References

nid

Нефрология и диализ

Nephrology and Dialysis

1680-44222618-9801

Российское диализное общество

10.28996/2618-9801-2021-1-57-72

nid-8

Research Article

ОРИГИНАЛЬНЫЕ СТАТЬИ

ORIGINAL ARTICLES

Исследование генетических причин врожденного и инфантильного нефротического синдрома у российских детей

A study of genetic causes of congenital and infantile nephrotic syndrome in children of Russian Federation

Милованова

А. М.

Milovanova

A. M.

milovanova.am@nczd.ru

Пушков

А. А.

Pushkov

A. A.

noemail@neicon.ru

Савостьянов

К. В.

Savostyanov

K. V.

noemail@neicon.ru

Зробок

О. И.

Zrobok

O. I.

noemail@neicon.ru

Вашурина

Т. В.

Vashurina

T. V.

noemail@neicon.ru

Ананьин

П. В.

Ananin

P. V.

noemail@neicon.ru

Столяревич

Е. С.

Stolyarevich

E. S.

noemail@neicon.ru

Фисенко

А. П.

Fisenko

A. P.

noemail@neicon.ru

Цыгин

А. Н.

Tsygin

A. N.

noemail@neicon.ru

ФГАУ «Национальный медицинский исследовательский центр здоровья детей» Министерства Здравоохранения Российской ФедерацииРоссияNational Medical Research Center for Children's HealthRussian Federation

ГБУЗ «ГКБ № 52» ДЗМРоссияCity Clinical Hospital No. 52Russian Federation

2021

21062024

2315772

2024

Милованова А.М., Пушков А.А., Савостьянов К.В., Зробок О.И., Вашурина Т.В., Ананьин П.В., Столяревич Е.С., Фисенко А.П., Цыгин А.Н.

Milovanova A.M., Pushkov A.A., Savostyanov K.V., Zrobok O.I., Vashurina T.V., Ananin P.V., Stolyarevich E.S., Fisenko A.P., Tsygin A.N.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://journal.nephro.ru/jour/article/view/8

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.

Relevance: congenital and infantile nephrotic syndrome (CNS and INS respectively) are special groups of steroid-resistant nephrotic syndrome, in which progression to the end-stage kidney disease is unavoidable and therapy selection is rather difficult. Studies of the genetic causes of the CNS and INS existing in Russia had been performed on extremely small groups. Purpose: the study of genetic causes in CNS and INS in Russian children. Methods: an ambidirectional study based on the nephrology department of FSAI “National medical research center for children’s health” included 43 children with CNS and INS. All children underwent genetic testing of 57 genes target regions by the new generation sequencing. Pathogenic variants in these gene regions were found to be associated with nephrotic syndrome. Results: among the morphological variants, focal-segmental glomerulosclerosis prevailed (50%) regardless of the pathogenic variant. In 38 children, mutations were identified in the genes NPHS2 (37.2%), NPHS1 (13.9%), WT1 (9.3%), CUBN (7.0%), PLCE1 and LMX1B (4.7% each), SMARCAL1, CRB2, KANK2, COQ6, CFH (2.3% each). During therapy with cyclosporine A, 18.5% of 27 children showed a partial or complete unstable remission. Over the period of observation 15 children (34.9%) reached end-stage kidney disease, the average age was 4 years 11 month ± 3 years 3 month. Kidney transplantation was performed in 11 patients; the one-year graft survival rate was 82%. Conclusions: conducting a molecular genetic study in children with the onset of nephrotic syndrome in the first year of life is more informative to the choice of treatment tactics and evaluating of prognosis than the invasive method - nephrobiopsy. Kidney transplantation in these groups is rather perspective in cause of the low risk of recurrence.

нефротический синдромврожденный нефротический синдроминфантильный нефротический синдромстероид-резистентный нефротический синдромгенетические факторыпатогенные вариантыдетиnephrotic syndromecongenital nephrotic syndromeinfantile nephrotic syndromesteroid-resistant nephrotic syndromegenetic factorspathogenic variantschildren

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The authors declare that there are no conflicts of interest present.