nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.36485/1561-6274-2024-28-4-45-54REGNVCnefr-2351Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ. КЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯORIGINAL ARTICLES. CLINICAL INVESTIGATIONSПрогностическое значение сывороточного уровня белка Klotho в оценке: сердечно-сосудистого риска, достижения терминальной стадии ХБП и общей выживаемости больных с исходной ХБП С3-4: проспективный клинический анализ (период наблюдения 8 лет)Predictive value of serum Klotho protein level in assessing: cardiovascular risk, achievement of the end stage of CKD, and overall survival of patients with initial CKD C3-4: a prospective clinical analysis (follow-up period of 8 years)https://orcid.org/0000-0002-5599-0350МиловановаЛ. Ю.MilovanovaL. Yu.

Проф. Милованова Людмила Юрьевна, д-р мед. наук,  кафедра внутренних,  профессиональных  болезней  и  ревматологии

119048, Москва, ул. Трубецкая, д. 8, стр. 2. 

Prof. Ludmila Yu. Milovanova, MD, PhD, DMedSci,  Department  of  Internal,  Occupational  Diseases and Rheumatology

119048, Russia, Moscow, Trubetskaya st. 8, build. 2

ludm.milovanova@gmail.comhttps://orcid.org/0000-0002-1873-0189ВолковА. В.VolkovA. V.

Доц. Волков Алексей Владимирович, канд. мед. наук, кафедра психиатрии   и   наркологии

119048, Москва, ул. Трубецкая, д. 8, стр. 2. 

Associate professor Alexey V. Volkov, MD, PhD, Department of psychiatry and narcology

119048, Russia, Moscow, Trubetskaya st. 8, build. 2

a-1973b@yandex.ruhttps://orcid.org/0000-0002-2687-6161МиловановаС. Ю.MilovanovaS. Ya.

Проф. Милованова Светлана Юрьевна, д-р мед. наук, кафедра внутренних, профессиональных болезней и ревматологии

119048, Москва, ул. Трубецкая, д. 8, стр. 2. 

Prof. Svetlana Yu. Milovanova, MD, PhD, DMedSci, Department of Internal, Occupational Diseases and Rheumatology

119048, Russia, Moscow, Trubetskaya st. 8, build. 2

s.y.milovanova@gmail.comhttps://orcid.org/0000-0002-7363-6195ТарановаМ. В.TaranovaM. V.

Доц. Таранова Марина Владимировна, канд. мед. наук, кафедра внутренних,  профессиональных  болезней  и  ревматологии

119048, Москва, ул. Трубецкая, д. 8, стр. 2. 

Associate professor Marina V. Taranova, MD, PhD, Department of associate professor of the Department of Internal, Occupational Diseases and Rheumatology

119048, Russia, Moscow, Trubetskaya st. 8, build. 2

mvtaranova@mail.ruhttps://orcid.org/0000-0001-9558-363XНеждановК. С.NezhdanovK. S.

Аспирант Нежданов Кирилл Сергеевич, кафедра внутренних болезней 

119991, Москва, Ленинские горы, д. 1, строение 13

Postgraduate student Kirill S. Nezhdanov, MD, Department of Internal Diseases

119991 Russia, Moscow Leninskie Gory st. 1 build. 13

cyril.nezhdanov@gmail.comПервый Московский государственный медицинский университет им. И.М. СеченоваРоссияSechenov UniversityRussian FederationМосковский государственный университет им. М.В. ЛомоносоваРоссияMoscow State UniversityRussian Federation2024170120252844554Copyright © Милованова Л.Ю., Волков А.В., Милованова С.Ю., Таранова М.В., Нежданов К.С., 20252025Милованова Л.Ю., Волков А.В., Милованова С.Ю., Таранова М.В., Нежданов К.С.Milovanova L.Y., Volkov A.V., Milovanova S.Y., Taranova M.V., Nezhdanov K.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/2351ВВЕДЕНИЕ

ВВЕДЕНИЕ. Сердечно-сосудистые осложнения (ССО) являются ведущей причиной смертности в когорте больных с ХБП, в том числе, среди лиц молодого, трудоспособного возраста. Поиск прогностического маркера, позволяющего предсказать и предупредить риск ССО, является важной не только медицинской, но и социально-экономической задачей. ЦЕЛЬ

ИССЛЕДОВАНИЯ

ИССЛЕДОВАНИЯ. Определить прогностическое значение исходного сывороточного уровня Клото в оценке сердечно-сосудистого риска, риска развития терминальной почечной недостаточности (ТХПН) и общей выживаемости среди больных с ХБП 3–4 стадий в течение 8-летнего периода наблюдения.

ПАЦИЕНТЫ И МЕТОДЫ

ПАЦИЕНТЫ И МЕТОДЫ. В исследование включено 75 больных с ХБП С3–4, средний возраст – 54±9 лет. Исходный сывороточный уровень Клото был разделен на квартили (1-й квартиль Клото – 148–336 пг/мл; 2–3-й квартиль – 337–580 пг/мл; 4-й квартиль – 580– 812 пг/мл). Оценены общая выживаемость больных за период 8 лет, причина смерти, достижение ТХПН в зависимости от квартиля Клото.

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ. За период наблюдения умерли 22 больных, из них от ССО – 12 (54,5 %), от ковидной инфекции – 7 (31,8 %), от других причин – 3 (13,6 %). При оценке по квартилям среди умерших пациентов преобладали больные с 1-м квартилем, в том числе – от ССО: 1-й квартиль составил – 9 (75,0 %), 2–3-й квартиль – 3 (25,0 %), 4-й квартиль – 0 (0 %) (хи-квадрат = 8,2, р=0,023). Среди больных, достигших ТХПН и начала диализа (n=30), пациенты с 1-м квартилем составили 12 (63,2 %), с 2–3-м квартилем –16 (43,2 %), 4-м квартилем – 2 (10,5 %) (хи-квадрат =11,3, p=0,01). Среди выживших больных (n=53), имеющих ССО на момент окончания наблюдения (n=28), пациенты с 1-м квартилем составили 19 (67,9 %), 2–3-м квартилем 9 (32,1 %), 4-м квартилем – 0 % (хи-квадрат =19,9, p<0.001). При этом среди всей выборки больных не отмечено корреляции уровня Клото с возрастом (r=–0,067, p=0,570), стадией ХБП (r=–0,281, p=0,06). В то же время, отмечена статистически значимая корреляция с достижением пациентом ТХПН

и началом диализа (r=–0,465, p<0,001), развитием ССО (r=–0,512, p<0,001), общей выживаемостью (r=–0,368, p=0,001). ЗАКЛЮЧЕНИЕ. По нашим данным, сывороточный уровень Клото не зависел от возраста пациентов, стадии ХБП (в выборке больных с 3–4 стадиями ХБП), однако, был четко ассоциирован с риском ССО, риском прогрессирования ХБП в ТХПН, общей выживаемостью пациентов и может рассматриваться как прогностический маркер у пациентов с додиализными стадиями ХБП.

BACKGROUND

BACKGROUND. Cardiovascular complications (CVС) are the leading cause of death in a cohort of CKD patients, including young working age people. The search for a prognostic marker that allows predicting and preventing the risk of CVС is an important not only medical but also socioeconomic task.

THE AIM OF THE STUDY

THE AIM OF THE STUDY: To determine the predictive value of baseline serum Klotho levels in assessing cardiovascular risk, risk of developing end-stage renal disease (ESRD), and overall survival among patients with stage 3-4 CKD, during an 8-year follow-up period.

PATIENTS AND METHODS

PATIENTS AND METHODS: The study included 75 patients with CKD C3-4, mean age 54+9 years. The initial serum Klotho level was divided into quartiles (1 quartile Klotho – 148-336 pg/ml; 2-3 quartile – 337-580 pg/ml; 4 quartile – 580-812 pg/ml). The overall survival of patients over a period of 8 years, the cause of death, and the achievement of ESRD, depending on the Klotho quartile, were assessed. RESULTS: During the observation period, 22 patients died, of which 12 (54.5 %) died from CVC, 7 (31.8 %) from covid infection, 3 (13.6 %) from other causes. When assessed by quartiles, patients with the 1st quartile prevailed among the deceased patients, including those from CVC: the 1st quartile was – 9 (75.0 %), the 2nd-3rd quartile -3 (25.0 %), the 4th quartile – 0 ( 0 %), (chi-square = 8.2, p=0.023). Among patients who achieved ESRD and started dialysis (n=30), patients with 1 quartile were 12 (63.2 %), 2-3 quartile -16 (43.2 %), 4 quartile – 2 (10.5 % ), (chi-square = 11.3, p = 0.01). Among the surviving patients (n=53) with CVC on the moment of end study (n=28), patients with 1 quartile were 19 (67.9 %), 2-3 quartile 9 (32.1 %), 4 quartile – 0 % (chisquare=19.9, p<0.001). At the same time, among the entire sample of patients, there was no correlation of the Klotho level with age (r=-0.067, p=0.570), CKD stage (r=-0.281, p=0.06). In the same time, there was a statistically significant correlation of Klotho level with the achievement of ESRD by the patient and the beginning of dialysis (r=-0.465, p<0.001), the development of CVC (r=-0.512, p<0.001), overall survival (r=-0.368, p=0.001).

CONCLUSION

CONCLUSION: According to our data, the serum level of Klotho did not depend on the age of patients or the stage of CKD (in the sample of patients with 3-4 stages of CKD), however, it was clearly associated with the risk of cardiovascular events, the risk of progression of CKD to ESRD, overall survival of patients and can be considered as prognostic marker in patients with pre-dialysis stages of CKD.

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