Значение малобелковой диеты и препаратов кетоаналогов незаменимых аминокислот в контроле над карбамилированием белков и токсическими эффектами мочевины при хронической болезни почек

Михайлова Н.А. Значение малобелковой диеты и препаратов кетоаналогов незаменимых аминокислот в контроле над карбамилированием белков и токсическими эффектами мочевины при хронической болезни почек. Терапевтический архив. 2021; 93 (6): 729–735. DOI: 10.26442/00403660.2021.06.200915

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Mikhailova NA. The value of a low-protein diet and ketoanalogues of essential amino acids in the сontrol of protein carbamylation and toxic effects of urea in chronic kidney disease. Terapevticheskii Arkhiv (Ter. Arkh). 2021; 93 (6): 729–735. DOI: 10.26442/00403660.2021.06.200915

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Аннотация

Хроническая болезнь почек (ХБП) характеризуется высокой смертностью от сердечно-сосудистых заболеваний, развитию которых способствуют как традиционные факторы риска (характерные для общей популяции), так и нетрадиционные (специфичные для пациентов с ХБП).
К числу таких факторов относятся уремические токсины, для которых установлена причинно-следственная взаимосвязь с конкретными патологическими процессами у пациентов с ХБП, в том числе с формированием сосудистой дисфункции и ускоренным прогрессированием атеросклероза. Мочевина долгое время рассматривалась не в качестве уремического токсина, а как маркер метаболического дисбаланса или эффективности диализа (Kt/V) у пациентов с ХБП. В последние годы появляется все больше публикаций, посвященных изучению токсических эффектов мочевины с развитием токсико-уремических осложнений и фенотипа преждевременного старения, распространенного при ХБП. Установлено, что повышение уровней мочевины при уремическом синдроме вызывает повреждение эпителиального барьера кишечника с транслокацией бактериальных токсинов в кровоток и развитием системного воспаления, провоцирует апоптоз клеток гладкой мускулатуры сосудов, а также эндотелиальную дисфункцию, что напрямую способствует развитию сердечно-сосудистых осложнений.
Опосредованные эффекты повышенного содержания мочевины связаны с реакциями карбамилирования, когда изоциановая кислота (продукт катаболизма мочевины) изменяет структуру и функцию белков в организме. Карбамилирование белков у пациентов с ХБП связано с развитием фиброза почек, атеросклероза и анемии. Таким образом, мочевина сегодня рассматривается в качестве важного негативного агента в патогенезе осложнений при ХБП. Исследования, посвященные изучению малобелковой диеты с назначением препаратов кетоаналогов незаменимых аминокислот в целях минимизации накопления мочевины и других уремических токсинов, демонстрируют клиническую пользу такого вмешательства в плане замедления прогрессирования ХБП и развития сердечно-сосудистых осложнений.

Ключевые слова: уремические токсины, мочевина, карбамилирование белков, малобелковая диета, кетоаналоги аминокислот, хроническая болезнь почек

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Chronic kidney disease (CKD) is characterized by high mortality from cardiovascular diseases, the development of which is facilitated by traditional risk factors (typical for the general population) and by nontraditional ones (specific to patients with CKD) as well. These factors include also uremic toxins, for which a causal relationship has been established with specific pathological processes in patients with CKD, comprising the development of vascular dysfunction and accelerated progression of atherosclerosis. Urea has long been considered not as a uremic toxin, but as a marker of metabolic imbalance or dialysis efficiency (Kt/V) in CKD patients. In recent years, more and more publications have appeared on the study of the toxic effects of urea with the development of toxic-uremic complications and the phenotype of premature aging, common in CKD. It was found that an increase in urea levels in uremic syndrome causes damage to the intestinal epithelial barrier with translocation of bacterial toxins into the bloodstream and the development of systemic inflammation, provokes apoptosis of vascular smooth muscle cells, as well as endothelial dysfunction, which directly contributes to the development of cardiovascular complications. The indirect effects of increased urea levels are associated with carbamylation reactions, when isocyanic acid (a product of urea catabolism) changes the structure and function of proteins in the body. Carbamylation of proteins in CKD patients is associated with the development of renal fibrosis, atherosclerosis and anemia. Thus, urea is now regarded as an important negative agent in the pathogenesis of complications in CKD. Studies on a low-protein diet with using ketoanalogues of essential amino acids to minimize the accumulation of urea and other uremic toxins demonstrate the clinical benefit of such an intervention in slowing the progression of CKD and the development of cardiovascular complications.

Keywords: uremic toxins, urea, protein carbamylation, low protein diet, ketoanalogues of amino acids, chronic kidney disease

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Авторы

Н.А. Михайлова*

ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России, Москва, Россия
*natmikhailova@mail.ru

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Nataliia A. Mikhailova*

Russian Medical Academy of Continuous Professional Education, Moscow, Russia
*natmikhailova@mail.ru

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