cardiovascularКардиоваскулярная терапия и профилактикаCardiovascular Therapy and Prevention1728-88002619-0125«SILICEA-POLIGRAF» LLC10.15829/1728-8800-2019-3-88-93cardiovascular-819Research ArticleМНЕНИЕ ПО ПРОБЛЕМЕOPINION ON A PROBLEMСпецифические факторы риска развития цереброваскулярных нарушений у пациентов хронической болезнью почек в додиализный периодSpecific risk factors for cerebrovascular disorders in patients with chronic kidney disease in the pre-dialysis periodhttps://orcid.org/0000-0003-0169-3956ХрулёвА. Е.KhrulevA. E.

Хрулёв Алексей Евгеньевич — кандидат медицинских наук, доцент кафедры неврологии, нейрохирургии и медицинской генетики

Нижний Новгород

alexey_khrulev@mail.ruhttps://orcid.org/0000-0001-7973-3482НикитинаА. А.NikitinaA. A.

Никитина Анастасия Александровна — аспирант кафедры неврологии, нейрохирургии и медицинской генетики

Нижний Новгород

asia333@yandex.ruhttps://orcid.org/0000-0003-3311-4437ХрулёваН. С.KhrulevaN. S.

Хрулёва Наталья Сергеевна — кандидат медицинских наук, ассистент кафедры госпитальной терапии им. В. Г. Вогралика

Нижний Новгород

natalynnov_82@mail.ruФГБОУ ВО «Приволжский исследовательский медицинский университет» Министерства здравоохранения Российской ФедерацииPrivolzhsky Research Medical University2019130620191838893Copyright © Хрулёв А.Е., Никитина А.А., Хрулёва Н.С., 20192019Хрулёв А.Е., Никитина А.А., Хрулёва Н.С.Khrulev A.E., Nikitina A.A., Khruleva N.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://cardiovascular.elpub.ru/jour/article/view/819

Церебральные сосудистые расстройства являются одной из ведущих причин инвалидизации и смертности пациентов с хронической болезнью почек (ХБП). В статье представлена имеющаяся к настоящему времени информация о факторах риска (ФР) развития цереброваскулярных нарушений у пациентов с ХБП в додиализный период. Выделены две группы ФР: традиционные и нетрадиционные (специфические). Традиционные ФР, к которым относят артериальную гипертензию, сахарный диабет и гиперхолестеринемию, независимо воздействуют на сосудистое церебральное русло и усугубляются на фоне ХБП. Специфические ФР связаны с особенностями патогенеза ХБП. К ним относят повышение уровней в крови гомоцистеина, β2-микроглобулина, нарушения фосфорно-кальциевого обмена, накопление уремических токсинов и токсинов кишечных бактерий, анемия и другие факторы. В представленном обзоре особое внимание уделено специфическим ФР, подробно описаны возможные патогенетические механизмы развития цереброваскулярных нарушений у пациентов с ХБП в додиализный период. Своевременное выявление факторов церебрального риска и у этой категории больных может способствовать улучшению ранней диагностики и профилактики церебральных сосудистых расстройств, оптимизации терапии пациентов с ХБП.

Cerebral vascular disorders are one of the leading causes of disability and mortality in patients with chronic kidney disease (CKD). The article presents the currently available data on risk factors (RF) for the development of cerebrovascular disorders in pre-dialysis patients with CKD. Two groups of RF are identified: traditional and non-traditional (specific). Traditional RF, which include arterial hypertension, diabetes mellitus and hypercholesterolemia, independently affect the cerebral vascular bed and get worse against the background of CKD. Specific RF is associated with features of the CKD pathogenesis. It includes increased blood levels of homocysteine, β2-microglobulin, impaired calcium-phosphorus metabolism, accumulation of uremic toxins and toxins of intestinal bacteria, anemia and other factors. In the present review, special attention is paid to specific RF and pathogenetic mechanisms of the development of cerebrovascular disorders in predialysis patients with CKD. Timely detection of cerebral risk factors may lead to the improvement of early diagnosis and prevention of cerebral vascular disorders, optimization of therapy for patients with CKD.

хроническая болезнь почекцереброваскулярные нарушенияинсультфакторы рискагипергомоцистеинемиявторичный амилоидозуремические токсинытоксины кишечных бактерийнарушение фосфорно-кальциевого обменаchronic kidney diseasecerebrovascular disordersstrokerisk factorshyperhomocysteinemiasecondary amyloidosisuremic toxinsintestinal bacteria toxinsimpaired calcium-phosphorus metabolismReferencesМуркамилов И. Т., Айтбаев К. А., Реджапова Н. А. и др. Нефрои церебропротекция при хронической болезни почек: возможности кандесартана. Кардиология. 2017;6:69-75. doi:10.18565/cardio.2017.6.69-75.Murkamilov IT, Aitbaev KA, Redzhapova NA, et al. Nephroand cerebroprotection in chronic kidney disease: opportunities of candesartan. Kardiologiia. 2017;6:69-75. (In Russ.) doi:10.18565/cardio.2017.6.69-75.Ягудина Р. И., Серпик В. Г., Абдрашитова Г. Т. и др. Экономическое бремя хронической болезни почек в Российской Федерации. Фармакоэкономика: теория и практика. 2014;2(4):34-9.Yagudina RI, Serpik VG, Аbdrashitova GT, et al. Economic burden of chronic kidney disease in the Russian Federation. Farmakoekonomika: Teoriya i Praktika. 2014;2(4):34-9. (In Russ.)Chen YC, Su Y-C, Lee C-C, et al. Chronic kidney disease itself is a causal risk factor for stroke beyond traditional cardiovascular risk factors: a nationwide cohort study in Taiwan. PLoS One. 2012;7(4):1-7. doi:10.1371/journal.pone.0036332.Chen YC, Su Y-C, Lee C-C, et al. Chronic kidney disease itself is a causal risk factor for stroke beyond traditional cardiovascular risk factors: a nationwide cohort study in Taiwan. PLoS One. 2012;7(4):1-7. doi:10.1371/journal.pone.0036332.Нестеренко О. В., Бородулин В. Б., Горемыкин В. И. и др. Значение гипергомоцистеинемии (ГГЦ) в патогенезе хронического пиелонефрита. Фундаментальные исследования. 2014;7(1):193-6.Nesterenko OV, Borodulin VB, Goremykin VI, et al. Importance of hyperhomocysteinemia (HHC) in chronic pyelonephritis. Fundamental research. 2014;7(1):193-6. (In Russ.)Зобова Д. А., Козлов С. А. Роль гомоцистеина в патогенезе некоторых заболеваний. Известия высших учебных заведений. Поволжский регион. Медицинские науки. 2016;3:132-44. doi:10.21685/2072-3032-2016-3-15.Zobova DA, Kozlov SA. The role of homocysteine in pathogenesis of certain diseases. University proceedings. Volga region. Medical sciences. 2016;3:132-44. (In Russ.) doi:10.21685/2072-3032-2016-3-15.Ефимов В. С., Озолиня Л. А., Кашежева А. З. и др. Гипергомоцистеинемия в клинической практике: руководство. М.: ГЭОТАР-Медиа; 2013. 80 с. ISBN 978-5-9704-2320-2.Efimov VS, Ozolinia LA, Kashezheva AZ, et al. Hyperhomocysteinemia in clinical practice: manual. M.: GEOTAR-Media; 2013. 80 p. (In Russ.) ISBN 978-5-9704-2320-2.Кузьмичев Д. Е., Скребов Р. В., Чирков С. В. и др. Амилоидоз. Здравоохранение Югры: опыт и инновации. 2016;1:59-64.Kuzmichev DE, Skrebov RV, Chirkov SV, et al. Amyloidosis. Zdravoohranenie Ugry: opyt i innovacii. 2016;1:59-64. (In Russ.)Ochiai H, Uezono S, Kawano H. Factors affecting outcome of intracerebral hemorrhage in patients undergoing chronic hemodialysis. Ren Fail. 2010;8(32):9237. doi:10.3109/0886022X.2010.502279.Ochiai H, Uezono S, Kawano H. Factors affecting outcome of intracerebral hemorrhage in patients undergoing chronic hemodialysis. Ren Fail. 2010;8(32):9237. doi:10.3109/0886022X.2010.502279.Минеральные и костные нарушения при хронической болезни почек (МКН-ХБП). https://qps.ru/7dya6. (08 мая 2018).Mineral and osteal disorders in chronic kidney disease (MOD-CKD). https://qps.ru/7dya6. (08 May 2018). (In Russ.)Hruska K, Mathew S, Lund R, et al. Hyperphosphatemia of chronic kidney disease. Kidney Int. 2008;4(2):148-57. doi:10.1038/ki.2008.130.Hruska K, Mathew S, Lund R, et al. Hyperphosphatemia of chronic kidney disease. Kidney Int. 2008;4(2):148-57. doi:10.1038/ki.2008.130.Lau WL, Ix JH. Clinical detection, risk factors, and cardiovascular consequences of medial arterial calcification: a pattern of vascular injury associated with aberrant mineral metabolism. Semin Nephrol. 2013;33(2):93-105. doi:10.1016/j.semnephrol.2012.12.011.Lau WL, Ix JH. Clinical detection, risk factors, and cardiovascular consequences of medial arterial calcification: a pattern of vascular injury associated with aberrant mineral metabolism. Semin Nephrol. 2013;33(2):93-105. doi:10.1016/j.semnephrol.2012.12.011.Steitz SA, Speer MY, Curinga G, et al. Smooth muscle cell phenotypic transition associated with calcification: upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circ Res. 2001;89(12):1147-54. doi:10.1161/hh2401.101070.Steitz SA, Speer MY, Curinga G, et al. Smooth muscle cell phenotypic transition associated with calcification: upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circ Res. 2001;89(12):1147-54. doi:10.1161/hh2401.101070.Hosaka N, Mizobuchi M, Ogata H, et al. Elastin degradation accelerates phosphateinduced mineralization of vascular smooth muscle cells. Calcif Tissue Int. 2009;85(6):523-9.Hosaka N, Mizobuchi M, Ogata H, et al. Elastin degradation accelerates phosphateinduced mineralization of vascular smooth muscle cells. Calcif Tissue Int. 2009;85(6):523-9.Shroff R, McNair R, Skepper JN, et al. Chronic mineral dysregulation promotes vascular smooth muscle cell adaptation and extracellular matrix calcification. J Am Soc Nephrol. 2010;21(1):103-12. doi:10.1681/ASN.2009060640.Shroff R, McNair R, Skepper JN, et al. Chronic mineral dysregulation promotes vascular smooth muscle cell adaptation and extracellular matrix calcification. J Am Soc Nephrol. 2010;21(1):103-12. doi:10.1681/ASN.2009060640.Gattineni J, Bates C, Twombley K, et al. FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1. Am J Physiol Renal Physiol. 2009;297(2):282-91. doi:10.1152/ajprenal.90742.2008.Gattineni J, Bates C, Twombley K, et al. FGF23 decreases renal NaPi-2a and NaPi-2c expression and induces hypophosphatemia in vivo predominantly via FGF receptor 1. Am J Physiol Renal Physiol. 2009;297(2):282-91. doi:10.1152/ajprenal.90742.2008.Chen T, Mao H, Chen C, et al. The role and mechanism of α-Klotho in the calcification of rat aortic vascular smooth muscle cells. Biomed Res Int. 2015;2015:17. doi:10.1155/2015/194362.Chen T, Mao H, Chen C, et al. The role and mechanism of α-Klotho in the calcification of rat aortic vascular smooth muscle cells. Biomed Res Int. 2015;2015:17. doi:10.1155/2015/194362.Hu MC, Shi M, Zhang J, et al. Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol. 2011;22(1):124-36. doi:10.1681/ASN.2009121311.Hu MC, Shi M, Zhang J, et al. Klotho deficiency causes vascular calcification in chronic kidney disease. J Am Soc Nephrol. 2011;22(1):124-36. doi:10.1681/ASN.2009121311.Schurgers LJ, Barreto DV, Barreto FC, et al. The circulating inactive form of matrix gla protein is a surrogate marker for vascular calcification in chronic kidney disease: a preliminary report. Clin J Am Soc Nephrol. 2010;5(4):568-75. doi:10.2215/ CJN.07081009.Schurgers LJ, Barreto DV, Barreto FC, et al. The circulating inactive form of matrix gla protein is a surrogate marker for vascular calcification in chronic kidney disease: a preliminary report. Clin J Am Soc Nephrol. 2010;5(4):568-75. doi:10.2215/ CJN.07081009.Watanabe K, Watanabe T, Nakayama M. Cerebro-renal interactions: impact of uremic toxins on cognitive function. Neurotoxicology. 2014;44:184-93. doi:10.1016/j.neuro.2014.06.014.Watanabe K, Watanabe T, Nakayama M. Cerebro-renal interactions: impact of uremic toxins on cognitive function. Neurotoxicology. 2014;44:184-93. doi:10.1016/j.neuro.2014.06.014.Bugnicourt JM, Da Silveira C, Bengrine A, et al. Chronic renal failure alters endothelial function in cerebral circulation in mice. Am J Physiol Heart Circ Physiol. 2011;301:1143-52. doi:10.1152/ajpheart.01237.2010.Bugnicourt JM, Da Silveira C, Bengrine A, et al. Chronic renal failure alters endothelial function in cerebral circulation in mice. Am J Physiol Heart Circ Physiol. 2011;301:1143-52. doi:10.1152/ajpheart.01237.2010.Watanabe H, Miyamoto Y, Otagiri M et al. Update on the pharmacokinetics and redox properties of protein-bound uremic toxins. J Pharm Sci. 2011;100:3682-95. doi:10.1002/jps.22592.Watanabe H, Miyamoto Y, Otagiri M et al. Update on the pharmacokinetics and redox properties of protein-bound uremic toxins. J Pharm Sci. 2011;100:3682-95. doi:10.1002/jps.22592.Six I, Maizel J, Barreto FC, et al. Effects of phosphate on vascular function under normal conditions and influence of the uraemic state. Cardiovasc Res. 2012;96:1309. doi:10.1093/cvr/cvs240.Six I, Maizel J, Barreto FC, et al. Effects of phosphate on vascular function under normal conditions and influence of the uraemic state. Cardiovasc Res. 2012;96:1309. doi:10.1093/cvr/cvs240.Muteliefu G, Enomoto A, Jiang P et al. Indoxyl sulphate induces oxidative stress and the expression of osteoblast-specific proteins in vascular smooth muscle cells. Nephrol Dial Transplant. 2009;24:2051-8. doi:10.1093/ndt/gfn757.Muteliefu G, Enomoto A, Jiang P et al. Indoxyl sulphate induces oxidative stress and the expression of osteoblast-specific proteins in vascular smooth muscle cells. Nephrol Dial Transplant. 2009;24:2051-8. doi:10.1093/ndt/gfn757.Vaziri ND, Yuan J, Rahimi A, et al. Disintegration of colonic epithelial tight junction in uremia: a likely cause of CKD-associated inflammation. Nephrol Dial Transplant. 2012;27(7):2686-93. doi:10.1093/ndt/gfr624.Vaziri ND, Yuan J, Rahimi A, et al. Disintegration of colonic epithelial tight junction in uremia: a likely cause of CKD-associated inflammation. Nephrol Dial Transplant. 2012;27(7):2686-93. doi:10.1093/ndt/gfr624.Szeto CC, Kwan BC-H, Chow K-M, et al. Endotoxemia is related to systemic inflammation and atherosclerosis in peritoneal dialysis patients. Clin J Am Soc Nephrol. 2008;3(2):431-6. doi:10.2215/CJN.03600807.Szeto CC, Kwan BC-H, Chow K-M, et al. Endotoxemia is related to systemic inflammation and atherosclerosis in peritoneal dialysis patients. Clin J Am Soc Nephrol. 2008;3(2):431-6. doi:10.2215/CJN.03600807.Lau WL, Kalantar-Zadeh K, Vaziri ND. The gut as a source of inflammation in chronic kidney disease. Nephron. 2015;130(2):92-8. doi:10.1159/000381990.Lau WL, Kalantar-Zadeh K, Vaziri ND. The gut as a source of inflammation in chronic kidney disease. Nephron. 2015;130(2):92-8. doi:10.1159/000381990.Vaziri ND, Yuan J, Norris K. Role of urea in intestinal barrier dysfunction and disruption of epithelial tight junction in chronic kidney disease. Am J Nephrol. 2013;37(1):1-6. doi:10.1159/000345969.Vaziri ND, Yuan J, Norris K. Role of urea in intestinal barrier dysfunction and disruption of epithelial tight junction in chronic kidney disease. Am J Nephrol. 2013;37(1):1-6. doi:10.1159/000345969.Lau WL, Liu S-M, Pahlevan S, et al. Role of Nrf2 dysfunction in uremia-associated intestinal inflammation and epithelial barrier disruption. Dig Dis Sci. 2014;60:1215-22.Lau WL, Liu S-M, Pahlevan S, et al. Role of Nrf2 dysfunction in uremia-associated intestinal inflammation and epithelial barrier disruption. Dig Dis Sci. 2014;60:1215-22.Feroze U, Kalantar-Zadeh K, Sterling KA, et al. Examining associations of circulating endotoxin with nutritional status, inflammation, and mortality in hemodialysis patients. J Ren Nutr. 2012;22(3):317-26. doi:10.1053/j.jrn.2011.05.004.Feroze U, Kalantar-Zadeh K, Sterling KA, et al. Examining associations of circulating endotoxin with nutritional status, inflammation, and mortality in hemodialysis patients. J Ren Nutr. 2012;22(3):317-26. doi:10.1053/j.jrn.2011.05.004.Rossi M, Campbell KL, Johnson DW, et al. Protein-bound uremic toxins, inflammation and oxidative stress: a cross-sectional study in stage 3-4 chronic kidney disease. Arch Med Res. 2014;45(4):309-17. doi:10.1016/j.arcmed.2014.04.002.Rossi M, Campbell KL, Johnson DW, et al. Protein-bound uremic toxins, inflammation and oxidative stress: a cross-sectional study in stage 3-4 chronic kidney disease. Arch Med Res. 2014;45(4):309-17. doi:10.1016/j.arcmed.2014.04.002.Tang WH, Wang Z, Kennedy DJ, et al. Gut microbiota-dependent Trimethylamine NOxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015;116(3):448-55. doi:10.1161/CIRCRESAHA.116.305360.Tang WH, Wang Z, Kennedy DJ, et al. Gut microbiota-dependent Trimethylamine NOxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015;116(3):448-55. doi:10.1161/CIRCRESAHA.116.305360.Yin J, Liao SX, He Y, et al. Dysbiosis of gut microbiota with reduced trimethylamineN-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack. J Am Heart Assoc. 2015;4(11):1-12. doi:10.1161/JAHA.115.002699.Yin J, Liao SX, He Y, et al. Dysbiosis of gut microbiota with reduced trimethylamineN-oxide level in patients with large-artery atherosclerotic stroke or transient ischemic attack. J Am Heart Assoc. 2015;4(11):1-12. doi:10.1161/JAHA.115.002699.Корж А. Н. Кардиоренальный синдром у больных хронической болезнью почек и ишемической болезнью сердца. Почки. 2015;1:45-51.Korzh AN. Cadiorenal syndrome in patients with cronic kidney disease and coronary heart disease. Pochki. 2015;1:45-51. (In Russ.)Chang YL, Hung SH, Ling W, et al. Association between ischemic stroke and irondeficiency anemia: a population-based study. PLoS One. 2013;8(12):1-7. doi:10.1371/journal.pone.0082952.Chang YL, Hung SH, Ling W, et al. Association between ischemic stroke and irondeficiency anemia: a population-based study. PLoS One. 2013;8(12):1-7. doi:10.1371/journal.pone.0082952.Seliger SL, Zhang AD, Weir MR, et al. Erythropoiesis-stimulating agents increase the risk of acute stroke in patients with chronic kidney disease. Kidney Int. 2011;80:28894. doi:10.1038/ki.2011.49.Seliger SL, Zhang AD, Weir MR, et al. Erythropoiesis-stimulating agents increase the risk of acute stroke in patients with chronic kidney disease. Kidney Int. 2011;80:28894. doi:10.1038/ki.2011.49.Vinhas J, Barreto C, Assuncao J, et al. Treatment of anaemia with erythropoiesisstimulating agents in patients with chronic kidney disease does not lower mortality and may increase cardiovascular risk: a meta-analysis. Nephron Clin Pract. 2012;121:95-101. doi:10.1159/000345158.Vinhas J, Barreto C, Assuncao J, et al. Treatment of anaemia with erythropoiesisstimulating agents in patients with chronic kidney disease does not lower mortality and may increase cardiovascular risk: a meta-analysis. Nephron Clin Pract. 2012;121:95-101. doi:10.1159/000345158.Palmer SC, Navaneethan SD, Craig JC, et al. Meta-analysis: erythropoiesisstimulating agents in patients with chronic kidney disease. Ann Intern Med. 2010;153:23-33. doi:10.7326/0003-4819-153-1-201007060-00252.Palmer SC, Navaneethan SD, Craig JC, et al. Meta-analysis: erythropoiesisstimulating agents in patients with chronic kidney disease. Ann Intern Med. 2010;153:23-33. doi:10.7326/0003-4819-153-1-201007060-00252.Chan KE, Lazarus JM, Thadhani R, et al. Anticoagulant and antiplatelet usage associates with mortality among hemodialysis patients. J Am Soc Nephrol. 2009;20:872-81. doi:10.1681/ASN.2008080824.Chan KE, Lazarus JM, Thadhani R, et al. Anticoagulant and antiplatelet usage associates with mortality among hemodialysis patients. J Am Soc Nephrol. 2009;20:872-81. doi:10.1681/ASN.2008080824.Lau WL, Huisa BN, Fisher M. The Cerebrovascular-Chronic Kidney Disease Connection: Perspectives and Mechanisms. Transl. Stroke Res. 2017;8:67-76.Lau WL, Huisa BN, Fisher M. The Cerebrovascular-Chronic Kidney Disease Connection: Perspectives and Mechanisms. Transl. Stroke Res. 2017;8:67-76.Charidimou A, Werring DJ. A raging fire in acute lacunar stroke: inflammation, bloodbrain barrier dysfunction and the origin of cerebral. J Neurol Sci. 2014;340(1-2):1-2. doi:10.1016/j.jns.2014.03.004.Charidimou A, Werring DJ. A raging fire in acute lacunar stroke: inflammation, bloodbrain barrier dysfunction and the origin of cerebral. J Neurol Sci. 2014;340(1-2):1-2. doi:10.1016/j.jns.2014.03.004.Xiao L, Sun W, Lan W, et al. Correlation between cerebral microbleeds and S100B/RAGE in acute lacunar stroke patients. J Neurol Sci. 2014;340(1-2):208-12. doi:10.1016/j.jns.2014.03.006.Xiao L, Sun W, Lan W, et al. Correlation between cerebral microbleeds and S100B/RAGE in acute lacunar stroke patients. J Neurol Sci. 2014;340(1-2):208-12. doi:10.1016/j.jns.2014.03.006.Isoyama N, Leurs P, Qureshi AR, et al. Plasma S100A12 and soluble receptor of advanced glycation end product levels and mortality in chronic kidney disease Stage 5 patients. Nephrol Dial Transplant. 2015;30(1):84-91. doi:10.1093/ndt/gfu259.Isoyama N, Leurs P, Qureshi AR, et al. Plasma S100A12 and soluble receptor of advanced glycation end product levels and mortality in chronic kidney disease Stage 5 patients. Nephrol Dial Transplant. 2015;30(1):84-91. doi:10.1093/ndt/gfu259.

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