nogrЭкспериментальная и клиническая гастроэнтерологияExperimental and Clinical Gastroenterology1682-8658«Global Media Technologies»10.31146/1682-8658-ecg-212-4-140-144nogr-2373Research ArticleОБЗОРREVIEWХроническая болезнь почек и неалкогольная жировая болезнь печени - новые патогенетические взаимосвязиChronic kidney disease and non-alcoholic fatty liver disease - new pathogenetic linkshttps://orcid.org/0000-0003-0091-2299КраснерЯ. А.KrasnerYa. A.noemail@neicon.ruhttps://orcid.org/0000-0002-9696-1302ОсипенкоМ. Ф.OsipenkoM. F.noemail@neicon.ruhttps://orcid.org/0000-0002-3016-2217ХолинС. И.HolinS. I.noemail@neicon.ruhttps://orcid.org/0000-0001-7912-0758ЛитвиноваН. В.LitvinovaN. V.noemail@neicon.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Новосибирский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияNovosibirsk State Medical UniversityRussian Federation20232607202304140144Copyright © Краснер Я.А., Осипенко М.Ф., Холин С.И., Литвинова Н.В., 20232023Краснер Я.А., Осипенко М.Ф., Холин С.И., Литвинова Н.В.Krasner Y.A., Osipenko M.F., Holin S.I., Litvinova N.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.nogr.org/jour/article/view/2373

В настоящей работе рассматриваются вопросы ассоциации неалкогольной жировой болезни печени (НАЖБП) и хронической болезни почек (ХБП). Существуют многочисленные данные о повышении риска ХБП при наличии НАЖБП. Большинство исследователей связывают это с общностью факторов риска для этих двух состояний. В настоящее время кроме традиционных факторов - компонентов метаболического синдрома, ассоциированных с ХБП и НАЖБП, рассматривается влияние новых патогенетических факторов, таких как эндотелиальная дисфункция, нарушения обмена фактора роста фибробластов - 21, патологическая активация ренин-ангиотензиновой системы и влияние изменений уровня адипонектина. Дальнейшее изучение этих механизмов может открыть новые терапевтические возможности в отношении лечения ХБП и НАЖБП.

This article discusses the association between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). There is ample evidence of an increased risk of CKD in patients with NAFLD. Most researchers attribute to the common risk factors for these two conditions. Currently, in addition to traditional factors associated with CKD and NAFLD, such as components of the metabolic syndrome, the influence of new pathogenetic factors, i. e. endothelial dysfunction, metabolic disorders of fibroblast growth factor-21, pathological activation of the renin-angiotensin system and influence of adiponectin level change are considered. Further examination of these mechanisms will open up new therapeutic options for the treatment of CKD and NAFLD.

хроническая болезнь почекнеалкогольная жировая болезнь печенифактор роса фибробластовренин-ангиотензиновая системаэндотелиальная дисфункцияchronic kidney diseasenon-alcoholic fatty liver diseasefibroblast dew factorrenin-angiotensin systemendothelial dysfunctionReferencesCarney E. F. The impact of chronic kidney disease on global health. Nat Rev Nephrol. 2020 May;16(5):251. doi: 10.1038/s41581-020-0268-7.Carney E. F. The impact of chronic kidney disease on global health. Nat Rev Nephrol. 2020 May;16(5):251. doi: 10.1038/s41581-020-0268-7.Liu Y., Zhong G. C., Tan H. Y., Hao F. B., Hu J. J. Nonalcoholic fatty liver disease and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis. Scientific Reports. 2019 Jul 31;9(1):11124. doi: 10.1038/s41598-019-47687-3.Liu Y., Zhong G. C., Tan H. Y., Hao F. B., Hu J. J. Nonalcoholic fatty liver disease and mortality from all causes, cardiovascular disease, and cancer: a meta-analysis. Scientific Reports. 2019 Jul 31;9(1):11124. doi: 10.1038/s41598-019-47687-3.Byrne C.D., Targher G. NAFLD: A multisystem disease. J. Hepatol. 2015 Apr;62(1 Suppl): S47-64. doi: 10.1016/j.jhep.2014.12.012.Byrne C.D., Targher G. NAFLD: A multisystem disease. J. Hepatol. 2015 Apr;62(1 Suppl): S47-64. doi: 10.1016/j.jhep.2014.12.012.Bakulin I.G., Sandler Yu.G., Vinnitskaya E. V., Keian V. A., Rodionova S. V., Rotin D. L. Sakharnyi diabet i nealkogol’naya zhirovaya bolezn’ pecheni: grani sopryazhennosti [Diabetes mellitus and nonalcoholic fatty liver disease: The verges of contingency]. Ter Arkh. 2017;89(2):59-65.Russian. doi: 10.17116/terarkh201789259-65.Bakulin I.G., Sandler Yu.G., Vinnitskaya E. V., Keian V. A., Rodionova S. V., Rotin D. L. Sakharnyi diabet i nealkogol’naya zhirovaya bolezn’ pecheni: grani sopryazhennosti [Diabetes mellitus and nonalcoholic fatty liver disease: The verges of contingency]. Ter Arkh. 2017;89(2):59-65.Russian. doi: 10.17116/terarkh201789259-65.Byrne C.D., Targher G. NAFLD as a driver of chronic kidney disease. J Hepatol. 2020 Apr;72(4):785-801. doi: 10.1016/j.jhep.2020.01.013.Byrne C.D., Targher G. NAFLD as a driver of chronic kidney disease. J Hepatol. 2020 Apr;72(4):785-801. doi: 10.1016/j.jhep.2020.01.013.Targher G., Bertolini L., Rodella S., Lippi G., Zoppini G., Chonchol M. Relationship between kidney function and liver histology in subjects with nonalcoholic steatohepatitis. Clin J Am Soc Nephrol. 2010 Dec;5(12):2166-71. doi: 10.2215/CJN.05050610.Targher G., Bertolini L., Rodella S., Lippi G., Zoppini G., Chonchol M. Relationship between kidney function and liver histology in subjects with nonalcoholic steatohepatitis. Clin J Am Soc Nephrol. 2010 Dec;5(12):2166-71. doi: 10.2215/CJN.05050610.Musso G., Gambino R., Tabibian J. H., Ekstedt M., Kechagias S., Hamaguchi M. et al. Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis. PLoS Med. 2014 Jul 22;11(7): e1001680. doi: 10.1371/journal.pmed.1001680.Musso G., Gambino R., Tabibian J. H., Ekstedt M., Kechagias S., Hamaguchi M. et al. Association of non-alcoholic fatty liver disease with chronic kidney disease: a systematic review and meta-analysis. PLoS Med. 2014 Jul 22;11(7): e1001680. doi: 10.1371/journal.pmed.1001680.Park H., Dawwas G. K., Liu X., Nguyen M. H.Nonalcoholic fatty liver disease increases risk of incident advanced chronic kidney disease: A propensity-matched cohort study. J Intern Med. 2019 Dec;286(6):711-722. doi: 10.1111/joim.12964.Park H., Dawwas G. K., Liu X., Nguyen M. H.Nonalcoholic fatty liver disease increases risk of incident advanced chronic kidney disease: A propensity-matched cohort study. J Intern Med. 2019 Dec;286(6):711-722. doi: 10.1111/joim.12964.Vilar-Gomez E., Calzadilla-Bertot L., Friedman S. L., Gra-Oramas B., Gonzalez-Fabian L., Villa-Jimenez O. et al. Improvement in liver histology due to lifestyle modification is independently associated with improved kidney function in patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2017 Jan;45(2):332-344. doi: 10.1111/apt.13860.Vilar-Gomez E., Calzadilla-Bertot L., Friedman S. L., Gra-Oramas B., Gonzalez-Fabian L., Villa-Jimenez O. et al. Improvement in liver histology due to lifestyle modification is independently associated with improved kidney function in patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2017 Jan;45(2):332-344. doi: 10.1111/apt.13860.Cao Y., Deng Y., Wang J., Zhao H., Zhang J., Xie W. The association between NAFLD and risk of chronic kidney disease: a cross-sectional study. Ther Adv Chronic Dis. 2021 Nov 9;12:20406223211048649. doi: 10.1177/20406223211048649.Cao Y., Deng Y., Wang J., Zhao H., Zhang J., Xie W. The association between NAFLD and risk of chronic kidney disease: a cross-sectional study. Ther Adv Chronic Dis. 2021 Nov 9;12:20406223211048649. doi: 10.1177/20406223211048649.Moody W.E., Edwards N. C., Madhani M. et al. Endothelial dysfunction and cardiovascular disease in early-stage chronic kidney disease: cause or association? Atherosclerosis. 2012 Jul;223(1):86-94. doi: 10.1016/j.atherosclerosis.2012.01.043.Moody W.E., Edwards N. C., Madhani M. et al. Endothelial dysfunction and cardiovascular disease in early-stage chronic kidney disease: cause or association? Atherosclerosis. 2012 Jul;223(1):86-94. doi: 10.1016/j.atherosclerosis.2012.01.043.Kurapova M. V., Nizyamova A. R., Romasheva E. P., Davydkin I. L. Endothelial dysfunction in patients with chronic kidney disease. Proceedings of the Samara Scientific Center of the Russian Academy of Sciences. 2013;15(3):1823-1826. (in Russ.)@@ Курапова М. В., Низямова А. Р., Ромашева Е. П., Давыдкин И. Л. Эндотелиальная дисфункция у больных хронической болезнь почек. Известия Самарского научного центра Российской академии наук. 2013, Том 15, N 3, С. 1823-1826.Kurapova M. V., Nizyamova A. R., Romasheva E. P., Davydkin I. L. Endothelial dysfunction in patients with chronic kidney disease. Proceedings of the Samara Scientific Center of the Russian Academy of Sciences. 2013;15(3):1823-1826. (in Russ.)@@ Курапова М. В., Низямова А. Р., Ромашева Е. П., Давыдкин И. Л. Эндотелиальная дисфункция у больных хронической болезнь почек. Известия Самарского научного центра Российской академии наук. 2013, Том 15, N 3, С. 1823-1826.Xin Z., Liu S., Niu J., Xu M., Wang T., Lu J. et al. The association of low-grade albuminuria with incident non-alcoholic fatty liver disease and non-invasive markers of liver fibrosis by glycaemia status. Liver Int. 2021 Jan;41(1):101-109. doi: 10.1111/liv.14649.Xin Z., Liu S., Niu J., Xu M., Wang T., Lu J. et al. The association of low-grade albuminuria with incident non-alcoholic fatty liver disease and non-invasive markers of liver fibrosis by glycaemia status. Liver Int. 2021 Jan;41(1):101-109. doi: 10.1111/liv.14649.Al-Hamoudi W., Alsadoon A., Hassanian M., Alkhalidi H., Abdo A., Nour M. et al. Endothelial dysfunction in nonalcoholic steatohepatitis with low cardiac disease risk. Sci Rep. 2020 Jun 1;10(1):8825. doi: 10.1038/s41598-020-65835-y.Al-Hamoudi W., Alsadoon A., Hassanian M., Alkhalidi H., Abdo A., Nour M. et al. Endothelial dysfunction in nonalcoholic steatohepatitis with low cardiac disease risk. Sci Rep. 2020 Jun 1;10(1):8825. doi: 10.1038/s41598-020-65835-y.Jose N., Vasant P. K., Kuliranka K. G. Study of Endothelial Dysfunction in Patients With Non-alcoholic Fatty Liver Disease. Cureus. 2021 Dec 19;13(12): e20515. doi: 10.7759/cureus.20515.Jose N., Vasant P. K., Kuliranka K. G. Study of Endothelial Dysfunction in Patients With Non-alcoholic Fatty Liver Disease. Cureus. 2021 Dec 19;13(12): e20515. doi: 10.7759/cureus.20515.Khukhlina O.S., Antoniv A. V., Mandryk O. Ye., Smandych V. S., Matushchak M. R. The role of endothelial dysfunction in the progression mechanisms of non-alcoholic steatohepatitis in patients with obesity and chronic kidney disease. Wiad Lek. 2019;72(4):523-526. PMID: 31055525.Khukhlina O.S., Antoniv A. V., Mandryk O. Ye., Smandych V. S., Matushchak M. R. The role of endothelial dysfunction in the progression mechanisms of non-alcoholic steatohepatitis in patients with obesity and chronic kidney disease. Wiad Lek. 2019;72(4):523-526. PMID: 31055525.Musso G., Cassader M., Cohney S., Pinach S., Saba F., Gambino R. Emerging Liver-Kidney Interactions in Nonalcoholic Fatty Liver Disease. Trends Mol. Med. 2015 Oct;21(10):645-662. doi: 10.1016/j.molmed.2015.08.005.Musso G., Cassader M., Cohney S., Pinach S., Saba F., Gambino R. Emerging Liver-Kidney Interactions in Nonalcoholic Fatty Liver Disease. Trends Mol. Med. 2015 Oct;21(10):645-662. doi: 10.1016/j.molmed.2015.08.005.Triozzi J., Richardson P. A., Parker Gregg L., Navaneethan S. D. Incidence and predictors of non-alcoholic fatty liver disease among patients with chronic kidney disease. Nephrol Dial Transplant. 2021 Jul 23;36(8):1546-1548. doi: 10.1093/ndt/gfab046.Triozzi J., Richardson P. A., Parker Gregg L., Navaneethan S. D. Incidence and predictors of non-alcoholic fatty liver disease among patients with chronic kidney disease. Nephrol Dial Transplant. 2021 Jul 23;36(8):1546-1548. doi: 10.1093/ndt/gfab046.Bataller R., Sancho-Bru P., Ginès P., Lora J. M., Al-Garawi A., Solé M. et al. Activated human hepatic stellate cells express the renin-angiotensin system and synthesize angiotensin II. Gastroenterology. 2003 Jul;125(1):117-25. doi: 10.1016/s0016-5085(03)00695-4.Bataller R., Sancho-Bru P., Ginès P., Lora J. M., Al-Garawi A., Solé M. et al. Activated human hepatic stellate cells express the renin-angiotensin system and synthesize angiotensin II. Gastroenterology. 2003 Jul;125(1):117-25. doi: 10.1016/s0016-5085(03)00695-4.Kohara M., Masuda T., Shiizaki K., Akimoto T., Watanabe Y., Honma S. et al. Association between circulating fibroblast growth factor 21 and mortality in end-stage renal disease. PLoS One. 2017 Jun 5;12(6): e0178971. doi: 10.1371/journal.pone.0178971.Kohara M., Masuda T., Shiizaki K., Akimoto T., Watanabe Y., Honma S. et al. Association between circulating fibroblast growth factor 21 and mortality in end-stage renal disease. PLoS One. 2017 Jun 5;12(6): e0178971. doi: 10.1371/journal.pone.0178971.Zhang C., Shao M., Yang H., Chen L., Yu L., Cong W. et al. Attenuation of hyperlipidemia- and diabetes-induced early-stage apoptosis and late-stage renal dysfunction via administration of fibroblast growth factor-21 is associated with suppression of renal inflammation. PLoS One. 2013 Dec 9;8(12): e82275. doi: 10.1371/journal.pone.0082275.Zhang C., Shao M., Yang H., Chen L., Yu L., Cong W. et al. Attenuation of hyperlipidemia- and diabetes-induced early-stage apoptosis and late-stage renal dysfunction via administration of fibroblast growth factor-21 is associated with suppression of renal inflammation. PLoS One. 2013 Dec 9;8(12): e82275. doi: 10.1371/journal.pone.0082275.Markan K. R. Defining “FGF21 Resistance” during obesity: Controversy, criteria and unresolved questions. F1000Res. 2018 Mar 7;7:289. doi: 10.12688/f1000research.14117.1.Markan K. R. Defining “FGF21 Resistance” during obesity: Controversy, criteria and unresolved questions. F1000Res. 2018 Mar 7;7:289. doi: 10.12688/f1000research.14117.1.Hui E. Y. L., Woo Y. C., Yeung C. Y., Chow W. S., Yuen M. M. A. et al. Circulating fibroblast growth factor 21 levels predict progressive kidney disease in subjects with type 2 diabetes and normoalbuminuria. J. Clin. Endocrinol. Metab. 2015 Apr;100(4):1368-75. doi: 10.1210/jc.2014-3465.Hui E. Y. L., Woo Y. C., Yeung C. Y., Chow W. S., Yuen M. M. A. et al. Circulating fibroblast growth factor 21 levels predict progressive kidney disease in subjects with type 2 diabetes and normoalbuminuria. J. Clin. Endocrinol. Metab. 2015 Apr;100(4):1368-75. doi: 10.1210/jc.2014-3465.Proshchai G.A., Vorokhobina N. V., Zagarskikh E. Y., Partsernyak S. A., Partsernyak A. S. Fibroblast growth factor 21 and its influence on metabolic processes in the human body. Vestnik of Saint Petersburg University. Medicine. 2018;13(1):38-45. (in Russ.) doi: 10.21638/11701/spbu11.2018.104.@@ Прощай Г. А., Ворохобина Н. В., Загарских Е. Ю., Парцерняк С. А., Парцерняк А. С. Фактор роста фибробластов 21 и его влияние на метаболические процессы в организме человека. Вестник Санкт-Петербургского университета, 2018, Т. 13, Вып. 1, С. 38-42. doi: 10.21638/11701/spbu11.2018.104.Proshchai G.A., Vorokhobina N. V., Zagarskikh E. Y., Partsernyak S. A., Partsernyak A. S. Fibroblast growth factor 21 and its influence on metabolic processes in the human body. Vestnik of Saint Petersburg University. Medicine. 2018;13(1):38-45. (in Russ.) doi: 10.21638/11701/spbu11.2018.104.@@ Прощай Г. А., Ворохобина Н. В., Загарских Е. Ю., Парцерняк С. А., Парцерняк А. С. Фактор роста фибробластов 21 и его влияние на метаболические процессы в организме человека. Вестник Санкт-Петербургского университета, 2018, Т. 13, Вып. 1, С. 38-42. doi: 10.21638/11701/spbu11.2018.104.Tucker B., Li H., Long X., Rye K. A., Ong K. L. Fibroblast growth factor 21 in non-alcoholic fatty liver disease. Metabolism. 2019 Dec;101:153994. doi: 10.1016/j.metabol.2019.153994.Tucker B., Li H., Long X., Rye K. A., Ong K. L. Fibroblast growth factor 21 in non-alcoholic fatty liver disease. Metabolism. 2019 Dec;101:153994. doi: 10.1016/j.metabol.2019.153994.Ohashi K., Ouchi N., Matsuzawa Y. Anti-inflammatory and anti-atherogenic properties of adiponectin. Biochimie. 2012 Oct;94(10):2137-42. doi: 10.1016/j.biochi.2012.06.008.Ohashi K., Ouchi N., Matsuzawa Y. Anti-inflammatory and anti-atherogenic properties of adiponectin. Biochimie. 2012 Oct;94(10):2137-42. doi: 10.1016/j.biochi.2012.06.008.Zoccali C., Postorino M., Marino C., Pizzini P., Cutrupi S., Tripepi G. Waist circumference modifies the relationship between the adipose tissue cytokines leptin and adiponectin and all-cause and cardiovascular mortality in haemodialysis patients. Journal of internal medicine. 2011 Feb;269(2):172-81. doi: 10.1111/j.1365-2796.2010.02288.x.Zoccali C., Postorino M., Marino C., Pizzini P., Cutrupi S., Tripepi G. Waist circumference modifies the relationship between the adipose tissue cytokines leptin and adiponectin and all-cause and cardiovascular mortality in haemodialysis patients. Journal of internal medicine. 2011 Feb;269(2):172-81. doi: 10.1111/j.1365-2796.2010.02288.x.Spranger J., Kroke A., Mohlig M., Bergmann M. M., Ristow M., Boeing H., Pfeiffer A. Adiponectin and protection against type 2 diabetes mellitus. Lancet. 2003 Jan 18;361(9353):226-8. doi: 10.1016/S0140-6736(03)12255-6. Erratum in: Lancet. 2002 Mar 22;361(9362):1060.Spranger J., Kroke A., Mohlig M., Bergmann M. M., Ristow M., Boeing H., Pfeiffer A. Adiponectin and protection against type 2 diabetes mellitus. Lancet. 2003 Jan 18;361(9353):226-8. doi: 10.1016/S0140-6736(03)12255-6. Erratum in: Lancet. 2002 Mar 22;361(9362):1060.Musso G., Gambino R., Durazzo M., Biroli G., Carello M., Faga E., Pacini G., De Michieli F., Rabbione L., Premoli A., Cassader M., Pagano G.: Adipokines in NASH: Postprandial lipid metabolism as a link between adiponectin and liver disease. Hepatology. 2005 Nov;42(5):1175-83. doi: 10.1002/hep.20896.Musso G., Gambino R., Durazzo M., Biroli G., Carello M., Faga E., Pacini G., De Michieli F., Rabbione L., Premoli A., Cassader M., Pagano G.: Adipokines in NASH: Postprandial lipid metabolism as a link between adiponectin and liver disease. Hepatology. 2005 Nov;42(5):1175-83. doi: 10.1002/hep.20896.Przybyciński J., Dziedziejko V., Puchałowicz K., Domański L., Pawlik A. Adiponectin in Chronic Kidney Disease.International Journal of Molecular Sciences. 2020 Dec 9;21(24):9375. doi: 10.3390/ijms21249375.Przybyciński J., Dziedziejko V., Puchałowicz K., Domański L., Pawlik A. Adiponectin in Chronic Kidney Disease.International Journal of Molecular Sciences. 2020 Dec 9;21(24):9375. doi: 10.3390/ijms21249375.Kuo I.C., Wu P. H., Lin H. Y., Niu S. W., Huang J. C., Hung C. C., Chiu Y. W., Chen H. C. The association of adiponectin with metabolic syndrome and clinical outcome in patients with non-diabetic chronic kidney disease. PLoS One. 2019 Jul 19;14(7): e0220158. doi: 10.1371/journal.pone.0220158.Kuo I.C., Wu P. H., Lin H. Y., Niu S. W., Huang J. C., Hung C. C., Chiu Y. W., Chen H. C. The association of adiponectin with metabolic syndrome and clinical outcome in patients with non-diabetic chronic kidney disease. PLoS One. 2019 Jul 19;14(7): e0220158. doi: 10.1371/journal.pone.0220158.Ix J.H., Sharma K. Mechanisms linking obesity, chronic kidney disease, and fatty liver disease: the roles of fetuin-A, adiponectin, and AMPK. J Am Soc Nephrol. 2010 Mar;21(3):406-12. doi: 10.1681/ASN.2009080820.Ix J.H., Sharma K. Mechanisms linking obesity, chronic kidney disease, and fatty liver disease: the roles of fetuin-A, adiponectin, and AMPK. J Am Soc Nephrol. 2010 Mar;21(3):406-12. doi: 10.1681/ASN.2009080820.

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