and ALT concentration were much higher, and TP concentration was much lower than those of the control group (P < 0.05). Granule-like or mass-like IgA depositions in the mesangial area, glomerular hypercellularity, hyperplasia of mesangial matrix, and tubulointerstitial fibrosis were found in IgAN group. Rhein-prevented and rhein-treated both improved the biochemical parameters and relieved renal pathological injury. The expressions of renal tissue TLR4, TGF-β1, but not TLR9 were significantly elevated in IgAN model rats (P < 0.05). Rhein-prevented and rhein-treated both inhibited TLR4 and TGF-β1 expressions.Conclusion:Rhein significantly improved the serum and urine biochemical parameters, and attenuated the glomerular pathological changes and tubulointerstitial fibrosis in IgAN rats. The mechanism may involve inhibition of renal TLR4 and TGF-β1 secretion.KEY WORDS: Immunoglobulin A nephropathy, rhein, toll-like receptor, transforming growth factor-β1     

缬沙坦对IgA肾病大鼠血清IgA1异常糖基化的影响

目的观察IgA肾病（IgAN）大鼠血清IgA1异常糖基化的程度及缬沙坦对其影响。方法将6sD大鼠随机分为正常对照组、IgAN组、缬沙坦组、泼尼松组,每组12只。采用口服牛血清白蛋白（BSA）和尾静脉注射BSA和葡萄球菌肠毒素（sEB）的方法建立IgAN大鼠模型,缬沙坦组给予缬沙坦30mg·kg-1·d-1,泼尼松组给予泼尼松5mg·k-1·d-1,灌胃给药。分别于1,8,12周测24h尿蛋白量;12周处死大鼠取血,ELISA法测血清IgA含量,凝集素亲和ELISA法检测血清IgA异常糖基化的程度;肾组织切片观察病理学改变。结果造模8周后IgAN组、缬沙坦组、泼尼松组大鼠尿蛋白较正常对照组显著增多,第12周时缬沙坦组及泼尼松组尿蛋白较IgAN组显著减少。IgAN组血清IgA水平较正常对照组显著升高,缬沙坦组及泼尼松组均较IgAN组显著减少。IgAN组大鼠光镜下肾系膜基质增生,系膜细胞增多,部分毛细血管攀闭塞;荧光下IgA呈团块状在系膜区沉积;缬沙坦组及泼尼松组病理较IgAN组显著改善,正常对照组未见病理改变。IgAN组IgA异常糖基化程度最重,缬沙坦组较IgAN组显著改善,泼尼松组无明显改善。结论缬沙坦能显著降低血清IgA的水平,改善血清IgA1异常糖基化程度,改善临床及病理损伤。可见改善igA1异常糖基化程度可能是缬沙坦治疗IgAN的重要机制之一。     

IgA肾病患者的肾脏病理学特征

目的分析IgA肾病的肾脏病理特点。方法回顾性分析经皮肾穿刺确诊为IgA肾病的407例患者的病理资料。结果 IgA肾病Lee氏分级以Ⅱ级、Ⅲ级为主。病理表现上,局灶节段病变占38.04%,系膜增生型占32.24%,轻微病变型占24.28%。Lee氏分级与免疫荧光沉积强度相关(Z=17.187,P<0.05)。结论 IgA肾病患者的病理表现多样。Lee分级与免疫荧光强度存在一定的相关性。     

Protection of rhein on IgA nephropathy mediated by inhibition of fibronectin expression in rats

Objective:

To investigate the protective effects of rhein on IgA nephropathy (IgAN) in the rat model.

Materials and Methods:

Twenty-eight female sprague dawley rats were divided randomly into four groups, namely control, IgAN, rhein-prevented and rhein-treated. The pathologic changes on renal tissue were observed by the H and E, staining and the amount of urinary red blood cells and 24-h urinary protein excretion were measured. The glomerular deposition of immune globulin A (IgA) was measured by immunofluorescence staining. Fibronectin (FN) and α-smooth muscle actin (α-SMA) expression on renal tissue were measured via immunohistochemistry.

Results:

The model of IgAN was established according to Bovine serum albumin-Lipopolysaccharide-Carbon tetrachloride protocol, which was evidenced by histological structural lesions of glomeruli, IgA deposition and urinary measurement. Histological examination of kidney sections from both rhein-prevented group and rhein-treated group showed that glomerular hypertrophy, mesangial expansion, excessive extracellular matrix, and renal capsule dilation were markedly ameliorated compared with IgAN group. Moreover, rhein treatment significantly reduced IgA deposition in glomerulus, the volume of urinary red blood cells and 24-h urinary protein excretion. More importantly, increased FN expression in IgAN was back to normal level in rhein-prevented and rhein-treated group, which was along with the reduction of α-SMA expression in renal tissues.

Conclusions:

These findings indicate that rhein prevents the development of glomerulosclerosis and halts the progression of IgAN via inhibition of FN and α-SMA expression.KEY WORDS: IgA nephropathy, rat, rhein     

肾组织活检359例临床病理分析

目的：探讨成人肾活检患者各种肾脏病理构成比例及其临床表现关系。方法：参照WHO肾小球疾病组织学分型方案,回顾性分析359例肾活检的临床资料。结果：患者平均年龄（29.26±14）岁。原发性肾小球疾病占首位（55.99%）,继发性肾小球疾病占44.01%。原发性肾小球疾病的病理类型中最多见者为系膜增生性肾小球肾炎（49.25%）,其次为IgA肾病（29.85%）和局灶节段性肾小球硬化（8.96%）。继发性肾小球疾病中狼疮性肾炎（34.18%）占首位,其次为紫癜性肾炎（21.52%）和乙肝相关性肾炎（17.09%）。结论：以原发性肾脏疾病最常见,其中系膜增生性肾小球肾炎是最常见的病理类型,其次为IgA肾病。继发性肾小球疾病以狼疮性肾炎、紫癜性肾炎和乙肝相关性肾炎居3位。原发性肾病综合征中非IgA系膜增生型肾病最常见。     

白藜芦醇通过抑制系膜区细胞增殖下调PDGF-B、TGF-β1表达减缓大鼠IgAN进展

目的探讨SirT1激动剂白藜芦醇(resveratrol,Res)对IgAN大鼠的治疗效果及其作用机制。方法建立IgA肾病大鼠模型,将大鼠随机分成4组:正常对照组(Control组)、IgA肾病组(IgAN组)、正常对照+Res组(Control+Res组)、IgA肾病+Res组(IgAN+Res组)。丽春红S法检测尿蛋白及自动生化分析仪检测各项生化指标;PAS和Masson染色法观察肾脏病理改变;免疫荧光观测IgA沉积情况;免疫组化法检测PDGF-B、TGF-β1的表达。结果与IgAN组相比,白藜芦醇干预组24 h尿蛋白量、尿素氮、血肌酐表达明显降低,肾小球IgA荧光沉积明显减少;IgAN组后期系膜区细胞及基质增生、肾小球体积增大均受到明显抑制;白藜芦醇还显著降低IgAN组PDGF-B、TGF-β1的高表达。结论白藜芦醇能够显著减少IgA肾病大鼠肾脏IgA免疫复合物在系膜区的沉积,并通过抑制系膜区细胞增殖下调PDGF-B及TGF-β1的表达来减轻肾小球硬化,从而起到减缓大鼠IgA肾病进展的作用。     

IgA肾病肾血管病变与临床病理之间的关系

目的：探讨IgA肾病（IgAN）肾血管病变的临床和病理学意义。方法：将177例经肾活检确诊的原发IgAN患者分为肾血管病变组及无肾血管病变组,比较两组临床指标及病理改变与血管病变之间的关系。结果：177例IgAN患者中有肾血管病变者占65．5％。与无肾血管病变组相比,肾血管病变组血压升高、尿蛋白增多、血肌酐升高、病理分级加重,肾小球补体C3沉积更明显。结论：IgAN肾血管病变与临床和病理变化显著相关,可以作为判断预后的一项重要病理指标。