Almanac of Clinical MedicineAlmanac of Clinical MedicineАльманах клинической медицины2072-05052587-9294Moscow Regional Research and Clinical Institute (MONIKI)64410.18786/2072-0505-2017-45-7-553-564REVIEW ARTICLEОБЗОРEvolution in the understanding of idiopathic membranous nephropathy pathogenesis: from experimental models to the clinicЭволюция в понимании патогенеза идиопатической мембранозной нефропатии: от экспериментальных моделей к клиникеBobkovaI. N.БобковаИ. Н.
Russian Federation

MD, PhD, Professor, Chair of Internal Medicine and Occupational Medicine, Faculty of Preventive Medicine

11а–23 Gagarina ul., Krasnoznamensk, Moscow Region, Moscow, 143090

Tel.: +7 (917) 559 71 43

8/2 Trubetskaya ul., 119991

д-р мед. наук, профессор

кафедра внутренних, профессиональных болезней и пульмонологии

медико-профилактический факультет

143090, Московская обл., г. Краснознаменск, ул. Гагарина, 11а–23

Тел.: +7 (917) 559 71 43

119991, г. Москва, ул. Трубецкая, 8/2

irbo.mma@mail.ruКаkhsuruevaP. A.КахсуруеваП. А.
Russian Federation

MD, Postgraduate Student, Chair of Internal Medicine and Occupational Medicine, Faculty of Preventive Medicine

8/2 Trubetskaya ul., Moscow, 119991

аспирант

кафедра внутренних, профессиональных болезней и пульмонологии

медико-профилактический факультет 

119991, г. Москва, ул. Трубецкая, 8/2

StavrovskayaE. V.СтавровскаяЕ. В.
Russian Federation

MD, PhD, Associate Professor, Chair of Internal Medicine and Occupational Medicine, Faculty of Preventive Medicine

8/2 Trubetskaya ul., Moscow, 119991

канд. мед. наук, доцент

кафедра внутренних, профессиональных болезней и пульмонологии

медико-профилактический факультет 

119991, г. Москва, ул. Трубецкая, 8/2

FilatovaE. E.ФилатоваЕ. Е.
Russian Federation

Student

8/2 Trubetskaya ul., Moscow, 119991

студентка

119991, г. Москва, ул. Трубецкая, 8/2

I.M. Sechenov First Moscow State Medical UniversityФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Минздрава России151120174575535641201201812012018Copyright ©; 2017, Bobkova I.N., Каkhsurueva P.A., Stavrovskaya E.V., Filatova E.E.Copyright ©; 2017, Бобкова И.Н., Кахсуруева П.А., Ставровская Е.В., Филатова Е.Е.2017Bobkova I.N., Каkhsurueva P.A., Stavrovskaya E.V., Filatova E.E.Бобкова И.Н., Кахсуруева П.А., Ставровская Е.В., Филатова Е.Е.https://creativecommons.org/licenses/by/4.0https://almclinmed.ru/jour/article/view/644

Membranous nephropathy (MN) is the leading cause of nephrotic syndrome in adults. This review describes a 60-year history of MN study and represents an evolution in the understanding of its pathogenesis from experimental models to the clinic. Due to the development in 1959 of an MN animal model (active and passive Heymann's nephritis) the renal autoantigen podocyte-related protein megalin was identified. Experimental studies confirmed that the immune deposits consisting of megalin with circulating antimegalin antibodies are formed in situ. That leads to the complement activation providing with the membrane attack complex formation in the subepithelial space which causes a  sub-lethal podocyte injury with a  reorganization of their actin cytoskeleton and a  dissociation of slit diaphragm proteins. As the result, the permeability of the filtration barrier increases leading to the proteinuria. Thus, the understanding of an idiopathic MN pathogenesis evolved from an immune complex-mediated damage into a podocytopathy so the pathway for the other podocyte-related antigens search was opened. Mechanisms of podocytes damage were considered to be the leading ones in the human idiopathic MN development. Nevertheless, the searching for antigenic targets different from the megalin was continued for many years, as human podocytes do not express this protein. In the first decade of the 21st century such autoantigens as neutral endopeptidase, M-type phospholipase A2 receptor, and thrombospondin type-1 domain-containing 7A were identified. Furthermore, the leading role of autoantibodies directed against these podocyte targets was confirmed. New knowledge formed the basis for modern diagnostics and treatment methods of MN. 

Мембранозная нефропатия (МН)  – наиболее частая причина развития нефротического синдрома у  взрослых. В  обзоре отражена более чем 60-летняя история изучения данного заболевания, представлена эволюция в понимании его патогенеза  – от эксперимента к  клинике. Благодаря созданию в  1959 г. животной модели МН (активный и  пассивный Хеймановский нефрит) был идентифицирован почечный аутоантиген  – белок мегалин, экспрессируемый в  ножковых отростках подоцитов. В  ходе экспериментальных исследований подтверждено формирование иммунных комплексов in situ из циркулирующих антител к  мегалину, что ведет к  активации комплемента с  образованием в  субэпителиальном пространстве мембраноатакующего комплекса, вызывающего сублетальное повреждение подоцитов с  реорганизацией их актинового цитоскелета, диссоциацией белков щелевидной диафрагмы, приводящих к  увеличению проницаемости фильтрационного барьера и  развитию протеинурии. Так понимание природы идиопатической МН эволюционировало от иммуно-комплексного гломерулярного повреждения к  подоцитопатии, и  был открыт путь для поиска других подоцитсвязанных антигенов. Механизмы подоцитарного повреждения были признаны ключевыми в  развитии идиопатической МН и у человека, но в течение многих лет проводился поиск отличных от мегалина антигенных мишеней, поскольку человеческие подоциты этот белок не экспрессируют. В первом десятилетии XXI в. такие аутоантигены были идентифицированы  – нейтральная эндопептидаза, трансмембранный М-типа рецептор фосфолипазы А2, домен тромбоспондина 1-го типа, содержащий 7А, – и установлена ведущая роль аутоантител, направленных на эти подоцитарные мишени. Новые знания легли в  основу создания современных методов диагностики и лечения МН. 

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