Caravaca-Fontán Fernando, Yandian Federico, Fervenza Fernando C
Department of Nephrology, Instituto de Investigación Hospital "12 de Octubre" (imas12), Madrid, Spain.
Department of Nephrology, Hospital de Clínicas "Dr Manuel Quintela", Montevideo, Uruguay.
Clin Kidney J. 2023 Mar 10;16(8):1228-1238. doi: 10.1093/ckj/sfad041. eCollection 2023 Aug.
Among all glomerular diseases, membranous nephropathy (MN) is perhaps the one in which major progress has been made in recent decades, in both the understanding of the pathogenesis and treatment. Despite the overall significant response rates to these therapies-particularly rituximab and cyclical regimen based on corticosteroids and cyclophosphamide-cumulative experience over the years has shown, however, that 20%-30% of cases may confront resistant disease. Thus, these unmet challenges in the treatment of resistant forms of MN require newer approaches. Several emerging new agents-developed primarily for the treatment of hematological malignancies or rheumatoid diseases-are currently being evaluated in MN. Herein we conducted a narrative review on future therapeutic strategies in the disease. Among the different novel therapies, newer anti-CD20 agents (e.g. obinutuzumab), anti-CD38 (e.g. daratumumab, felzartamab), immunoadsorption or anti-complement therapies (e.g. iptacopan) have gained special attention. In addition, several technologies and innovations developed primarily for cancer (e.g. chimeric antigen receptor T-cell therapy, sweeping antibodies) seem particularly promising. In summary, the future therapeutic landscape in MN seems encouraging and will definitely move the management of this disease towards a more precision-based approach.
在所有肾小球疾病中,膜性肾病(MN)可能是近几十年来在发病机制理解和治疗方面取得重大进展的疾病之一。尽管这些疗法(特别是利妥昔单抗以及基于皮质类固醇和环磷酰胺的周期性方案)总体上有显著的缓解率,但多年来的累积经验表明,20% - 30%的病例可能面临难治性疾病。因此,MN难治形式治疗中这些未满足的挑战需要更新的方法。几种主要为治疗血液系统恶性肿瘤或类风湿疾病而开发的新型药物目前正在MN中进行评估。在此,我们对该疾病未来的治疗策略进行了叙述性综述。在不同的新型疗法中,新型抗CD20药物(如奥妥珠单抗)、抗CD38药物(如达雷妥尤单抗、费尔扎妥单抗)、免疫吸附或抗补体疗法(如iptacopan)受到了特别关注。此外,几种主要为癌症开发的技术和创新(如嵌合抗原受体T细胞疗法、清扫抗体)似乎特别有前景。总之,MN未来的治疗前景令人鼓舞,肯定会使该疾病的管理朝着更精准的方法发展。