Cagnoli L
G Ital Nefrol. 2003 Sep-Oct;20 Suppl 24:S3-47.
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.
这一系列关于肾小球肾炎(GN)管理的文章由一组专家以循证医学格式编写,符合已发表数据的同行评审要求。每位作者被要求针对其指定的组织学类型查阅文献,重点关注治疗方法,且限于成人研究。微小病变肾病和局灶节段性肾小球硬化症未设定年龄限制,因为这些肾小球疾病在儿童中发病率较高。每位作者根据这些综述研究中提供的证据量,对每种类型肾小球疾病的具体治疗建议进行分级。前两篇文章重点关注肾活检的适应证和技术。随后的每篇文章都聚焦并描述了支持IgA肾病(Ig - GN)、微小病变肾病(MCN)、局灶节段性肾小球硬化症(FSGS)、膜性肾小球肾炎(MGN)、狼疮性肾炎、抗中性粒细胞胞浆抗体相关性血管炎、丙型肝炎病毒相关性冷球蛋白血症以及副蛋白血症性疾病肾损害治疗建议的最高级别证据。关于IgA肾病的文章强调在确定治疗方案之前仔细评估临床和组织学发现的重要性。详细讨论了近期对类固醇和许多免疫抑制剂重新燃起的兴趣。还提供了与患者年龄相关的建议。MCN和FSGS合并讨论,因为这两种类型有相似的循证医学建议。事实上,对于这两种疾病,儿童的初始治疗方法应为使用泼尼松或泼尼松龙治疗四至六周。成人的治疗反应比儿童慢,但成人复发较少且缓解期更长。还讨论了复发、频繁复发疾病和真正类固醇抵抗性疾病的治疗以及新型免疫抑制剂的作用。膜性肾病是成人肾病综合征的常见病因,其中三分之一的患者会发展为终末期肾病。然而,这种类型的治疗方法仍存在争议。基于对文献的广泛批判性综述,提出以下建议:(a)无肾病综合征时无需治疗;(b)重度蛋白尿患者应接受为期6个月的治疗,静脉注射甲泼尼龙(MP)冲击治疗连续三天,随后口服MP(0.4mg/kg/天)(第1、3、5个月)以及苯丁酸氮芥或环磷酰胺(第2、4、6个月);(c)老年患者应降低苯丁酸氮芥或环磷酰胺的剂量;(d)环孢素是二线治疗药物。狼疮性肾炎的治疗取决于组织学分类。I类和IIA类通常无需特殊治疗。IIb类、有蛋白尿且有活动性全身疾病的患者需口服类固醇治疗。III类和IV类患者的首选治疗是类固醇和硫唑嘌呤,但环孢素也可作为有效的替代疗法。存在严重急性肾损害时,环磷酰胺比硫唑嘌呤更有效。抗中性粒细胞胞浆抗体相关性血管炎的治疗主要取决于临床表现,口服泼尼松 + 口服或静脉注射环磷酰胺通常有效。在最严重的病例中,MP冲击治疗联合环磷酰胺可能更有效。对无反应的患者可能需要进行血浆置换。维持治疗期间硫唑嘌呤应替代环磷酰胺。在丙型肝炎病毒相关性混合冷球蛋白血症中,治疗也取决于肾损害的严重程度。慢性丙型肝炎感染的治疗单独使用α干扰素,或最好与利巴韦林联合使用。积极的治疗,包括静脉注射MP、血浆置换和环磷酰胺,主要用于患有急性重症疾病的患者,如进行性肾衰竭、需要截肢的远端坏死或晚期神经病变。非对照研究表明,这种治疗方案可改善肾功能。肾损害是副蛋白血症性疾病(包括多发性骨髓瘤、华氏巨球蛋白血症和单克隆丙种球蛋白病)中的常见问题。在此情况下最常见的肾脏疾病是管型肾病、原发性淀粉样变性管型肾病、原发性淀粉样变性以及与单克隆免疫球蛋白轻链过度产生相关的轻链沉积病。治疗方法因肾功能障碍的病因而异。淀粉样变性或轻链沉积病患者通常接受化疗,但骨髓瘤肾病最有效的治疗方法是通过尽量减少促进轻链滤过及随后肾小管内管型形成阻塞的危险因素来预防。几乎所有患者都需要进行化疗或干细胞或骨髓移植以减少滤过的轻链负荷、防止容量耗竭并保持高液体摄入量以降低肾小管腔内轻链浓度。