Основные механизмы поражения почек при гиперурикемии

Гиперуркемию (ГУ) обычно обсуждают с точки зрения риска развития подагры, при этом даже в отсутствие приступов подагрического артрита она может сочетаться с большим числом коморбидных состояний, среди которых особое место занимают заболевания почек. Результаты крупных исследований и их мета-анализ свидетельствуют в пользу связи развития патологии почек и прогрессирования уже имеющейся ХБП у больных с ГУ.

Механизмы ГУ-опосредованного повреждения почек сложны и включают в себя прямое повреждение почек кристаллами МК, ГУ-индуцированные воспалительный ответ, оксидативный стресс, эндотелиальную дисфункцию, которые дополняя и усиливая друг друга ведут в итоге к развитию гломерулосклероза и тубулоинтерстициального фиброза. Ключевым звеном развития воспалительного ответа является активация криопириновой инфламмасомы, ведущая к гиперпродукции интерлейкина-1, что позволяет рассматривать ГУ в качестве аутовоспалительного заболевания. При этом, в настоящее время доказано, что наряду с кристаллами моноурата натрия и растворимая форма МК также способна активировать инфламмасому.

Изучение эволюции обмена МК у животных и путей внутриклеточного распада пуринов, в результате которого и образуется МК, позволяют предположить, что действующим патогеном является не столько ГУ, сколько внутриклеточная гиперконцентрация мочевой кислоты (гиперурикоцитоз), которая является «сигналом тревоги» и запускает аутовоспалительные реакции. Таким образом, ГУ наряду с традиционным фактором повреждения внутренних органов, можно рассматривать в качестве маркера уже реализовавшегося повреждения в клетках врожденного иммунитета (воспалительные макрофаги и нейтрофилы). Это понимание позволяет пересмотреть подходы к терапии, делая акцент, в первую очередь на противовоспалительных препаратах – колхицине и/или ингибиторах интерлейкина-1.

Дальнейшее изучение молекулярных механизмов влияния ГУ и их понимание патофизиологических процессов сделает возможным определение подходов к ранней диагностике почечной патологии при ГУ и оптимизацию методов лечения таких пациентов.

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