Instituto de Investigación Hospital 12 de octubre (i+12), Madrid, Spain,
Department of Medicine, Universidad Complutense de Madrid, Madrid, Spain,
Nephron. 2020;144(6):272-280. doi: 10.1159/000507254. Epub 2020 May 5.
C3 glomerulopathy (C3G) is a clinicopathologic entity secondary to dysregulation of the alternative complement pathway in plasma and the glomerular microenvironment. The current consensus definition of C3G relies on immunofluorescence staining criteria. However, due to its high clinical variability, these criteria may not be accurate enough in some clinical scenarios. Thus, a new pathogenic classification based on a cluster analysis of clinical, histologic, and genetic data has recently been proposed, which could also help identify patients at higher risk of progression. Several pathogenic abnormalities in complement genes have been described, and the role of autoantibodies in the disease is increasingly recognized, but still the genotype-phenotype correlations in C3G are poorly understood. C3G may be diagnosed in both children and adults. The spectrum of clinical manifestations is wide, although one of the most common clinical presentations is proteinuria with relatively preserved kidney function. In order to standardize the evaluation of kidney biopsies from these patients, a histopathologic index was recently proposed, including both parameters of activity and chronicity. However, this index has not yet been validated in independent cohorts. Currently, no targeted therapies are available in clinical settings for the treatment of C3G, although several new molecules are under investigation. Treatment with corticosteroids plus mycophenolate mofetil has been shown to be associated with improved renal outcomes, as compared to other immunosuppressive regimens. Yet, the main determinants of treatment response with this regimen and the influence of the underlying pathogenic drivers have not been extensively studied. The therapeutic response to eculizumab, an anti-C5 monoclonal antibody, has been shown to be highly heterogeneous. Thus, its current clinical indication in C3G is restricted to rapidly progressive forms of the disease. To summarize, in recent years, several important advances have taken place in the understanding of C3G, but still further studies are warranted to elucidate the best therapeutic strategies that could improve prognosis of this entity.
补体 3 肾小球病（C3G）是一种由于血浆中替代补体途径失调以及肾小球微环境异常导致的临床病理实体。目前，C3G 的共识定义依赖于免疫荧光染色标准。然而，由于其临床表现高度多样化，这些标准在某些临床情况下可能不够准确。因此，最近提出了一种基于临床、组织学和遗传数据聚类分析的新的致病分类方法，这也有助于识别进展风险较高的患者。已经描述了几种补体基因的致病性异常，并且自身抗体在疾病中的作用也越来越被认识，但 C3G 的基因型-表型相关性仍知之甚少。C3G 可发生在儿童和成人中。临床表现谱广泛，尽管最常见的临床表现之一是蛋白尿，且肾功能相对保留。为了规范这些患者的肾活检评估，最近提出了一种组织病理学指数，包括活性和慢性参数。然而，该指数尚未在独立队列中得到验证。目前，尚无针对 C3G 的靶向治疗方法可用于临床，尽管有几种新的分子正在研究中。与其他免疫抑制方案相比，糖皮质激素加霉酚酸酯治疗与改善肾脏结局相关。然而，这种方案的治疗反应的主要决定因素以及潜在致病驱动因素的影响尚未得到广泛研究。抗 C5 单克隆抗体依库珠单抗的治疗反应表现出高度异质性。因此，其目前在 C3G 中的临床适应证仅限于疾病的快速进展形式。总之，近年来，在理解 C3G 方面取得了一些重要进展，但仍需要进一步研究以阐明改善该实体预后的最佳治疗策略。
