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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">nefr</journal-id><journal-title-group><journal-title xml:lang="ru">Нефрология</journal-title><trans-title-group xml:lang="en"><trans-title>Nephrology (Saint-Petersburg)</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1561-6274</issn><issn pub-type="epub">2541-9439</issn><publisher><publisher-name>Pavlov First Saint-Petersburg State Medical University</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.36485/1561-6274-2024-28-3-47-54</article-id><article-id custom-type="edn" pub-id-type="custom">PXVWTH</article-id><article-id custom-type="elpub" pub-id-type="custom">nefr-2334</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ СТАТЬИ. КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL ARTICLES. CLINICAL INVESTIGATIONS</subject></subj-group></article-categories><title-group><article-title>Нарушение гомеостаза цитруллина у пациентов с артериальной гипертензией</article-title><trans-title-group xml:lang="en"><trans-title>Disturbances of citrulline homeostasis in patients with arterial hypertension</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0605-7617</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Жлоба</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Zhloba</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Проф. Жлоба Александр Анатольевич, д-р мед. наук, НОИ биомедицины, руководитель отдела биохимии</p><p>197022, Санкт-Петербург, ул. Л. Толстого, д. 6–8, корп. 3</p><p>Тел.: (812)338-71-08</p></bio><bio xml:lang="en"><p>Prof. Aleksandr A. Zhloba, MD, PhD, DMedSci, Scientific Research Institute of Biomedicine, Head of the Department of Biochemistry</p><p>197022, St-Petersburg, L. Tolstoy st., 6-8, build 3</p><p>Phone: (812)338-71-08</p></bio><email xlink:type="simple">zhlobaaa@1spbgmu.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2278-8391</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Субботина</surname><given-names>Т. Ф.</given-names></name><name name-style="western" xml:lang="en"><surname>Subbotina</surname><given-names>T. F.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Доц. Субботина Татьяна Федоровна, д-р мед. наук, НОИ биомедицины, заведующая лабораторией биохимического мониторинга</p><p>197022, Санкт-Петербург, ул. Л. Толстого, д. 6–8, корп. 3</p><p>Тел.: (812)338-71-08</p></bio><bio xml:lang="en"><p>Associate prof. Tatiana F. Subbotina, MD, PhD, DMedSci, Scientific Research Institute of Biomedicine, Head of the Laboratory of Biochemical Monitoring</p><p>197022, St-Petersburg, L. Tolstoy st., 6-8, build 3</p><p>Phone: (812)338-71-08</p></bio><email xlink:type="simple">subbotina2002@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Pavlov First Saint Petersburg State Medical University</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>19</day><month>09</month><year>2024</year></pub-date><volume>28</volume><issue>3</issue><fpage>47</fpage><lpage>54</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Жлоба А.А., Субботина Т.Ф., 2024</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="ru">Жлоба А.А., Субботина Т.Ф.</copyright-holder><copyright-holder xml:lang="en">Zhloba A.A., Subbotina T.F.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://journal.nephrolog.ru/jour/article/view/2334">https://journal.nephrolog.ru/jour/article/view/2334</self-uri><abstract><p>ВВЕДЕНИЕ. Определение уровня цитруллина (Цит) в крови позволяет диагностировать нарушения метаболизма белка в проксимальных канальцах почек. Ранее нами показано, что нарушение метаболической функции почек при артериальной гипертензии (АГ) выражается повышением уровня Цит. ЦЕЛЬ заключалась в определении диагностически значимых порогов превышения уровней Цит в крови отдельно для мужчин и для женщин с АГ. ПАЦИЕНТЫ И МЕТОДЫ. Обследовано 115 пациентов с АГ при расчетной скорости клубочковой фильтрации более 45 мл/мин/1,73 м2, из них – 44 мужчины и 71 женщина в возрасте 63 [56; 68] и 64 [53; 73] лет соответственно. В группе сравнения было 30 доноров старшего возраста (11 мужчин и 19 женщин). Определение уровней Цит, аргинина (Арг) и других проводили методом высокоэффективной жидкостной хроматографии. РЕЗУЛЬТАТЫ. Нарушения обмена веществ отмечались в виде ожирения у 57 % мужчин и 50 % женщин, а также гиперхолестеринемии – у 30 и 33 % и гипертриглицеридемии – у 37 и 29 % соответственно. Уровень Цит в плазме крови был повышен в среднем у мужчин на 32 % и у женщин на 29 %. При проведении ROC-анализа определена величина порога отсечения Цит: для мужчин – более 49,1 мкМ (р = 0,0023) при 68 % чувствительности и 91 % специфичности и для женщин – 46,3 мкМ (p= 0,0014) при чувствительности 80 % и специфичности 63 %. ЗАКЛЮЧЕНИЕ. Незначительное снижение метаболической функции почек отражается на гомеостазе Цит, что имеет диагностическое значение. По полученным данным почечный метаболизм обеспечивает содержание Цит в крови не выше 49,1 мкМ у мужчин и 46,3 мкМ у женщин до наступления нарушения этой метаболической функции у пациентов с АГ.</p></abstract><trans-abstract xml:lang="en"><p>BACKGROUND. Evaluation the level of citrulline (Cit) in the blood allows us to determine metabolic disorders in the proximal tubules of the kidneys. Previously, we showed that impaired metabolic function of the kidneys in hypertensive patients (AH) is expressed by an increase in the level of Cit. THE AIM was to determine diagnostically significant Cutoff value or exceeding Cit levels in the blood separately for men and women with hypertension. PATIENTS AND METHODS. We examined 115 hyperten sive patients with an estimated glomerular filtration rate ≥ 45 ml/min/1.73 m2, included 44 men and 71 women aged 63 [56; 68] and 64 [53; 73] years, respectively. The comparison group included 30 older age group donors (11 men and 19 women). Determination of the levels of Cit, arginine (Arg) and others was carried out using high-performance liquid chromatography. RESULTS. Metabolic disorders: obesity – noted in 57 % of men and 50 % of women; and hypercholesterolemia in 30 and 33 % and hypertriglyceridemia in 37 and 29 % of patients, respectively. Metabolic dysfunction in the subgroups of men and women, according to Cit content, was expressed by an increase in its levels by an average of 32 and 29 %, respectively. ROC analysis determined the cutoff value for men &gt; 49.1 μM Cit, p = 0.0023, which corresponds to 68 % sensitivity and 91 % specificity, and 46.3 μM (p = 0.0014) with 80 % sensitivity and specificity 63 % for women. CONCLUSION. A slight decrease in the metabolic functions of the kidneys affects Cit homeostasis, which has diagnostic value. According to the data obtained, renal metabolism ensures the content of Cit in the blood – not higher than 49.1 μM in men and women – 46.3 μM, before the onset of a violation of this metabolic function in patients with hypertension.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>хроническая болезнь почек</kwd><kwd>цитруллин</kwd><kwd>аргинин</kwd><kwd>почка</kwd><kwd>артериальная гипертензия</kwd><kwd>мужчины и женщины</kwd></kwd-group><kwd-group xml:lang="en"><kwd>chronic kidney disease</kwd><kwd>citrulline</kwd><kwd>arginine</kwd><kwd>kidney</kwd><kwd>arterial hypertension</kwd><kwd>men and women</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Авторы выражают благодарность менеджменту ПСПбГМУ им. акад. И.П. Павлова за поддержку в организации исследования.  Исследование выполнено в рамках государственного задания.</funding-statement><funding-statement xml:lang="en">The authors express their gratitude to the management of Pavlov First Saint Petersburg State Medical University for support in organizing the study. The study was carried out within the framework of a state assignment.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Балашова ЕЕ, Трифонова ОП, Маслов ДЛ и др. Метаболомное профилирование в изучении процессов старения. Биомед анализ 2022;68(5):321–338. doi: 10.18097/PBMC20226805321</mixed-citation><mixed-citation xml:lang="en">Balashova EE, Trifonova OP, Maslov DL et al. Metabolome profiling in the study of aging processes. Biomed Khim 2022;68(5):321–338. (In Russ.) doi: 10.18097/PBMC20226805321</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Cañadas-Garre M, Anderson K, McGoldrick J et al. Proteomic and metabolomic approaches in the search for biomarkers in chronic kidney disease. J Proteomics 2019;193:93–122. doi: 10.1016/j.jprot.2018.09.020</mixed-citation><mixed-citation xml:lang="en">Cañadas-Garre M, Anderson K, McGoldrick J et al. Proteomic and metabolomic approaches in the search for biomarkers in chronic kidney disease. J Proteomics 2019;193:93–122. doi: 10.1016/j.jprot.2018.09.020</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Gervasini G, Verde Z, González LM et al. Prognostic significance of amino acid and biogenic amines profiling in chronic kidney disease. Biomedicines 2023;11(10):2775. doi: 10.3390/biomedicines11102775</mixed-citation><mixed-citation xml:lang="en">Gervasini G, Verde Z, González LM et al. Prognostic significance of amino acid and biogenic amines profiling in chronic kidney disease. Biomedicines 2023;11(10):2775. doi: 10.3390/biomedicines11102775</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Yin Y, Shan C, Han Q et al. Causal effects of human serum metabolites on occurrence and progress indicators of chronic kidney disease: a two-sample Mendelian randomization study. Front Nutr 2024;10:1274078. doi: 10.3389/fnut.2023.1274078</mixed-citation><mixed-citation xml:lang="en">Yin Y, Shan C, Han Q et al. Causal effects of human serum metabolites on occurrence and progress indicators of chronic kidney disease: a two-sample Mendelian randomization study. Front Nutr 2024;10:1274078. doi: 10.3389/fnut.2023.1274078</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Korol L, Stepanova N, Vasylchenko V. #612 Serum citrulline level is associated with oxidative stress and chronic kidney disease progression. Nephr Dial Transpl 2024;39(Suppl_1):gf ae069–1382–612. doi: 10.1093/ndt/gfae069.1382</mixed-citation><mixed-citation xml:lang="en">Korol L, Stepanova N, Vasylchenko V. #612 Serum citrulline level is associated with oxidative stress and chronic kidney disease progression. Nephr Dial Transpl 2024;39(Suppl_1):gf ae069–1382–612. doi: 10.1093/ndt/gfae069.1382</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Rabier D, Kamoun P. Metabolism of citrulline in man. Amino Acids 1995;9:299–316. doi: 10.1007/BF00807268</mixed-citation><mixed-citation xml:lang="en">Rabier D, Kamoun P. Metabolism of citrulline in man. Amino Acids 1995;9:299–316. doi: 10.1007/BF00807268</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Aguayo E, Martínez-Sánchez A, Fernández-Lobato B, Alacid F. L-citrulline: a non-essential amino acid with important roles in human health. Appl Sci 2021;11(7):3293. doi: 10.3390/app11073293</mixed-citation><mixed-citation xml:lang="en">Aguayo E, Martínez-Sánchez A, Fernández-Lobato B, Alacid F. L-citrulline: a non-essential amino acid with important roles in human health. Appl Sci 2021;11(7):3293. doi: 10.3390/app11073293</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Pillai SM, Seebeck P, Fingerhut R et al. Kidney mass reduction leads to l-arginine metabolism-dependent blood pressure increase in mice. J Am Heart Assoc 2018;7(5):e008025. doi: 10.1161/JAHA.117.008025</mixed-citation><mixed-citation xml:lang="en">Pillai SM, Seebeck P, Fingerhut R et al. Kidney mass reduction leads to l-arginine metabolism-dependent blood pressure increase in mice. J Am Heart Assoc 2018;7(5):e008025. doi: 10.1161/JAHA.117.008025</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Chen GF, Baylis C. In vivo renal arginine release is impaired throughout development of chronic kidney disease. Am J Physiol Renal Physiol 2010;298(1):F95–102. doi: 10.1152/ajprenal.00487.2009</mixed-citation><mixed-citation xml:lang="en">Chen GF, Baylis C. In vivo renal arginine release is impaired throughout development of chronic kidney disease. Am J Physiol Renal Physiol 2010;298(1):F95–102. doi: 10.1152/ajprenal.00487.2009</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Brosnan ME, Brosnan JT. Renal arginine metabolism. J Nutr 2004;134(10 Suppl):2791S–2795S; discussion 2796S–2797S. doi: 10.1093/jn/134.10.2791S</mixed-citation><mixed-citation xml:lang="en">Brosnan ME, Brosnan JT. Renal arginine metabolism. J Nutr 2004;134(10 Suppl):2791S–2795S; discussion 2796S–2797S. doi: 10.1093/jn/134.10.2791S</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Жлоба АА, Субботина ТФ, Рейпольская ТЮ. Уровень цитруллина крови у пациентов с артериальной гипертензией и нарушением экскреторной функции почек. Клин лаб диагн 2023;68(3):133–140. doi: 10.51620/0869-2084-2023-68-3-133-140</mixed-citation><mixed-citation xml:lang="en">Zhloba AA, Subbotina TF, Reypolskaya TYu. The level of blood citrulline in hypertensive patients with abnormal renal excretory function. Klin Lab Diagn 2023;68(3):133–140. (In Russ.) doi: 10.51620/0869-2084-2023-68-3-133-140</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Жлоба АА, Субботина ТФ, Шипаева КА. Способ определения содержания гомоаргинина в плазме крови и других биологических жидкостях человека. Патент РФ. № 2609873; 2017</mixed-citation><mixed-citation xml:lang="en">Zhloba AA, Subbotina TF, Shipaeva KA. The way for determining the content of homoarginine in blood plasma and other biological fluids of human. Patent RF N 2609873; 2017. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Zhloba AA, Subbotina TF. Homocysteinylation score of high molecular weight plasma proteins. Amino Acids 2014;46(4):893–899. doi: 10.1007/s00726-013-1652-4</mixed-citation><mixed-citation xml:lang="en">Zhloba AA, Subbotina TF. Homocysteinylation score of high molecular weight plasma proteins. Amino Acids 2014;46(4):893–899. doi: 10.1007/s00726-013-1652-4</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Тиц Н.У, ред. Клиническая оценка лабораторных тестов: Справочник (пер. с англ.). Медицина, М., 1986</mixed-citation><mixed-citation xml:lang="en">Tietz NW, ed. Clinical Guide to Laboratory Tests. WB Saunders, Philadelphia, 1983. (In Russ.)</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Жлоба АА, Субботина ТФ. Оценка фолатного статуса с использованием общего гомоцистеина у пациентов с гипертонической болезнью. Рос мед журн 2019;25(3):158–165. doi: 10.18821/0869-2106-2019-25-3-158-165</mixed-citation><mixed-citation xml:lang="en">Zhloba AA, Subbotina TF. The evaluation of folate status using total homocysteine in hypertensive patients. Ross med zhurn 2019;25(3):158–165. (In Russ.) doi: 10.18821/0869-2106-2019-25-3-158-165</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Rougé C, Des Robert C, Robins A et al. Manipulation of citrulline availability in humans. Am J Physiol Gastrointest Liver Physiol 2007;293(5):G1061–7. doi: 10.1152/ajpgi.00289.2007</mixed-citation><mixed-citation xml:lang="en">Rougé C, Des Robert C, Robins A et al. Manipulation of citrulline availability in humans. Am J Physiol Gastrointest Liver Physiol 2007;293(5):G1061–7. doi: 10.1152/ajpgi.00289.2007</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
