Циркулирующие микроРНК как потенциальные биомаркеры хронической болезни почек

Айтбаев К.А., Муркамилов И.Т., Фомин В.В. Циркулирующие микроРНК как потенциальные биомаркеры хронической болезни почек. Терапевтический архив. 2019; 91 (6): 131–136. DOI: 10.26442/00403660.2019.06.000046

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Aitbaev K.A., Murkamilov I.T., Fomin V.V. Circulating microRNAs as potential biomarkers of chronic kidney disease. Therapeutic Archive. 2019; 91 (6): 131–136.
DOI: 10.26442/00403660.2019.06.000046

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Аннотация

Хроническая болезнь почек (ХБП) – наднозологическое понятие, отражающее прогрессирующий характер хронических заболеваний почек, в основе которых лежат механизмы формирования нефросклероза. Диагностика ХБП на самых ранних стадиях имеет большое значение, так как позволяет своевременно начать лечение и замедлить прогрессирование почечной дисфункции и развитие сердечно-сосудистых осложнений ХБП. Однако имеющиеся сегодня методы диагностики нарушений почечной функции, в том числе определение клиренса эндогенного креатинина, способны выявлять ренальную дисфункцию слишком поздно, когда около 40–50% почечной паренхимы уже становятся обратимо или необратимо поврежденными. В связи с этим ведется активный поиск новых, более чувствительных и специфических биомаркеров для ранней диагностики ХБП. Недавние исследования на клеточных и животных моделях ХБП продемонстрировали важную роль микроРНК – нового класса посттранскрипционных регуляторов экспрессии генов – в физиологии и патофизиологии почек. В частности, показано, что их профиль экспрессии в крови или моче может отражать изменения в клетках, участвующих в конкретном патологическом процессе, поскольку эти клетки могут выделять определенную популяцию микроРНК, например через секрецию микроРНК-содержащих экзосом. Это дало основание рассматривать повышение или снижение экспрессии отдельных микроРНК в почечной ткани или биологических жидкостях (в том числе в моче) в качестве новых биомаркеров для диагностики и мониторирования ХБП. В настоящем обзоре представлены результаты последних экспериментальных и клинических исследований по обсуждаемой проблеме.

Ключевые слова: хроническая болезнь почек, биомаркер, микроРНК.

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Chronic kidney disease (CKD) is a supra-nosological term that reflects the progressive nature of chronic kidney diseases, which are based on the mechanisms of nephrosclerosis. Diagnosis of CKD at the earliest stages is of great importance, because it allows, by using therapeutic agents, to slow the progression of renal dysfunction and the development of cardiovascular complications. However, the currently available methods for diagnosing renal function impairment, including the determination of endogenous creatinine clearance, can detect renal dysfunction too late, when around 40–50% of the renal parenchyma is already reversibly or irreversibly damaged. In this regard, there is an active search for new, more sensitive and specific biomarkers for early diagnosis of CKD. Recent studies in cellular and animal models of CKD have demonstrated the important role of microRNA, a new class of posttranscriptional regulators of gene expression, in physiology and pathophysiology of kidneys. In particular, it has been shown that their expression profile in blood or urine can reflect changes in cells involved in a particular pathological process, since these cells can secrete a specific population of microRNAs, for example, through secretion of microRNA-containing exosomes. This gave grounds for considering increased or decreased expression of individual microRNAs in renal tissue or biological fluids (including urine) as new biomarkers for the diagnosis and monitoring of CKD. This review presents the results of recent experimental and clinical studies on these issues.

Key words: chronic kidney disease, biomarker, microRNA.

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1. Codreanu I, Perico N, Sharm SK, et al. Prevention programmes of progressive renal disease in developing nations. Nephrology. 2006;11:321-8. doi: 10.1111/j.1440-1797.2006.00587.x
2. Chadban S, Briganti EM, Kerr PG, et al. Prevalence of kidney damage in Australian adults: the AusDiab kidney study. J Am Soc Nephrol. 2003;14 Suppl 2:S131-S138. PMID: 12819318
3. Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States. JAMA J Am Med Assoc. 2007;298:2038-47. doi: 10.1001/jama.298.17.2038
4. Hallan SI, Coresh J, Astor BC, et al. International comparison of the relationship of chronic kidney disease prevalence and ESRD risk. J Am Soc Nephrol. 2006;17:2275-84. doi: 10.1681/ASN.2005121273
5. Zhang L, Zhang P, Wang F, et al. Prevalence and factors associated with CKD: a population study fr om Beijing. Am J Kidney Dis. 2008;51:373-84. doi: 10.1053/j.ajkd.2007.11.009
6. Levey AS, Atkins R, Coresh J, et al. Chronic kidney disease as a global public health problem: approaches and initiatives – a position statement from Kidney Disease Improving Global Outcomes. Kidney Int. 2007;72:247-59. doi: 10.1038/sj.ki.5002343
7. World Health Organization. The Global Burden of Disease: 2004 Update. Geneva: World Health Organization, 2008.
8. Khan Z, Pandey M. Role of kidney biomarkers of chronic kidney disease: An update. Saudi J Biol Sci. 2014;21:294-9. doi: 10.1016/j.sjbs.2014.07.003
9. Viau A, Karoui KE, Laouari D, et al. Lipocalin 2 is essential for chronic kidney disease in mice and human. J Clin Investig. 2010;120:4065-76. doi: 10.1172/JCI42004
10. Hostetter TH. Progression of renal disease and renal hypertrophy. Annu Rev Physiol. 1995;57:263-78. doi: 10.1146/annurev.ph.57.030195.001403
11. Kliem V, Johnson RJ, Alpers CE, et al. Mechanisms involved in the pathogenesis of tubulointerstitial fibrosis in 5/6-nephrectomized rats. Kidney Int. 1996;49:666-78. PMID: 8648907
12. Pillebout E, Weitzman JB, Burtin M, et al. JunD protects against chronic kidney disease by regulating paracrine mitogens. J Clin Investig. 2003;112:843-52. doi: 10.1172/JCI200317647
13. Steubl D, Block M, Herbst V, et al. Plasma uromodulin correlates with kidney function and identifies early stages in chronic kidney disease patients. Medicine. 2016;95:e3011. doi: 10.1097/MD.0000000000003011
14. Wasung ME, Chawla LS, Madero M. Biomarkers of renal function, which and when? Clin Chim Acta. 2015;438:350-7. doi: 10.1016/j.cca.2014.08.039
15. Fink HA, Ishani A, Taylor BC, et al. Chronic Kidney Disease Stages 1–3: Screening, Monitoring, and Treatment; Agency for Healthcare Research and Quality. Rockville, MD, USA, 2012. PMID: 22439155
16. Khurana R, Ranches G, Schafferer S, et al. Identification of urinary exosomal noncoding RNAs as novel biomarkers in chronic kidney disease. RNA. 2017;23:142-52. doi: 10.1261/rna.058834.116
17. Liu Y. Cellular and molecular mechanisms of renal fibrosis. Nat Rev Nephrol. 2011;7:684-96. doi: 10.1038/nrneph.2011.149
18. Mayer G. Capillary rarefaction, hypoxia, VEGF and angiogenesis in chronic renal disease. Nephrol Dial Transplant. 2011;26:1132-7. doi: 10.1093/ndt/gfq832
19. Quaggin SE, Kreidberg JA. Development of the renal glomerulus: Good neighbours and good fences. Development. 2008;135:609-20. doi: 10.1242/dev.001081
20. Biragova M.S., Gracheva S.A., Martynov S.A. Compromised calcium and phosphorus metabolism in patients with diabetes mellitus and chronic kidney disease. Sakharnyi diabet = Diabetes mellitus. 2012;(4):74-80. doi: 10.14341/2072-0351-5542 (In Russ.)
21. Barreto FC, Barreto DV, Liabeuf S, et al. Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients. Clin J Am Soc Nephrol. 2009;4:1551-8. doi: 10.2215/CJN.03980609
22. Smirnov AV, Karunnaya AV, Zarayski MI, et al. Urinary microRNA-21 expression in nephropathies. Nefrologiya = Nephrology (Saint-Petersburg). 2014;18(6):59-63 (In Russ.)
23. Kamyshova ES, Bobkova IN. MicroRNAs in chronic glomerulonephritis: Promising biomarkers for diagnosis and prognosis estimation. Therapeutic Archive. 2017;89(6):89-96 (In Russ.) doi: 10.17116/terarkh201789689-96
24. Kamyshova ES, Bobkova IN, Kutyrina IM. New insights on microRNAs in diabetic nephropathy: potential biomarkers for diagnosis and therapeutic targets. Sakharnyi diabet = Diabetes mellitus. 2017;20(1):42-50 (In Russ.) doi: 10.14341/DM8237
25. Wang F, Chen C, Wang D. Circulating microRNAs in cardiovascular disease: from biomarkers to therapeutic targets. Front Med. 2014;8:404-18. doi: 10.1007/s11684-014-0379-2
26. Valadi H, Ekström K, Bossios A, et al. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9:654-9. doi: 10.1038/ncb1596
27. Chim SS, Shing TK, Hung EC, et al. Detection and characterization of placental microRNAs in maternal plasma. Clin Chem. 2008;54:482-90. doi: 10.1373/clinchem.2007.097972
28. Van Craenenbroeck AH, Ledeganck KJ, van Ackeren K, et al. Plasma levels of microRNA in chronic kidney disease: patterns in acute and chronic exercise. Am J Physiol Heart Circ Physiol. 2015;309:H2008-H2016. doi: 10.1152/ajpheart.00346.2015
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Авторы

К.А. Айтбаев1, И.Т. Муркамилов2,3, В.В. Фомин4

1 Научно-исследовательский институт молекулярной биологии и медицины при Национальном центре кардиологии и терапии Минздрава Кыргызской Республики, Бишкек, Кыргызстан;
2 Кыргызская государственная медицинская академия им. И.К. Ахунбаева, Бишкек, Кыргызстан;
3 Кыргызско-Российский Славянский университет им. первого Президента России Б.Н. Ельцина, Бишкек, Кыргызстан;
4 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия

________________________________________________

K.A. Aitbaev1, I.T. Murkamilov2,3, V.V. Fomin4

1 Scientific and Research Institute of Molecular Biology and Medicine, Bishkek, Kyrgyzstan;
2 Akhunbaev Kyrgyz State Medical Academy, Bishkek, Kyrgyzstan;
3 Kyrgyz Russian Slavic University named after the First President of Russia B.N. Yeltsin, Bishkek, Kyrgyzstan;
4 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia

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