Выявление потенциальных биомаркеров дисфункции почек при артериальной гипертензии у лиц 25–45 лет
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Kovalkova N.A., Khudyakova A.D., Kashtanova E.V., et al. Detection of kidney dysfunction potential biomarkers with hypertension in the persons of 25–45 years. Therapeutic Archive. 2020; 92 (12): 19–24. DOI: 10.26442/00403660.2020.12.200436
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Материалы и методы. В исследование включены 147 человек. АГ регистрировали при артериальном давлении (АД)≥140/90 мм рт. ст., дисфункцию почек – при скорости клубочковой фильтрации (СКФ)CKD-EPI<90 мл/мин/1,73 см2. Сформированы 4 группы: 1-я – лица с АГ и СКФ<90 мл/мин/1,73 см2; 2-я – с АГ и СКФ≥90 мл/мин/1,73 см2; 3-я – с АД<140/90 мм рт. ст. и СКФ<90 мл/мин/1,73 см2; 4-я – с АД<140/90 мм рт. ст. и СКФ≥90 мл/мин/1,73 см2. Группы сопоставимы по полу, возрасту, числу респондентов. У всех лиц в сыворотке крови исследованы уровни креатинина, СДМА, уромодулина, РСБ-4, TGF-b1, ИАП-1.
Результаты. Максимальные значения СДМА определялись в 1 и 3-й группах (1,30 и 1,36 мкмоль/л). В 1-й группе выявлена ассоциация между СДМА и СКФ (r=-0,324; р=0,048). В этой же группе зарегистрированы минимальные значения уромодулина, в 4-й – максимальные (164,86 и 188,90 нг/мл; р=0,921). Уровень РСБ-4 оказался наибольшим в 1-й группе, наименьшим – в 4-й (88,64 и 80,05 мкг/мл; р=0,011). Выявлена ассоциация РСБ-4 с СДМА в 3-й группе (r=0,400; р=0,017), 4-й группе (r=0,403; р=0,018). Уровень TGF-b1 оказался в 1,5 раза выше в 1-й группе, чем в 3-й (23,16 и 15,99 мкг/мл; р=0,026), связь TGF-b1 со СКФ в 1-й группе имела обратную направленность (r=-0,452; р=0,005). Изучение аналогичных показателей ИАП-1 не обнаружило его взаимосвязей с дисфункцией почек при АГ.
Заключение. Результаты выполненного исследования позволяют рассматривать СДМА, РСБ-4, TGF-b1 в качестве потенциальных биомаркеров дисфункции почек при АГ у лиц 25–45 лет.
Ключевые слова: функция почек, артериальная гипертензия, биомаркеры.
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Aim. To assess the significance of symmetrical dimethylarginine (SDMA), uromodulin, retinol-binding protein 4 (RSB-4), transforming growth factor b1 (TGF-b1), plasminogen activator inhibitor 1 (PAI-1) as kidney dysfunction potential biomarkers persons with hypertension in persons 25–45 years old.
Materials and methods. The study included 147 people. Hypertension was recorded with blood pressure (BP)≥140/90 mm Hg, renal dysfunction – with GFRCKD-EPI<90 ml/min/1.73 cm2. Four groups were formed: 1 – individuals with hypertension and
GFR<90 ml/min/1.73 cm2; 2 – with hypertension and GFR≥90 ml/min/1.73 cm2; 3 – with BP<140/90 mm Hg and GFR<90 ml/min/1.73 cm2; 4 – with BP<140/90 mm Hg and GFR≥90 ml/min/1.73 cm2. The groups were comparable by gender, age, and number of respondents. Creatinine, SDMA, uromodulin, RSB-4, TGF-b1, PAI-1 levels were examined in all individuals in the serum.
Results. The maximum values of SDMA were determined in the 1st and 3rd groups (1.30 and 1.36 μmol/l). In the 1st group, an association was found between SDMA and GFR (r=-0.324; p=0.048). In the 1st group, the minimum values of uromodulin were recorded, in the 4th group – the maximum values (164.86 and 188.90 ng/ml; at the same time р=0.921). The level of RSB-4 was the highest in the 1st group, the lowest – in the 4th group (88.64 and 80.05 µg/ml; p=0.011). The association of RSB-4 with SDMA in the 3rd group (r=0.400; p=0.017), the 4th group (r=0.403; p=0.018) was detected. The level of TGF-b1 was 1.5 times higher in the 1st group than in the 3rd (23.16 and
15.99 µg/ml; p=0.026), the association of TGF-b1 with GFR in the 1st group had the opposite direction (r=-0.452; p=0.005). The study of similar indicators of PAI-1 did not reveal its relationship with renal dysfunction in hypertension.
Conclusion. The results of the study made it possible to consider SDMA, RSB-4, TGF-b1 as potential biomarkers of renal dysfunction in hypertension in persons 25–45 years old.
Keywords: kidney function, hypertension, biomarkers.
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1. Chazova IE, Zhernakova YuV, Oshchepkova EV, et al. Prevalence of Cardiovascular Risk Factors in Russian Population of Patients With Arterial Hypertension. Kardiologiia. 2014;10:4-12 (In Russ.) doi: 10.18565/cardio.2014.10.4-12
2. Frolov DS, Shustov SB, Barsukov AV, et al. The secondary nephropathy under arterial hypertension. Treatment and prevention. 2015;3(15):39-45 (In Russ.)
3. Singer E, Markó L, Paragas N, et al. Neutrophil gelati-nase-associated lipocalin: pathophysiology and clinical applications. Acta Physiol (Oxf). 2013;4:63-72. doi: 10.1111/apha.12054
4. Konrad M. Andrassy. Comments on "KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease". Kidney Int. 2013;3(84):622-3. doi: 10.1038/ki.2013.243
5. Kovalkova NA, Ragino YI, Hudyakovа AD, et al. Blood Pressure Levels and Prevalence of Arterial Hypertension in the Population of Residents of the Central Region of Siberia Aged 25–45 Years. Kardiologiia. 2019;59(2):32-7 (In Russ.) doi: 10.18087/cardio.2019.2.10228
6. Smirnov AV, Shilov EM, Dobronravov VA, et al. National guidelines. Chronic kidney disease: basic principles of screening, diagnosis, prevention and treatment approaches. Nephrology. 2012;16(1):89-115 (In Russ.) doi: 10.24884/1561-6274-2012-16-1-89-115
7. Schepers E, Barreto DV, Liabeuf S, et al. Symmetric Dimethylarginine as a Proinflammatory Agent in Chronic Kidney Disease. Clin J Am Soc Nephrol. 2011;6(10):2374-83. doi: 10.2215/CJN.01720211
8. Kielstein JT, Salpeter SR, Bode-Boeger SM, et al. Symmetric dimethylarginine as endogenous marker of renal function – a meta-analysis. Nephrol. Dial. Transplant. 2006;21(9):2446-51. doi: 10.1093/ndt/gfl292
9. Thongboonkerd V. Study of diabetic nephropathy in the proteomic era. Contrib Nephrol. 2011;170:172-83.
10. Fliser D, Kronenberg F, Kielstein JT, et al. Asymmetric dimethylarginine and progression of chronic kidney disease: The mild to moderate kidney disease study. J Am Soc Nephrol. 2005;16:2456-61. doi: 10.1681/ASN.2005020179
11. Smirnov AV, Hasun M, Kayukov IG, et al. Uromodulin and severity of tubulointerstitial lesions in patients with nephropathies. Nefrologiya. 2015;19(2):49-54 (In Russ.) doi: 10.26442/terarkh201890641-47
12. Steubl D, Block M, Herbst H, et al. Plasma uromodulin correlates with kidney function and identifies early stages in chronic kidney disease patients. Medicine. 2016;95:3011. doi: 10.1097/MD.0000000000003011
13. Scherberich JE, Gruber R, Nockher WA, et al. Serum uromodulin – a marker of kidney function and renal parenchymal integrity. Nephrol Dial Transplant. 2018;33(2):284-95. doi: 10.1093/ndt/gfw422
14. Bobbert T, Raila J, Schwarz F, et al. Relation between retinol, retinol-binding protein 4, transthyretin and carotid intima media thickness.
Atherosclerosis. 2010;213:549-51. doi: 10.1016/j.atherosclerosis.2010.07.063
15. Henze A, Frey SK, Raila J, et al. Alterations of retinol-binding protein 4 species in patients with different stages of chronic kidney disease and their relation to lipid parameters. Biochem Biophys Res Commun. 2010;393(1):79-83. doi: 10.1016/j.bbrc.2010.01.082
16. Frey SK, Nagl B, Henze A, et al. Isoforms of retinol binding protein 4 (RBP4) are increased in chronic diseases of the kidney but not of the liver. Lipids Health Dis. 2008;7:29. doi: 10.1186/1476-511X-7-29
17. Malgorzewicz S, Skrzypczak-Jankun E, Jankun J. Plasminogen activator inhibitor-1 in kidney pathology. Int J Mol Med. 2013;31:503-10. doi: 10.1111/jcmm
18. Scaglione R, Argano C, Chiara T, et al. Central obesity and hypertensive renal disease: association between higher levels of BMI, circulating transforming growth factor beta1 and urinary albumin excretion. Blood Press. 2003;12(5-6):269-76. doi: 10.1080/08037050310016484
19. Suthanthiran M, Gerber LM, Schwartz JE, et al. Circulating transformind growth factor-b1 levels and the risk for kidney disease in African Americans. Kidney Int. 2009;7:72-80. doi: 10.1038/ki.2009.66
Научно-исследовательский институт терапии и профилактической медицины – филиал ФГБНУ «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения РАН», Новосибирск, Россия
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N.A. Kovalkova, A.D. Khudyakova, E.V. Kashtanova, Ya.V. Polonskaya, L.V. Shcherbakova, Yu.I. Ragino
Research Institute of Internal and Preventive Medicine – branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, Novosibirsk, Russia