Bobkova I N, Kamyshova E S
Sechenov First Moscow State Medical University (Sechenov University).
Ter Arkh. 2020 Jul 9;92(6):99-104. doi: 10.26442/00403660.2020.06.000676.
Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Since the moment of animal model creation and the recognition of podocytes damage as a key mechanism of MN development, the identification of antigens, first of all the phospholipase A2 receptor (PLA2R), and the development of methods of PLA2R autoantibodies detection and its monitoring opened a new era in the idiopathic MN (iMN) diagnosis, treatment and prognosis evaluation. MN continues to be actively studied in the new millennium, since a number of aspects of its pathogenesis still need to be clarified, and there is still no clear opinion on the iMN treatment optimal approach. Comprehensive clinical and serological assessment of patients with iMN can be the key to individual choice of treatment protocols. In patients with aPLA2R-positive iMN, the predictor of disease remission is the aPLA2R titer decrease or aPLA2R disappearance in the blood serum, and disease relapse is associated with the aPLA2R appearance ore increase of aPLA2R titer in the circulation. Studies which were conducted by today (GEMRITUX, MENTOR, STARMEN, NICE, etc.) confirmed the acceptable safety profile and effectiveness of iMN therapy by anti-CD20 monoclonal antibodies (rituximab): more than half of of iMN patients had remission of nephrotic syndrome or proteinuria decrease, remissions in anti-CD20 monoclonal antibodies treated patients were longer compared to traditional therapy. The obtained data allows us to consider rituximab and anti-CD20 antibody therapy of a new generation not only as an alternative to the more toxic treatment with cyclophosphane and calcineurin inhibitors, but as an independent promising direction of therapy for patients with IMN, which completely changes the paradigm of treatment of this glomerulopathy.
膜性肾病(MN)是成人肾病综合征最常见的病因。自从动物模型建立以及认识到足细胞损伤是MN发病的关键机制以来,抗原的鉴定,首先是磷脂酶A2受体(PLA2R)的鉴定,以及PLA2R自身抗体检测方法及其监测的发展,开启了特发性MN(iMN)诊断、治疗和预后评估的新时代。在新千年中,MN仍在积极研究,因为其发病机制的许多方面仍需阐明,并且对于iMN的最佳治疗方法仍没有明确的观点。对iMN患者进行全面的临床和血清学评估可能是个体化选择治疗方案的关键。在aPLA2R阳性的iMN患者中,疾病缓解的预测指标是血清中aPLA2R滴度降低或aPLA2R消失,而疾病复发与循环中aPLA2R出现或aPLA2R滴度升高有关。目前进行的研究(GEMRITUX、MENTOR、STARMEN、NICE等)证实了抗CD20单克隆抗体(利妥昔单抗)治疗iMN的安全性和有效性是可接受的:超过一半的iMN患者肾病综合征缓解或蛋白尿减少,与传统治疗相比,接受抗CD20单克隆抗体治疗的患者缓解期更长。所获得的数据使我们不仅可以将利妥昔单抗和新一代抗CD20抗体治疗视为环磷酰胺和钙调神经磷酸酶抑制剂等毒性更大治疗的替代方法,而且可以将其视为iMN患者有前景的独立治疗方向,这完全改变了这种肾小球病的治疗模式。