Современные представления о первичном фокальном сегментарном гломерулосклерозе у взрослых: патогенез и подходы к лечению. Обзор литературы

Введение: первичный фокальный сегментарный гломерулосклероз является морфологическим вариантом нефропатии, в основе которой лежит повреждение подоцитов. Патогенез первичного ФСГС изучается с 90-х годов, однако полностью не расшифрован до настоящего времени. Вместе с тем, накоплено большое количество данных, позволяющих сформулировать определенную концепцию развития заболевания. Цель настоящего обзора представить современный взгляд на патогенез и подходы к терапии первичного ФСГС у взрослых. Основные сведения: в обзоре представлен современный взгляд на патогенез первичного фокального сегментарного гломерулосклероза. Обсуждается роль подоцитов и париетальных эпителиальных клеток в формировании очагов склероза и прогрессировании заболевания. Особое внимание уделено предполагаемым молекулам-кандидатам на роль циркулирующих факторов проницаемости: растворимого рецептора активатора плазминогена (suPAR), кардиотрофин-подобного фактора-1 (CLCF-1), CD80 (B7-1) и механизмам их действия. Повышенный уровень этих факторов выявляют в сыворотке крови и на поверхности подоцитов у больных ФСГС. Согласно современной концепции, патогенез первичного ФСГС связан с нарушением адаптивного иммунного ответа. Представлены данные о том, что дисбаланс определенных Т-клеточных подклассов участвует в патогенезе заболевания. Повышение Th17 лимфоцитов и снижение количества Т-регуляторных клеток может оказаться решающим для развития первичного ФСГС. Имеет также значение активация В-клеток, о чем свидетельствуют непосредственное влияние В-лимфоцитов на развитие протеинурии, выявление циркулирующих антител и эффективность применения ритуксимаба у больных с ФСГС. Обсуждается возможная роль анти-CD40-антител и антител к убиквитин карбоксильной гидролазе L1 в развитии первичного ФСГС. Прямо или через продукцию факторов проницаемости эти механизмы ведут к повреждению подоцитов. В отдельном разделе представлен алгоритм иммуносупрессивной терапии: глюкокортикостероидов и цитостатиков. Рассмотрены перспективы терапии ФСГС с учетом предполагаемых патогенетических механизмов заболевания.

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