nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.36485/1561-6274-2019-236-100-107nefr-1774Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИ. ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL ARTICLES. EXPERIMENTAL INVESTIGATIONУровень 25-гидроксивитамина D в циркуляции ассоциирован с выраженностью фиброза почки (экспериментальное исследование)Serum 25-hydroxyvitamin D is associated with renal fi brosis (experimental study)https://orcid.org/0000-0003-1969-1959БогдановаЕ. О.BogdanovaE. O.

Богданова Евдокия Олеговна, кандидат биологических наук, Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова, Научно-исследовательский институт нефрологии, лаборатория биохимического гомеостаза

197022, Санкт-Петербург, ул. Л. Толстого, д. 17, корп. 54

Evdokia O. Bogdanova, PhD. Pavlov First Saint Petersburg State Medical University, Research Institute of Nephrology, Laboratory of Biochemical Homeostasis

197022,  St. Petersburg, L. Tolstoy st., 17, build 54

evdokia.bogdanova@gmail.comИвановаГ. Т.IvanovaG. T.

Иванова Галина Тажимовна, кандидат биологических наук, лаборатория физиологии сердечно-сосудистой и лимфатической систем, старший научный сотрудник

199034, Санкт-Петербург, наб. Макарова, д. 6

Galina T. Ivanova, PhD, senior researcher, I.P. Pavlov Institute of Physiology Russian Academy of Sciences, Laboratory of physiology of cardiovascular and lymphatic systems

199034,  St. Petersburg, Makarova Emb., 6

tazhim@list.ruhttps://orcid.org/0000-0001-7265-7392ГалкинаО. В.GalkinaO. V.

Галкина Ольга Владимировна, кандидат биологических наук, Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова, Научнои-сследовательский институт нефрологии, заведующая лабораторией биохимического гомеостаза

197022, Санкт-Петербург, ул. Л. Толстого, д. 17

Olga V. Galkina, PhD in Biology. Pavlov First Saint Petersburg State Medical University, Research Institute of Nephrology, Head of The Laboratory of Biochemical Homeostasis

197022, St. Petersburg, L. Tolstoy st., 17, build 54

ovgalkina@mail.ruЗубинаИ. М.ZubinaI. M.

Зубина Ирина Михайловна, кандидат биологических наук, Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова, Научно-исследовательский институт нефрологии, лаборатория биохимического гомеостаза

197022, Санкт-Петербург, ул. Л. Толстого, д. 17

Irina M. Zubina, PhD in Biology. Pavlov First Saint Petersburg State Medical University, Research Institute of Nephrology, Laboratory of Biochemical Homeostasis

197022, St. Petersburg, L. Tolstoy st., 17, build 54

zubina@list.ruhttps://orcid.org/0000-0002-7532-2405БересневаО. Н.BeresnevaO. N.

Береснева Ольга Николаевна, кандидат биологических наук. Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова, Научно-исследовательский институт нефрологии, лаборатория клинической физиологии почек, старший научный сотрудник

197022, Санкт-Петербург, ул. Л. Толстого, д. 17, корп. 54

Olga N. Beresneva, PhD, senior researcher. Pavlov First Saint Petersburg State Medical University, Research Institute of Nephrology, Laboratory of Clinical Physiology of the Kidney

197022, St. Petersburg, L. Tolstoy st., 17, build 54

beresnevaolga@list.ruПарастаеваМ. М.ParastaevaM. M.

Парастаева Марина Магрезовна, кандидат биологических наук. Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова, Научноисследовательский институт нефрологии, лаборатория клинической физиологии почек, старший научный сотрудник

197022, Санкт-Петербург, ул. Л. Толстого, д. 17, корп. 54

Marina M. Parastaeva, PhD, senior researcher. Pavlov First Saint Petersburg State Medical University, Research Institute of Nephrology, Laboratory of Clinical Physiology of the Kidney

197022, St. Petersburg, L. Tolstoy st., 17, build 54

parastaeva@list.ruhttps://orcid.org/0000-0003-0793-5629КаюковИ. Г.KayukovI. G.

Каюков Иван Глебович, профессор, доктор медицинских наук. Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова, Научно-исследовательский институт нефрологии, руководитель лаборатории клинической физиологии почек

197022, Санкт-Петербург, ул. Л. Толстого, д. 17, корп. 54

Ivan G. Kayukov, Prof.,  MD, PhD, DMedSci. Pavlov First Saint Petersburg State Medical University, Research Institute of Nephrology, Head of The Laboratory of Clinical Physiology of the Kidney

197022, St. Petersburg, L. Tolstoy st., 17, build 54

kvaka55@mail.ruhttps://orcid.org/0000-0002-7179-5520ДобронравовВ. А.DobronravovV. A.

Добронравов Владимир Александрович, профессор, доктор медицинских наук  Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова, заместитель директора Научно-исследовательского института нефрологии по научной работе

197022, Санкт-Петербург, ул. Л. Толстого, д. 17, корп. 54

Vladimir A. Dobronravov, Prof., MD, PhD, DMedSci. Pavlov First Saint Petersburg State Medical University, Research Institute of Nephrology, Vice-Director

197022, St. Petersburg, L. Tolstoy st., 17, build 54

dobronravov@nephrolog.ruПервый Санкт-Петербургский государственный медицинский университет им. акад. И.П. ПавловаРоссияPavlov First Saint-Petersburg State Medical UniversityRussian FederationИнститут физиологии им. И.П. Павлова РАНРоссияI.P. Pavlov Institute of Physiology Russian Academy of ScienceRussian Federation201925122019236100107Copyright © Богданова Е.О., Иванова Г.Т., Галкина О.В., Зубина И.М., Береснева О.Н., Парастаева М.М., Каюков И.Г., Добронравов В.А., 20192019Богданова Е.О., Иванова Г.Т., Галкина О.В., Зубина И.М., Береснева О.Н., Парастаева М.М., Каюков И.Г., Добронравов В.А.Bogdanova E.O., Ivanova G.T., Galkina O.V., Zubina I.M., Beresneva O.N., Parastaeva M.M., Kayukov I.G., Dobronravov V.A.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/1774ВВЕДЕНИЕ

ВВЕДЕНИЕ. Дефицит витамина D (син.: кальцитриол, D-гормон) широко распространен среди пациентов с хронической болезнью почек (ХБП), что обусловлено не только снижением биосинтеза 1,25(OH)2D3 в поврежденных канальцах нефрона, но и усилением катаболизма 1,25(OH)2D3 и 25OHD3. Уровни витамина D в сыворотке крови имеют обратную корреляцию с расчётной скоростью клубочковой фильтрации. В интервенционных исследованиях показано, что витамин D и его аналоги препятствуют прогрессированию ренального фиброза у экспериментальных животных, а также уменьшают протеинурию у пациентов с ХБП. Ренопротективные эффекты витамина D выходят далеко за рамки его классической роли в поддержании костного и минерального обмена, что является отражением его плейотропного действия. ЦЕЛЬ: исследование ассоциации между уровнем 25OH-гидроксивитамина D (25OHD) и ренальным фиброзом у спонтанно гипертензивных крыс (SHR) с начальными стадиями экспериментальной ХБП.

МАТЕРИАЛ И МЕТОДЫ

МАТЕРИАЛ И МЕТОДЫ. У нефрэктомированных (NE) и ложнооперированных (SO) крыс линии SHR (сроки наблюдения 2, 4 и 6 месяцев) и SO крыс Wistar Kyoto (срок наблюдения 2 месяца) измеряли систолическое артериальное давление (АД), протеинурию, альбуминурию, концентрации креатинина (Cr), мочевины (Ur), неорганического фосфата (Pi), 25OHD в сыворотке крови, выполняли морфологическое светооптическое исследование почки. РЕЗУЛЬТАТЫ. Экспериментальная модель соответствовала начальным стадиям ХБП (Ur: 6,64 – 13,36 ммоль/л). Значительное увеличение площади ренального фиброза у животных с NE прямо коррелировало с уровнем АД (r = 0,51, p <0,001), сывороточного Сr (r = 0,76, p <0,001), альбуминурии (r = 0,64, p <0,001) и протеинурии (r = 0,78, p <0,001) и негативно – с концентрацей 25OHD в сыворотке (r=-0,67, p<0,001), при множественном регрессионном анализе достоверная корреляция между площадью фиброза и уровнем 25OHD сохранялась (β= –0,28, p=0,012). Кроме того, для 25OHD были получены наиболее высокие значения площади под кривой (AUC = 0,95) при выявлении интерстициального фиброза более 10 %.

ЗАКЛЮЧЕНИЕ

ЗАКЛЮЧЕНИЕ. Снижение концентрации 25ОНD в сыворотке крови на начальных стадиях экспериментальной ХБП и артериальной гипертензии независимо ассоциировано с развитием почечного фиброза.

INTRODUCTION

INTRODUCTION. Vitamin D deficiency is commonly observed in patients with chronic kidney disease (CKD) due to decreased biosynthesis of 1,25(OH)2D3 in damaged renal tubules and increased catabolism of 1,25(OH)2D3 and 25OHD3. There is a growing evidence that vitamin D deficiency may contribute to impaired kidney function. Interventional studies have shown that vitamin D and its analogs attenuate the progression of renal fibrosis in experiment, and reduce proteinuria in patients with CKD. The renoprotective effects of vitamin D go far beyond its classical role in maintaining bone and mineral metabolism, which is a result of its pleiotropic action. THE AIM: to investigate the association between 25OH-hydroxyvitamin D (25OHD) level and renal fibrosis in spontaneously hypertensive rats (SHR) with early stages of experimental CKD.

MATERIAL AND METHODS

MATERIAL AND METHODS. Systolic blood pressure (BP), proteinuria, albuminuria, creatinine (Cr), urea (Ur), inorganic phosphate (Pi), 25OHD in serum were measured in nephrectomized (NE) and sham operated (SO) spontaneously hypertensive rats SHR (follow-up period 2, 4 and 6 months) and SO Wistar Kyoto rats (follow-up period 2 months), morphological light-optical study of kidney tissue was performed.

RESULTS

RESULTS. The experimental model corresponded to the initial stages of CKD (Ur: 6.64 – 13.36 mmol/L). A significant increase in the area of renal fibrosis in animals with NE correlated with an increase in blood pressure (r = 0.51, p <0.001), serum Cr (r = 0.76, p <0.001), and albuminuria (r = 0.64, p <0.001) and proteinuria (r = 0.78, p <0.001) and a decrease in the concentration of 25OHD in serum (r = -0.67, p <0.001). In multiple regression analyzes, a reliable association of fibrosis with 25OHD was maintained (β = -0.28, p = 0.012). In addition, in ROC-analysis the largest value of the area under the curve was obtained for 25OHD (AUC = 0.95) to detect interstitial fibrosis more than 10 %.

CONCLUSION

CONCLUSION. 25OHD depression at the initial stages of experimental CKD and hypertension is independently associated with the development of renal fibrosis.

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