Исследование генетических причин врожденного и инфантильного нефротического синдрома у российских детей

Актуальность: врожденный и инфантильный нефротический синдром (ВНС и ИНС соответственно) - особые группы стероид-резистентного нефротического синдрома, подбор терапии в которых вызывает наибольшие трудности, а прогрессирование до 5-й стадии хронической болезни почек (ХБП 5 ст.) имеет неизбежный характер. Ранее опубликованные исследования генетических причин развития ВНС и ИНС в РФ выполнены на крайне малых выборках. Цель: изучение генетических причин ВНС и ИНС у российских детей. Методы: на базе нефрологического отделения ФГАУ «НМИЦ здоровья детей» Минздрава РФ проведено двунаправленное исследование, включившее 43 ребенка с ВНС и ИНС, которые наблюдались в отделении с 2010 по 2020 годы. Всем детям методом секвенирования нового поколения выполнено исследование таргентных областей 57 генов, патогенные варианты в которых описаны у пациентов с симптомокомплексом НС. Результаты. Среди морфологических типов превалировал фокально-сегментарный гломерулосклероз (50%) вне зависимости от выявленного патогенного варианта. У 38 (88,4%) детей выявлены мутации в генах NPHS2 (37,2%), NPHS1 (13,9%), WT1 (9,3%), CUBN (7,0%), PLCE1 и LMX1B (по 4,7%), SMARCAL1, CRB2, KANK2, COQ6 и CFH (по 2,3%, соответственно). На фоне терапии циклоспорином А у 18,5% из 27 детей отмечена частичная либо полная ремиссия, имеющая нестойкий характер. Хроническая болезнь почек 5-й стадии за период наблюдения достигнута у 15 (34,9%) детей в возрасте 4 года 11 месяцев ± 3 г. 3 мес. Трансплантация почки проведена 11 пациентам, годичная выживаемость трансплантата составила 82%. Выводы: проведение молекулярно-генетического исследования у детей с дебютом нефротического синдрома на первом году жизни более информативно в отношении выбора терапевтической тактики и оценки прогноза, чем инвазивный метод - пункционная нефробиопсия. Проведение трансплантации почки в описанной группе детей перспективно в связи с низкими рисками возврата заболевания в трансплантат.

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