<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article 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" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Terapevticheskii arkhiv</journal-id><journal-title-group><journal-title xml:lang="en">Terapevticheskii arkhiv</journal-title><trans-title-group xml:lang="ru"><trans-title>Терапевтический архив</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0040-3660</issn><issn publication-format="electronic">2309-5342</issn><publisher><publisher-name xml:lang="en">LLC Obyedinennaya Redaktsiya</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">34981</article-id><article-id pub-id-type="doi">10.26442/00403660.2020.06.000670</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Original articles</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Оригинальные статьи</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Low serum Klotho level as a predictor of calcification of the heart and blood vessels in patients with CKD stages 2–5D</article-title><trans-title-group xml:lang="ru"><trans-title>Низкий сывороточный уровень Klotho как предиктор кальцификации сердца и сосудов у больных хронической болезнью почек 2–5D стадий</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5599-0350</contrib-id><name-alternatives><name xml:lang="en"><surname>Milovanova</surname><given-names>Ludmila Yu.</given-names></name><name xml:lang="ru"><surname>Милованова</surname><given-names>Людмила Юрьевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="ru"><p>д.м.н., проф. каф. внутренних, профессиональных болезней и ревматологии</p></bio><email>Ludm.milovanova@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1166-7308</contrib-id><name-alternatives><name xml:lang="en"><surname>Lysenko (Kozlovskaya)</surname><given-names>Lidia V.</given-names></name><name xml:lang="ru"><surname>Лысенко (Козловская)</surname><given-names>Лидия Владимировна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="ru"><p>д.м.н., проф. каф. внутренних, профессиональных болезней и ревматологии</p></bio><email>Ludm.milovanova@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2687-6161</contrib-id><name-alternatives><name xml:lang="en"><surname>Milovanova</surname><given-names>Svetlana Yu.</given-names></name><name xml:lang="ru"><surname>Милованова</surname><given-names>Светлана Юрьевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="ru"><p>д.м.н., проф. каф. внутренних, профессиональных болезней и ревматологии.</p></bio><email>Ludm.milovanova@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7363-6195</contrib-id><name-alternatives><name xml:lang="en"><surname>Taranova</surname><given-names>Marina V.</given-names></name><name xml:lang="ru"><surname>Таранова</surname><given-names>Марина Владимировна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="ru"><p>к.м.н., доц. каф. внутренних, профессиональных болезней и ревматологии</p></bio><email>Ludm.milovanova@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2389-3820</contrib-id><name-alternatives><name xml:lang="en"><surname>Kozlov</surname><given-names>Vasiliy V.</given-names></name><name xml:lang="ru"><surname>Козлов</surname><given-names>Василий Владимирович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="ru"><p>доц. каф. общественного здоровья и организации здравоохранения</p></bio><email>Ludm.milovanova@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2987-7995</contrib-id><name-alternatives><name xml:lang="en"><surname>Reshetnikov</surname><given-names>Vladimir A.</given-names></name><name xml:lang="ru"><surname>Решетников</surname><given-names>Владимир Анатольевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="ru"><p>д.м.н., проф. каф. общественного здоровья и организации здравоохранения</p></bio><email>Ludm.milovanova@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5923-1837</contrib-id><name-alternatives><name xml:lang="en"><surname>Lebedeva</surname><given-names>Marina V.</given-names></name><name xml:lang="ru"><surname>Лебедева</surname><given-names>Марина Валерьевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="ru"><p>к.м.н., доц. каф. внутренних, профессиональных болезней и ревматологии</p></bio><email>Ludm.milovanova@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9951-126X</contrib-id><name-alternatives><name xml:lang="en"><surname>Androsova</surname><given-names>Tatyana V.</given-names></name><name xml:lang="ru"><surname>Андросова</surname><given-names>Татьяна Витальевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="ru"><p>к.м.н., доц. каф. внутренних, профессиональных болезней и ревматологии</p></bio><email>Ludm.milovanova@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8020-7041</contrib-id><name-alternatives><name xml:lang="en"><surname>Zubacheva</surname><given-names>Daria O.</given-names></name><name xml:lang="ru"><surname>Зубачева</surname><given-names>Дарья Олеговна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="ru"><p>ординатор 1-го года обучения каф. внутренних, профессиональных болезней и ревматологии</p></bio><email>Ludm.milovanova@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2128-8560</contrib-id><name-alternatives><name xml:lang="en"><surname>Chebotareva</surname><given-names>Natalia V.</given-names></name><name xml:lang="ru"><surname>Чеботарева</surname><given-names>Наталья Викторовна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="ru"><p>д.м.н., проф. каф. внутренних, профессиональных болезней и ревматологии</p></bio><email>Ludm.milovanova@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Sechenov First Moscow State Medical University (Sechenov University)</institution></aff><aff><institution xml:lang="ru">ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет)</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2020-07-09" publication-format="electronic"><day>09</day><month>07</month><year>2020</year></pub-date><volume>92</volume><issue>6</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>37</fpage><lpage>45</lpage><history><date date-type="received" iso-8601-date="2020-07-08"><day>08</day><month>07</month><year>2020</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2020, Consilium Medicum</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2020, ООО "Консилиум Медикум"</copyright-statement><copyright-year>2020</copyright-year><copyright-holder xml:lang="en">Consilium Medicum</copyright-holder><copyright-holder xml:lang="ru">ООО "Консилиум Медикум"</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc-sa/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://ter-arkhiv.ru/0040-3660/article/view/34981">https://ter-arkhiv.ru/0040-3660/article/view/34981</self-uri><abstract xml:lang="en"><p> </p> <p>Cardiovascular calcification (CVC) makes a significant contribution to the manifestation of cardiovascular complications in patients with chronic kidney disease. Early CVC markers are currently being actively studied to optimize cardio-renoprotective strategies. We performed a prospective comparative analysis of the following factors: FGF-23, a-Klotho, sclecrostin, phosphate, parathyroid hormone, the estimated glomerular filtration rate (eGFR), central systolic pressure as an independent determinant of CVC.</p> <p><bold>Materials and methods. </bold>The study included 131 patients with chronic kidney disease 2–5D st. Serum levels of FGF-23, Klotho, and sclerostin were evaluated using the ELISA method. Vascular augmentation (stiffness) indices, central arterial pressure (using the SphygmoCor device), calcification of heart valves and the degree of aortic calcification (aortic radiography) were also investigated. The observation period was 2 years.</p> <p><bold>Results. </bold>According to the Spearman correlation analysis, the percent of calcification increase and the change in Klotho level are most related. According to ROC analysis, a decrease in serum levels of Klotho by 50 units or more is a significant predictor of an increase in aortic calcification of 50% or more with a sensitivity of 86% and a specificity of 77%. Using logistic regression analysis, it was found that a serum Klotho level &lt;632 pg/L predicts an eGFR below a median level of 48 ml/min/1.73 m<sup>2</sup> with a sensitivity of 85.5% and a specificity of 78.5%. Wherein OR 17.477 (CI 95% 8.046–37.962; <italic>p</italic>&lt;0.001).</p> <p><bold>Conclusion. </bold>The factor most associated with CVC is Klotho. Decreased serum level of Klotho is a predictor of aortic calcification. In addition, the initial serum level of Klotho is a predictor of eGFR after 2 years.</p></abstract><trans-abstract xml:lang="ru"><p>Кардиоваскулярная кальцификация (КВК) вносит существенный вклад в проявление сердечно-сосудистых осложнений у больных хронической болезнью почек (ХБП).</p> <p><bold>Цель. </bold>Изучить ранние маркеры КВК с целью оптимизации кардиоренопротективной стратегии. Проведен проспективный сравнительный анализ следующих факторов: фактора роста фибробластов 23, a-Klotho, склеростина, фосфата, паратиреоидного гормона, расчетной скорости клубочковой фильтрации (рСКФ), центрального систолического давления – как независимых детерминант КВК.</p> <p><bold>Материалы и методы. </bold>В исследование включен 131 пациент с ХБП 2–5D стадий. Сывороточные уровни FGF-23, Klotho и склеростина оценивались с помощью ELISA-метода. Исследованы также индексы аугментации (жесткости) сосудов, центральное артериальное давление (с помощью прибора SphygmoCor), кальцификация клапанов сердца и степень кальциноза аорты (рентгенография аорты). Период наблюдения составил 2 года.</p> <p><bold>Результаты. </bold>Согласно корреляционному анализу Спирмена в наибольшей степени связаны процент повышения кальцификации и изменение уровня Klotho. Согласно ROC-анализу снижение сывороточного уровня Klotho на 50 ЕД и более является существенным предиктором увеличения кальцификации аорты на 50% и более с чувствительностью 86% и специфичностью 77%. С помощью логистического регрессионного анализа выявлено, что сывороточный уровень Klotho ниже 632 пг/л предсказывает рСКФ ниже медианного уровня 48 мл/мин/1,73 м<sup>2</sup> с чувствительностью 85,5% и специфичностью 78,5%. При этом OШ 17,477 (ДИ 95% 8,046–37,962; <italic>p</italic>&lt;0,001).</p> <p><bold>Заключение.</bold> Фактором, наиболее ассоциированным с КВК, является Klotho. Снижение сывороточного уровня Klotho – предиктор аортальной кальцификации. Кроме того, исходный сывороточный уровень Klotho является предиктором рСКФ через 2 года.</p></trans-abstract><kwd-group xml:lang="en"><kwd>chronic kidney disease</kwd><kwd>fibroblast growth factor 23</kwd><kwd>Klotho</kwd><kwd>sclerostin</kwd><kwd>cardiovascular calcification</kwd><kwd>heart remodeling</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>хроническая болезнь почек</kwd><kwd>фактор роста фибробластов 23</kwd><kwd>Klotho</kwd><kwd>склеростин</kwd><kwd>кардиоваскулярная кальцификация</kwd><kwd>ремоделирование сердца</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Couser WG, Remuzzi G, Mendis S, et al. The contribution of chronic kidney disease to the global burden of major noncommunicable diseases. Kidney Int. 2011;80(12):1258-70. doi: 10.1038/ki.2011.368. Epub 2011 Oct 12.</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296-305. doi: 10.1056/NEJMoa041031</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Kumar S, Bogle R, Banerjee D. Why do young people with chronic kidney disease die early? World J Nephrol. 2014;3(4):143-55. doi: 10.5527/wjn.v3.i4.143</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Garland JS, Holden RM, Groome PA, et al. Prevalence and associations of coronary artery calcification in patients with stages 3 to 5 CKD without cardiovascular disease. Am J Kidney Dis. 2008;52(5):849-58. doi: 10.1053/j.ajkd.2008.04.012. Epub 2008 Jun 17.</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Memmos E, Sarafidis P, Pateinakis P, et al. Soluble Klotho is associated with mortality and cardiovascular events in hemodialysis. BMC Nephrol. 2019;20:217. doi: 10.1186/s12882-019</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Lu X, Hu MC. Klotho/FGF23 Axis in Chronic Kidney Disease and Cardiovascular Disease. Kidney Dis. 2016;17:1-9.</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Milovanova LY, Fomin VV, Lysenko (Kozlovskaya) LV, et al. Disorders in the system of mineral and bone metabolism regulators – FGF-23, Klotho and Sclerostin – in chronic kidney disease: clinical significance and possibilities for correction. In Rath T, editor. Chronic Kidney Disease. From Pathophysiology to Clinical Improvements. London: IntechOpen Limited; 2018; p. 43-60. doi: 10.5772/intechopen.69298</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Isakova T, Wahl P, Vargas GS, et al. Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int. 2011;79:1370-8. doi: 10.1038/ki.2011.47. Epub 2011 Mar 9</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Milovanova L, Kozlovskaya L, Markina M, et al. Morphogenetic proteins – fibroblast growth factor-23 (FGF-23) and Klotho in serum of patients with chronic kidney disease, as the markers of cardiovascular risk. Clin Med. 2016;12:34-40.</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Gutiérrez OM, Januzzi JL, Isakova T, et al. Fibroblast growth factor-23 and left ventricular hypertrophy in chronic kidney disease. Circulation. 2009;119(19):2545-52. doi: 10.1161/CIRCULATIONAHA.108.844506</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Sharaf UA, Din El, Salem MM, Abdulazim DO. Is Fibroblast growth factor 23 the leading cause of increased mortality among chronic kidney disease patients? A narrative review. J Adv Res. 2017;8(3):271-8. doi: 10.1016/j.jare.2017.02.003</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Donate-Correa J, Martín-Núñez E, Mora-Fernández C, et al. Klotho in cardiovascular disease: Current and future perspectives. World J Biol Chem. 2015;6(4):351-7. doi: 10.4331/wjbc.v6.i4.351</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Милованова Л.Ю., Мухин Н.А., Козловская Л.В. и др. Снижение сывороточного уровня морфогенетического белка Klotho у больных хронической болезнью почек: клиническое значение. Вестн. РАМН. 2016;71:288-96 [Milovanova LY, Mukhin NA, Kozlovskaya LV, et al. Decreased serum levels of klotho protein in chronic kidney disease patients: Clinical importance. Vestn. Ross. Akad. Meditsinskikh Nauk. 2016;71:288-96 (In Russ.)]. doi: 10.15690/vramn581</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Kuro-o M, Matsumura Y, Aizawa H, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997;390:45-51. doi: 10.1038/36285</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Urakawa I, Yamazaki Y, Shimada T, et al. Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature. 2006;444:770-4. doi: 10.1038/nature05315</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Saito Y, Yamagishi T, Nakamura T, et al. Klotho protein protects against endothelial dysfunction. Biochem Biophys Res Commun. 1998;248:324-9. doi: 10.1006/bbrc.1998.8943</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Kusaba T, Okigaki M, Matui A, et al. Klotho is associated with VEGF receptor-2 and the transient receptor potential canonical-1 Ca2+ channel to maintain endothelial integrity. Proc Natl Acad Sci USA. 2010;107:19308-13. doi: 10.1073/pnas.1008544107</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Semba RD, Cappola AR, Sun K, et al. Plasma klotho and mortality risk in older community-dwelling adults. J Gerontol A Biol Sci Med Sci. 2011;66:794-800. doi: 10.1093/gerona/glr058</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Cejka D, Herberth J, Branscum AJ, et al. Sclerostin and Dickkopf-1 in renal osteodystrophy. Clin J Am Soc Nephrol. 2011;6:877-82. doi: 10.2215/CJN.06550810</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>Bruzzese A, Lacquaniti A, Cernaro V, et al. Sclerostin levels in uremic patients: a link between bone and vascular disease. J Renal Failure. 2016;38(5):123-9. doi: 10.3109/0886022X.2016.1160207</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Kanbay M, Solak Y, Siriopol D, et al. A. Sclerostin, cardiovascular disease and mortality: a systematic review and meta-analysis. Int Urol Nephrol. 2016;48(12):2029-42. doi: 10.1007/s11255-016-1387-8</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2013;3 (Suppl. 1). http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_2012_CKD_GL.pdf</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Cheng H-M, Chuang S-Y, Sung S-H, et al. Derivation and validation of diagnostic thresholds for central blood pressure measurements based on long-term cardiovascular risks. J Am Coll Cardiol. 2013;92(19):1780-87. doi: 10.1016/j.jacc.2013.06.029</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Ermolenko VM, Volgina GV, Dobronravov VA, et al. National recommendations on mineral and bone disorders in chronic kidney disease. Russian Dialysis Society (May 2010). Nephrologia I Dialis. 2011;13(1):33-51.</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Mancia G, Fagard R, et al. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34:2159-219. doi: 10.1097/01.hjh.0000431740.32696.cc</mixed-citation></ref><ref id="B26"><label>26.</label><mixed-citation>Heine GH, Nangaku M, Fliser D. Calcium and phosphate impact cardiovascular risk. Eur Heart J. 2013;34:1112-21. doi: 10.1093/eurheartj/ehs353</mixed-citation></ref><ref id="B27"><label>27.</label><mixed-citation>Milovanova L, Milovanov Y, Plotnikova A. Phosphorus and calcium metabolism disorders associated with chronic kidney disease stage III-IV (Systematic Review and Meta-Analysis). In Sahay M, editor. Chronic Kidney Disease and Renal Transplantation. London: IntechOpen Limited; 2012; p. 95-118. doi: 10.5772/25689</mixed-citation></ref><ref id="B28"><label>28.</label><mixed-citation>Chertow GM, Block GA, Correa-Rotter R, et al. EVOLVE Trial Investigators: Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med. 2012;367:2482-94. doi: 10.1056/NEJMoa1205624</mixed-citation></ref><ref id="B29"><label>29.</label><mixed-citation>Block GA, Wheeler DC, Persky MS, et al Effects of Phosphate Binders in Moderate CKD. J Am Soc Nephrol. 2012;23(8):1407-15. doi: 10.1681/ASN.2012030223</mixed-citation></ref><ref id="B30"><label>30.</label><mixed-citation>Thadhani R, Appelbaum E, Pritchett Y, et al. Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. JAMA. 2012;307(7):674-84. doi: 10.1001/jama.2012.120</mixed-citation></ref><ref id="B31"><label>31.</label><mixed-citation>Jimbo R, Kawakami-Mori F, Mu S, et al. Fibroblast growth factor 23 accelerates phosphate-induced vascular calcification in the absence of Klotho deficiency. Kidney Int. 2014;85(5):1103-11. doi: 10.1038/ki.2013.332</mixed-citation></ref><ref id="B32"><label>32.</label><mixed-citation>Zhou L, Li Y, Zhou D, et al. Loss of Klotho contributes to kidney injury by derepression of Wnt/β-catenin signaling. J Am Soc Nephrol. 2013;24:771-85. doi: 10.1681/ASN.2012080865</mixed-citation></ref><ref id="B33"><label>33.</label><mixed-citation>Maekawa Y, Ishikawa K, Yasuda O, et al. Klotho suppresses TNF-alpha-induced expression of adhesion molecules in the endothelium and attenuates NF-kappaB activation. Endocrine. 2009;35:341-6. doi: 10.1007/s12020-009-9181-3</mixed-citation></ref><ref id="B34"><label>34.</label><mixed-citation>Munoz Mendoza J, Isakova T, Ricardo AC, et al. Fibroblast growth factor 23 and Inflammation in CKD. Clin J Am Soc Nephrol. 2012;7(7):1155-62. doi: 10.2215/CJN.13281211</mixed-citation></ref><ref id="B35"><label>35.</label><mixed-citation>NasrAllah MM, El-Shehaby AR, Osman NA, et al. The Association between Fibroblast growth factor-23 and vascular calcification is mitigated by inflammation markers. Nephron Extra. 2013;3(1):106-12.</mixed-citation></ref><ref id="B36"><label>36.</label><mixed-citation>Milovanova LY, Kozlovskaya LV, Milovanova SY, et al. Associations of fibroblast growth factor 23, soluble Klotho, troponin i in CKD patients. Int Res J. 2016;9(51):65-9.</mixed-citation></ref><ref id="B37"><label>37.</label><mixed-citation>Claes KJ, Viaene L, Heye S, et al. Sclerostin: Another vascular calcification inhibitor? J Clin Endocrinol Metab. 2013;98(8):3221-8. doi: 10.1210/jc.2013-1521</mixed-citation></ref><ref id="B38"><label>38.</label><mixed-citation>Register TC, Hruska KA, Divers J, et al. Sclerostin is positively associated with bone mineral density in men and women and negatively associated with carotid calcified atherosclerotic plaque in men from the African American-Diabetes Heart Study. J Clin Endocrinol Metab. 2014;99(1):315-21. doi: 10.1210/jc.2013-3168</mixed-citation></ref><ref id="B39"><label>39.</label><mixed-citation>Monroe DG, McGee-Lawrence ME, Oursler MJ, et al. Update on Wnt signaling in bone cell biology and bone disease. Gene. 2012;492(1):1-18. doi: 10.1016/j.gene.2011.10.044</mixed-citation></ref></ref-list></back></article>
