IgG4在特发性膜性肾病中的研究进展

目前认为IMN是由于IgG与肾小球足细胞基底膜侧的固有抗原结合进一步激活补体而致病,其中沉积的IgG亚类以IgG4为主.IgG4沉积如何致病尚未澄清,本文就这一领域的研究进展作一综述.     

足细胞与膜性肾病

膜性肾病以肾小球基底膜上皮细胞下弥漫性的免疫复合物沉积伴基底膜弥漫增厚为特点，对本病发病机制的研究主要是基于动物实验，即对海曼肾炎动物模型这种类似人类膜性肾病的动物模型的研究。在这种模型中，免疫复合物在基底膜上皮细胞下形成，导致补体途径活化进而形成C5b-9膜攻击复合物，最终导致补体介导的足细胞损伤。     

抗足细胞抗体在原发性膜性肾病发病机制中的作用

目的 研究抗足细胞抗体在原发性膜性肾病(MN)发病机制中的作用.方法 制备人肾组织冰冻切片36张,随机分为A、B、C3组(每组12张),分别滴加原发性MN患者血清、IgA肾病患者血清原液以及生理盐水(血清为原液,未稀释),荧光显微镜观察各组变化.雄性新西兰大耳白兔21只,随机分为D、E、F3组(每组7只),分别注射MN患者血清、IgA肾病患者血清以及生理盐水,第2、4、6、8周观察各组白兔24 h尿蛋白量、血清白蛋白、血肌酐.第8周末处死动物,通过光镜、电镜、免疫荧光观察兔的肾脏病理变化.结果 免疫荧光结果显示,A组IgG呈细颗粒状沿肾小球足细胞沉积,其余两组均阴性.与E组和F组相比,D组白兔注射膜性肾病血清后,24h尿蛋白量显著增高(P＜0.01),血清白蛋白显著降低(P＜0.O1);第8周免疫荧光结果显示IgG呈细颗粒状沿肾小球毛细血管壁沉积;光镜显示肾小球基底膜增厚;电镜显示足突融合,上皮下可见电子致密物沉积.E组和F组未见明显病变.结论 原发性MN患者血液中存在抗足细胞抗体,是原发性MN的主要病因.     

膜性肾病的进展

对于膜性肾病患者,我们首先要根据不同的危险度给予对应治疗[11,31].尿蛋白<4g/24h,肾功能正常患者,使用ACEI±ARB,限制蛋白饮食,控制血压≤125/75mmHg,并密切监视尿蛋白和肾功能.尿蛋白4～8g/24h肾功能正常患者,除上述处理外,应密切观察6个月,病情无好转者应接受细胞毒药物治疗,如果无效可选择CsA治疗.尿蛋白>8g/24h或肾功能不全患者,应立即接受使用ACEI±ARB,限制蛋白饮食,控制血压≤125/75mmHg,观察时间≤6月,可选择CsA治疗.如果无效,可使用细胞毒加激素治疗.当一种治疗出现副作用时,可以使用CsA、FK506或MMF等替代.对于肾功能不全(Scr>354μmol/L)或肾活检示Ⅳ期、广泛间质纤维化的患者,ACEI类药物和控制血压在125/75 mm Hg仍是首选的治疗.对于持续存在肾综的患者,还应注意高脂血症、高凝倾向及免疫治疗带来副作用.     

膜性肾病的发病机理

膜性肾病是一种较为难治的常见的肾小球疾病。近年研究表明 ,膜性肾病的发病为免疫机制所介导 :主要致病抗原成分为megalin 受体相关蛋白复合体 ;肾小球上皮细胞受损可激活特殊的信号传导途径 ;细胞免疫部分参与发病 ;MHC可能与原发性膜性肾病有关。     

膜性肾病的免疫抑制治疗

特发性膜性肾病（IMN）本身不是一个均一性的疾病，在临床表现、发展经过及预后等方面不同患者差异颇大，治疗亦有其特殊性，应重视基础治疗，长期坚持，分阶段用药，因人而异，强调个体化治疗方案，应用免疫抑制剂治疗前应权衡利弊，充分考虑疗效／风险之比，减少副作用与并发症，避免过分追求尿蛋白的阴转而长期过度使用糖皮质激素和免疫抑制剂的倾向。     

特发性膜性肾病的治疗进展

目前对于特发性膜性肾病(IMN)虽无公认的治疗方法，但近年来在免疫抑制疗法和非免疫抑制疗法上均有较大的进展，也出现了众多的生化制剂，在并发症的治疗上也有较大突破。     

原发性膜性肾病合并IgA肾病两例报告并文献复习

目的 探讨原发性膜性肾病合并IgA肾病的临床表现以及病理特点,并指导临床治疗.方法 分析本院经过临床以及肾脏病理(包括光镜、免疫荧光和电镜)确诊的2例原发性膜性肾病合并IgA肾病患者的临床和病理资料,并进行文献复习.结果 两例患者均为青壮年男性,年龄分别为44岁和38岁,血压及肾功能均正常.例1表现为肾病综合征伴镜下血尿;例2表现为无症状性蛋白尿.两例患者临床上均除外继发性肾脏病,根据蛋白尿程度选用不同的治疗方案,效果良好.结论 原发性膜性肾病合并IgA肾病发病率较低,临床表现无特异性,兼具有膜性肾病和IgA肾病的病理特点.临床表现更似于膜性肾病,治疗方面则需要进行个体化的治疗.     

特发性膜性肾病发病机制研究进展

特发性膜性肾病(IMN)是成人肾病综合征最常见的类型之一,也是终末期肾病的主要病因之一。近年来,IMN发病率逐渐升高且趋向年轻化,因此全面认识IMN的发病机制至关重要。现对IMN发病机制研究进展作一综述,以期有助于临床上IMN的诊断及治疗。     

Preeclamptic nephropathy associated with membranous nephropathy

We report a patient who had nephropathy of toxemia of pregnancy associated with membranous glomerulonephritis, which deteriorated 3 months after delivery. Electron microscopy revealed electron-dense deposits on the subepithelial surface of the glomerular basement membrane and finely granular/fibrillar materials in the subendothelial space. As a result of treatment with prednisolone and anticoagulants, marked alleviation of both proteinuria and edema was achieved. We therefore consider that the change from subclinical to clinical membranous nephropathy could be attributed to pregnancy. Received: February 22, 2001 / Accepted: July 12, 2001     

Changes of autophagosomes of podocytes in idiopathic membranous nephropathy and its clinical significance

Objective To observe the quantity change of autophagosomes in podocytes and expressions of autophagy-related gene Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3) in different pathological stages of idiopathic membranous nephropathy (IMN), and to explore how autophagy is related to podocyte injury, the occurrence of proteinuria and the disease progression in IMN. Methods Clinical data of 26 patients who were diagnosed as IMN (14 IMN stage 1 and 12 IMN stage 2) admitted to Zhejiang Provincial people's Hospital from January 2013 to December 2014 were retrospectively analyzed. Normal renal tissue from 15 cases of kidney neoplasms with nephrectomy was collected as control. The changes of kidney tissue pathology were detected after PAS and PASM staining by light microscope. The autophagosomes of podocyte were detected by transmission electron microscopy. Expressions of Beclin-1 and LC3 protein were detected by immunohistochemistry. Expressions of LC3 and synaptopodin were detected by immunofluorescence. The correlation of autophagosomes and clinical pathologic factors in IMN patiens was analyzed. Results There were fewer autophagosomes of podocytes and lower expression of Beclin-1 and LC3 protein in IMN group than those in control group (P=0.034, P=0.011, P=0.013, respectively). Moreover, these effects were more obvious with the development of IMN. Compared with those in control group, autophagosomes, Beclin-1 and LC3 protien were reduced in IMN stage 2 group (P=0.009, P=0.030, P=0.015); the number of autophagosomes and the expressions of LC3 and Beclin-1 were decreased in IMN stage 1 group as well, however statistically insignificant (P=0.352, P=0.087, P=0.128); Comparisons between IMN stage 2 patients and IMN stage 1 patients shown significant difference in the number of autophagosomes (P=0.030), but no significant difference in expressions of Beclin-1 and LC3 (P=0.355, P=0.181). Autophagosomes number was not correlated with serum creatinine, serum urea nitrogen, 24-hour urinary protein and eGFR (all P＞0.05). The expressions of synaptopodin and LC3 protein were lower in IMN group than those in control group. Conclusion Autophagy may contribute to podocyte injury and the production of protein urine in IMN, and may be closely related to the progression of disease.     

Gouty kidney associated with membranous nephropathy: participation of renal tubular epithelial antigen

Histological studies were performed on 3 patients with gout and proteinuria measured at 1.0 g a day or more. Light microscopy revealed diffuse thickening of the glomerular capillary walls accompanied by spike formation and bubble-like appearance as well as tophaceous granuloma in the interstitium, tubular atrophy and benign nephrosclerosis. Immunofluorescence technique showed fine granular deposits of IgG and C3 along the glomerular capillary walls together with the renal tubular epithelial antigen (RTE) in 1 patient. Subepithelial dense deposits were also observed by electron microscopy. These findings suggest that the association of membranous nephropathy should be considered in patients with gout having moderate to severe proteinuria and that RTE may be involved in the pathogenesis of subepithelial deposits in gouty membranous nephropathy.     

Secondary polycythemia associated with membranous nephropathy

A 61-year-old male patient had secondary polycythemia associated with idiopathic nephrotic syndrome. Renal biopsy revealed membranous nephropathy. Polycythemia did not change in spite of partial remission of proteinuria. Serum erythropoietin determined by an enzyme-linked immunosorbent assay was 7.2 mU/ml. His serum erythropoietin maintained at a constant level during polycythemia was higher than it was before the appearance of renal ischemia, so he was kept in a polycythemic state. Whether decreasing proteinuria can improve renal ischemia requires future study. We must observe the patient for the occurrence of thromboembolism. Renal ischemia possibly induced by nephrotic syndrome is likely to cause secondary polycythemia.     

Case of membranous nephropathy associated with argyria

We experienced a case of membranous nephropathy associated with argyria. The patient was a 78-year-old woman who had noticed blue skin of the face and azure lunulae for 8 years. She was admitted to our hospital for edema and proteinuria. She was diagnosed as membranous nephropathy by needle renal biopsy, and treated with prednisolone. Her proteinuria disappeared after 63 days. We investigated the blue skin of her face and azure lunulae. Skin biopsy was performed and black granules deposited in the upper layer of the corium were observed. The granules were identified with silver by EDS (energy-dispersive X-ray spectroscopy) analysis. Membranous nephropathy associated with gold or mercury has been reported, but association with silver has not been reported. We considered that this is a rare case of membranous nephropathy associated with silver.     

Secondary polycythemia associated with idiopathic membranous nephropathy

A 58-year-old male patient had secondary polycythemia associated with idiopathic nephrotic syndrome. The renal biopsy revealed membranous nephropathy, and the bone marrow biopsy disclosed hypercellular marrow with mild panhyperplasia. The concentration of serum erythropoietin was 8.5 mU/ml. The erythrocytosis was characterized by an increased red cell volume (40.2 ml/kg) and normal arterial oxygen saturation. There were no associated lesions that could induce secondary polycythemia, except the biopsy-proven membranous nephropathy. He was treated with prednisolone and cyclophosphamide, and the nephrotic syndrome was partially remitted after 6 weeks. With partial remission of nephrotic syndrome, the erythrocytosis was resolved. This case illustrates the rarely reported association of the nephrotic syndrome and erythrocytosis, and the resolution of erythrocytosis with improvement of nephrotic syndrome.