Salvadori Maurizio, Rosso Giuseppina
Maurizio Salvadori, Department of Renal Transplantation, Careggi University Hospital, 50139 Florence, Italy.
World J Nephrol. 2016 Jul 6;5(4):308-20. doi: 10.5527/wjn.v5.i4.308.
This review revises the reclassification of the membranoproliferative glomerulonephritis (MPGN) after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and pathogenesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized: The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecific treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in finding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies.
本综述对膜增生性肾小球肾炎（MPGN）的重新分类进行了修订，该修订是在2015年的共识会议之后进行的，此次会议根据病因和发病机制而非组织形态学方面对所有肾小球肾炎进行了重新分类。重新分类后，目前已确认两种类型的MPGN：免疫复合物介导的MPGN和补体介导的MPGN。在本综述中，对后一种类型进行了更广泛的描述，这要么是因为其中一些实体是全新的，要么是因为对补体级联反应的认识提高使得新的诊断和治疗方法成为可能。总体而言，补体介导的MPGN与后天或遗传原因有关。循环自身抗体的存在是主要的后天原因。全基因组关联研究和家族研究使得能够识别不同类型的基因突变是补体失调的原因。补体级联反应是一个复杂的现象，应区分激活因子和调节因子。已经描述了导致激活因子或调节因子异常的基因突变。补体介导的MPGN的诊断需要对所有这些不同的补体因子进行全面研究。因此，新的治疗方法正在出现。事实上，除了旨在阻断自身抗体产生的非特异性治疗和免疫抑制外，补体激活的特异性抑制相对较新，可能通过阻断C5转化酶或C3转化酶起作用。作用于C3转化酶的药物仍处于临床开发的不同阶段，可能代表未来的药物。总体而言，作者认为寻找新型药物的主要问题之一是该疾病的罕见性以及随之而来的市场关注度低和缺乏大型国际合作研究。
