关于肾小球肾炎(GN)管理的这一系列文章是由一组专家以循证格式编写的,与已发表数据的同行评审一致。每位作者都被要求审查其指定的组织学类型的文献,强调治疗,仅限于成人研究。年龄限制不考虑微小病变和局灶性节段肾小球硬化,因为这些肾小球疾病在儿童中的患病率很高。每位作者根据这些综述研究中提供的证据数量,对每种类型的肾小球疾病的特定治疗建议进行分级。前两篇文章集中于肾脏活检的适应症和技术。随后的每篇文章都重点介绍并描述了支持IgA肾病(Ig-GN)治疗建议的最高证据。微小病变肾病(MCN)和局灶节段肾小球硬化(FSGS),膜性肾小球肾炎(MGN),狼疮性肾炎,ANCA相关性血管炎,HCV相关冷球蛋白血症和副蛋白血症的肾脏受累。有关IgA肾病的文章强调了在进行治疗之前仔细评估临床和组织学发现的重要性。最近,对类固醇和许多免疫抑制剂的新兴趣进行了详细讨论。还提供了与患者年龄相关的建议。MCN和FSGS被一起处理,因为这些表格具有类似的循证建议。对于这两种疾病,事实上,儿童的初始治疗方法应该是泼尼松或泼尼松龙,持续4~6周。成人的治疗反应比儿童慢,但成年人经历更少的复发和更长时间的缓解。还有关于治疗复发的讨论,常见的复发性疾病和真正的类固醇抗性疾病以及新的免疫抑制剂的作用。膜性肾病是成人肾病综合征的常见原因,三分之一的病人,导致终末期肾病.然而,这种形式的处理还在讨论中。基于对文献的广泛批判性回顾,提出了以下建议:(a)在没有肾病综合征的情况下不进行治疗;(b)重度蛋白尿患者应连续三天接受静脉注射甲基强的松龙(MP)脉冲治疗6个月,然后口服MP(0.4mg/kg/天)(1、3、5个月)和苯丁酸氮芥或环磷酰胺(2、4、6个月);(2、4、6个月)患者应降低环磷酰胺的狼疮性肾炎的治疗取决于组织学类型。I类和IIA类通常不需要特殊治疗。IIb类患者需要口服类固醇,蛋白尿和活动性全身性疾病。类固醇和硫唑嘌呤是III和IV类患者的首选治疗方法,但环孢素是一种有效的替代疗法.当存在严重的急性肾脏受累时,环磷酰胺比硫唑嘌呤更有效。ANCA相关性血管炎的治疗主要取决于临床表现,口服泼尼松+口服或静脉内环磷酰胺通常是有效的。在最严重的情况下,MP冲击治疗与环磷酰胺联合可能更有效.在无反应的患者中,血浆置换可能是合理的。硫唑嘌呤在维持治疗期间应替代环磷酰胺。在HCV相关的混合型冷球蛋白血症中,治疗还取决于肾脏受累的严重程度。慢性HCV感染的治疗涉及单独的α干扰素或优选地与利巴韦林组合。积极的治疗,包括静脉注射MP,血浆置换和环磷酰胺主要用于急性重症患者,表现为进行性肾衰竭,远端坏死需要截肢,或者是晚期神经病.非对照研究表明,该方案可以改善肾功能。肾脏受累是包括多发性骨髓瘤在内的副蛋白血症的常见问题。瓦尔登特罗姆巨球蛋白血症和单克隆丙种球蛋白病。这种情况下最常见的肾脏疾病是铸型肾病,原发性淀粉样变性铸型肾病,原发性淀粉样变性,以及与单克隆免疫球蛋白轻链过度生产有关的轻链沉积病。治疗方法因肾功能不全的原因而异。患有淀粉样变性或轻链沉积疾病的患者通常接受化疗,但对骨髓瘤肾脏最有效的治疗方法是通过减少促进轻链过滤和随后在小管内形成管型阻塞的危险因素来预防。化疗或干细胞或骨髓移植以减少过滤的轻链负荷,在几乎所有的患者中都表明防止体积消耗和维持高的液体摄入以降低管腔内的轻链浓度。
This series of articles on the management of glomerulonephritis (GN) has been prepared by a team of experts in the evidence-based format consistent with peer review of published data. Each author was asked to review the literature for his assigned histological type, with emphasis on therapy and limited to adult studies. The age limit was not considered for minimal change disease and focal segmental glomerulosclerosis, because of the high prevalence of these glomerulopathies in children. The particular treatment recommendations for each type of glomerular disease were graded by each author according to the amount of evidence provided in these reviewed studies. The first two articles concentrate on indications and techniques for kidney biopsy. Each subsequent article focuses on and describes the highest level of evidence supporting the recommendation for therapy in IgA nephropathy (Ig-GN), minimal change nephropathy (MCN) and focal segmental glomerulosclerosis (FSGS), membranous glomerulonephritis (MGN), lupus nephritis, ANCA-associated vasculitis, HCV-associated cryoglobulinaemia and renal involvement in paraproteinemic disorders. The article on IgA nephropathy emphasises the importance of carefully evaluating both clinical and histologic findings before settling on the treatment. The recent, renewed interest in steroids and many immunosuppressive agents is discussed in detail. Recommendations related to the patient\'s age are also provided. MCN and FSGS are treated together because these forms share similar evidence-based recommendations. For both of these diseases, in fact, the initial treatment approach in children should be prednisone or prednisolone for four to six weeks. The therapeutic response in adults is slower than in children, but adults experience fewer relapses and a more prolonged remission. There is also a discussion on treatment of relapse, frequent relapsing disease and true steroid-resistant disease as well as the role of new immunosuppressive agents. Membranous nephropathy is a frequent cause of nephrotic syndrome in adults and, in one third of these patients, leads to end-stage renal disease. However, the treatment of this form is as yet a matter of discussion. Based on extensive critical review of the literature, the following recommendations are put forward: (a) no treatment in the absence of nephrotic syndrome; (b) patients with heavy proteinuria should receive a 6-month treatment with i.v. methylprednisolone (MP) pulse therapy for three consecutive days followed by oral MP (0.4 mg/kg/day) (months 1, 3, 5) and chlorambucil or cyclophosphamide (months 2, 4, 6); (c) the dosage of chlorambucil or cyclophosphamide should be lowered in older patients; (d) cyclosporine is a second-choice treatment. The treatment of lupus nephritis depends on the histologic class. No specific treatment is usually necessary for class I and IIA. Oral steroids are indicated in patients with class IIb, proteinuria and active systemic disease. Steroids and azathioprine are the treatment of choice for patients with class III and IV, but cyclosporine can be an effective alternative therapy. Cyclophosphamide is more effective than azathioprine when severe acute renal involvement is present. The treatment of ANCA-associated vasculitis depends mainly on clinical presentation, oral prednisone + oral or i.v. cyclophosphamide are generally effective. In the most severe cases, the association of MP pulse therapy with cyclophosphamide is probably more effective. Plasma exchange is probably justified in unresponsive patients. Azathioprine should replace cyclophosphamide during the maintenance therapy. In HCV-associated mixed cryoglobulinemia the treatment also depends on the severity of renal involvement. The treatment for chronic HCV infection involves alpha interferon alone or preferably in combination with ribavirin. Aggressive therapy, including i.v. MP, plasmapheresis and cyclophosphamide is primarily reserved for patients with acute severe disease, as manifested by progressive renal failure, distal necroses requiring amputation, or advanced neuropathy. Uncontrolled studies suggest that this regimen can improve renal function. Renal involvement is a common problem in paraproteinemic disorders that include multiple myeloma, Waldentrom\'s macroglobulinaemia and monoclonal gammopathy. The most common renal diseases in this setting are cast nephropathy, primary amyloidosis cast nephropathy, primary amyloidosis, and light chain deposition disease that are related to the overproduction of monoclonal immunoglobulin light chains. The approach to therapy varies with the cause of the renal dysfunction. Patients with amyloidosis or light-chain deposition disease are generally treated with chemotherapy, but the most effective therapy for myeloma kidney is prevention by minimising the risk factors that promote light chain filtration and subsequent obstruction by cast formation within the tubules. Chemotherapy or stem cell or bone marrow transplantation to decrease filtered light chain load, prevent volume depletion and maintain high fluid intake to reduce light chain concentration within the tubular lumen are indicated in almost all the patients.