nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical University10.36485/1561-6274-2022-26-2-46-64nefr-2115Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEWS AND LECTURESСТРУКТУРНО-ФУНКЦИОНАЛЬНЫЕ НАРУШЕНИЯ КИШЕЧНОГО БАРЬЕРА И ХРОНИЧЕСКАЯ БОЛЕЗНЬ ПОЧЕК. ОБЗОР ЛИТЕРАТУРЫ. ЧАСТЬ IISTRUCTURAL AND FUNCTIONAL INTESTINAL BARRIER ABNORMALITIES AND CHRONIC KIDNEY DISEASE. LITERATURE REVIEW. PART IIhttps://orcid.org/0000-0002-5893-3191ПятченковМ. О.PyatchenkovM. O.

Пятченков Михаил Олегович, канд. мед. наук, кафедра нефрологии и эфферентной терапии

194044, Санкт-Петербург, ул. Академика Лебедева, д. 6Тел.: +7 (812) 5424314

Mikhail O. Pyatchenkov, PhD, Department of nephrology and blood purification

194044, St. PetersburgPhone: +7 (812) 5424314

pyatchenkovMD@yandex.ruhttps://orcid.org/0000-0002-9455-1043РумянцевА. Ш.RumyantsevA. S.

Румянцев Александр Шаликович, проф., д-р. мед. наук. Санкт-Петербургский государственный университет, кафедра факультетской терапии; Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова, кафедра пропедевтики внутренних болезней

199106, Санкт-Петербург, 21-я линия В.О., д. 8аТел.: +7(812)326-03-26 Тел.: +7(812)234-01-65

Alexandr Sh.Rumyantsev, MD, PhD, DMedSci. Department of Faculty Therapy, Saint Petersburg State University; Department of Propaedeutics of Internal Diseases, Pavlov First Saint Petersburg State Medical University

199106, St. PetersburgPhone: +7 (812) 3260326

rash.56@mail.ruhttps://orcid.org/0000-0002-3045-1721ЩербаковЕ. В.SherbakovE. V.

Щербаков Евгений Вячеславович, кафедра нефрологии и эфферентной терапии

194044, Санкт-Петербург, ул. Академика Лебедева, д. 6Тел.: +7 (812) 5424314

Evgeniy V.Scherbakov, Department of nephrology and blood purification

194044, St. PetersburgPhone: +7 (812) 5424314

evgenvmeda@mail.ruhttps://orcid.org/0000-0002-2867-044XМарковА. Г.MarkovA. G.

Марков Александр Георгиевич, проф., д-р. биол. наук, каф. общей физиологии

199034, Санкт-Петербург, Университетская наб., д. 7–9Тел.: +7(812) 3289589

Alexander G. Markov, D.Sc., professor, Department of GeneralPhysiology

199034, St. Petersburg, Universitetskaj nab. 7-9Phone: +7 (812) 3289589

a.markov@spbu.ruВоенно-медицинская академия им. С.М. КироваРоссияMilitary Medical Academy S.M. KirovRussian FederationСанкт-Петербургский государственный университет; Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. ПавловаРоссияSaint Petersburg State University; Pavlov First Saint Petersburg State Medical UniversityRussian FederationСанкт-Петербургский государственный университетРоссияSaint Petersburg State UniversityRussian Federation2022220620222624664Copyright © Пятченков М.О., Румянцев А.Ш., Щербаков Е.В., Марков А.Г., 20222022Пятченков М.О., Румянцев А.Ш., Щербаков Е.В., Марков А.Г.Pyatchenkov M.O., Rumyantsev A.S., Sherbakov E.V., Markov A.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/2115

Последние несколько десятилетий ознаменовались значительным прогрессом в изучении микробно-тканевого комплекса кишечника и его роли в патогенезе широкого круга заболеваний. Все больше данных подтверждают наличие дисфункции кишечного барьера, в том числе, при различных нефропатиях. Пациенты с хронической болезнью почек (ХБП) характеризуются специфическими нарушениями качественного и количественного состава кишечной микробиоты. Эти изменения способствуют увеличению ферментации пищевых белков в уремические токсины, такие как p-крезил сульфат, индоксил сульфат и триметиламиноксид (ТМАО), расстройствам механизмов иммунной толерантности слизистой оболочки, дезорганизации плотных контактов кишечного эпителия, что неизбежно ведет к повышению трансэпителиальной проницаемости. Транслокация бактерий и продуктов микробного метаболизма из просвета кишечника в системную циркуляцию ответственна за системное воспаление, которое в настоящее время рассматривается в качестве одной из ведущих причин прогрессирования ХБП и связанных с ней осложнений. Тем не менее, точные механизмы взаимодействия между кишечником и почками остаются малоизученными. Во второй части обзора дана подробная характеристика структурно-функциональным нарушениям слизисто-эпителиального барьера кишечника, выявляемым при различных нефропатиях. Обсуждаются механизмы индуцированного уремией повреждения кишечного эпителия, а также современные возможности терапевтической коррекции последствий дисфункции кишечного барьера у больных с ХБП.

The last few decades have been marked by significant progress in the investigation of the intestinal microbial-tissue complex and its role in the pathogenesis of a wide range of diseases. The presence of intestinal barrier dysfunction has also been confirmed in various nephropathies. Patients with chronic kidney disease (CKD) are characterized by specific alterations of the qualitative and quantitative composition of the gut microbiota. These changes contribute to an increase in the fermentation of food proteins into uremic toxins, such as p-cresyl sulfate, indoxyl sulfate and trimethylaminoxide, disorders of immune tolerance mechanisms of the mucous membrane, disorganization of intestinal epithelium tight junctions, which inevitably leads to an increase of transepithelial permeability. Translocation of bacteria and microbial metabolism products from the intestinal lumen into the systemic circulation is responsible for systemic inflammation, which is currently considered as one of the leading causes of the CKD progression and related complications. However, the exact mechanisms of gut-kidney interaction remain poorly understood. The second part of the review gives a detailed description of the structural and functional disorders of the intestinal muco-epithelial barrier identified in various nephropathies. The mechanisms of uremia-induced intestinal epithelial disruption are discussed, as well as the current therapeutic strategies that may attenuate consequences of intestinal barrier dysfunction in patients with CKD.

кишечный барьерплотные контактыкишечная проницаемостьхроническая болезнь почекуремияintestinal barriertight junctionintestinal permeabilitychronic kidney diseaseuremiaReferencesGagliardi A, Totino V, Cacciotti F et al. Rebuilding the Gut Microbiota Ecosystem. Int J Environ Res Public Health 2018;15(8):1679. doi:10.3390/ijerph15081679Gagliardi A, Totino V, Cacciotti F et al. Rebuilding the Gut Microbiota Ecosystem. Int J Environ Res Public Health 2018;15(8):1679. doi:10.3390/ijerph15081679Ткаченко ЕИ, Гриневич ВБ, Губонина ИВ и др. Болезни как следствие нарушений симбиотических взаимоотношений организма хозяина с микробиотой и патогенами Вестник Российской Военно-медицинской академии 2021;2(74):243–252. doi:10.17816/brmma58117Tkachenko EI, Grinevich VB, Gubonina IV et al. Disease as a result of violations of the symbiotic relationship between the host and the microbiota with pathogens. Bulletin of the Russian Military Medical Academy. 2021;23(2):243–252 (In Russ.). doi:10.17816/brmma.58117Chelakkot C, Ghim J, Ryu S. Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp Mol Med 2018;50(8):1–9. doi:10.1038/s12276-018-0126-xChelakkot C, Ghim J, Ryu S. Mechanisms regulating intestinal barrier integrity and its pathological implications. Exp Mol Med 2018;50(8):1–9. doi:10.1038/s12276-018-0126-xTurner J. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 2009;9(11):799–809. doi:10.1038/nri2653Turner J. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 2009;9(11):799–809. doi:10.1038/nri2653Camilleri M. Leaky gut: mechanisms, measurement and clinical implications in humans. Gut 2019;68(8):1516–1526. doi:10.1136/gutjnl-2019-318427Camilleri M. Leaky gut: mechanisms, measurement and clinical implications in humans. Gut 2019;68(8):1516–1526. doi:10.1136/gutjnl-2019-318427Vaziri N, Zhao Y, Pahl M. Altered intestinal microbial flora and impaired epithelial barrier structure and function in CKD: the nature, mechanisms, consequences and potential treatment. Nephrol Dial Transplant 2016;31(5):737–746. doi:10.1093/ndt/gfv095Vaziri N, Zhao Y, Pahl M. Altered intestinal microbial flora and impaired epithelial barrier structure and function in CKD: the nature, mechanisms, consequences and potential treatment. Nephrol Dial Transplant 2016;31(5):737–746. doi:10.1093/ndt/gfv095Rysz J, Franczyk B, Ławiński J et al. The Impact of CKD on Uremic Toxins and Gut Microbiota. Toxins (Basel) 2021;13(4):252. doi:10.3390/toxins13040252Rysz J, Franczyk B, Ławiński J et al. The Impact of CKD on Uremic Toxins and Gut Microbiota. Toxins (Basel) 2021;13(4):252. doi:10.3390/toxins13040252Пятченков МО, Марков АГ, Румянцев АШ. Структурнофункциональные нарушения кишечного барьера и хроническая болезнь почек. Обзор литературы. Часть I. Нефрология 2022;26(1):10–26. doi:10.36485/1561-6274-2022-26-1-10-26Pyatchenkov MO, Markov AG, Rumyantsev AS. Structural and functional intestinal barrier abnormalities and chronic kidney disease. Literature review. Part I. Nephrology (Saint-Petersburg) 2022;26(1):10–26 (In Russ.). doi:10.36485/1561-6274-2022-26-1-10-26Vaziri N, Zhao Y, Pahl M. Altered intestinal microbial flora and impaired epithelial barrier structure and function in CKD: the nature, mechanisms, consequences and potential treatment. Nephrol Dial Transplant 2016;31(5):737–746. doi:10.1093/ndt/gfv095Vaziri N, Zhao Y, Pahl M. Altered intestinal microbial flora and impaired epithelial barrier structure and function in CKD: the nature, mechanisms, consequences and potential treatment. Nephrol Dial Transplant 2016;31(5):737–746. doi:10.1093/ndt/gfv095Лукичев БГ, Румянцев АШ, Акименко В. Микробиота кишечника и хроническая болезнь почек. Сообщение первое. Нефрология 2018;22(4):57–73. doi:10.24884/1561-6274-2018-22-4-57-73Lukichev BG, Rumyantsev AS, Akimenko V. Colonic microbiota and chronic kidney disease. Message one. Nephrology (SaintPetersburg) 2018;22(4):57–73 (In Russ.). doi:10.24884/1561-6274-2018-22-4-57-73Magnusson M, Magnusson K, Sundqvist T, Denneberg T. Increased intestinal permeability to differently sized polyethylene glycols in uremic rats: effects of low- and high-protein diets. Nephron 1990;56(3):306–311. doi:10.1159/000186158Magnusson M, Magnusson K, Sundqvist T, Denneberg T. Increased intestinal permeability to differently sized polyethylene glycols in uremic rats: effects of low- and high-protein diets. Nephron 1990;56(3):306–311. doi:10.1159/000186158Magnusson M, Magnusson K, Sundqvist T, Denneberg T. Impaired intestinal barrier function measured by differently sized polyethylene glycols in patients with chronic renal failure. Gut 1991;32(7):754–759. doi:10.1136/gut.32.7.754Magnusson M, Magnusson K, Sundqvist T, Denneberg T. Impaired intestinal barrier function measured by differently sized polyethylene glycols in patients with chronic renal failure. Gut 1991;32(7):754–759. doi:10.1136/gut.32.7.754Vaziri N, 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):2686–2693. doi:10.1093/ndt/gfr624Vaziri N, 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):2686–2693. doi:10.1093/ndt/gfr624Vaziri N, Yuan J, Nazertehrani S et al. Chronic kidney disease causes disruption of gastric and small intestinal epithelial tight junction. Am J Nephrol 2013;38(2):99–103. doi:10.1159/000353764Vaziri N, Yuan J, Nazertehrani S et al. Chronic kidney disease causes disruption of gastric and small intestinal epithelial tight junction. Am J Nephrol 2013;38(2):99–103. doi:10.1159/000353764Gonzalez A, Krieg R, Massey H et al. Sodium butyrate ameliorates insulin resistance and renal failure in CKD rats by modulating intestinal permeability and mucin expression. Nephrol Dial Transplant 2019;34(5):783–794. doi:10.1093/ndt/gfy238Gonzalez A, Krieg R, Massey H et al. Sodium butyrate ameliorates insulin resistance and renal failure in CKD rats by modulating intestinal permeability and mucin expression. Nephrol Dial Transplant 2019;34(5):783–794. doi:10.1093/ndt/gfy238Yang J, Lim S, Ko Y et al. Intestinal barrier disruption and dysregulated mucosal immunity contribute to kidney fibrosis in chronic kidney disease. Nephrol Dial Transplant 2019;34(3):419–428. doi:10.1093/ndt/gfy172Yang J, Lim S, Ko Y et al. Intestinal barrier disruption and dysregulated mucosal immunity contribute to kidney fibrosis in chronic kidney disease. Nephrol Dial Transplant 2019;34(3):419–428. doi:10.1093/ndt/gfy172Zhou N, Shen Y, Fan L et al. The Characteristics of Intestinal-Barrier Damage in Rats With IgA Nephropathy. Am J Med Sci 2020;359(3):168–176. doi:10.1016/j.amjms.2019.11.011Zhou N, Shen Y, Fan L et al. The Characteristics of Intestinal-Barrier Damage in Rats With IgA Nephropathy. Am J Med Sci 2020;359(3):168–176. doi:10.1016/j.amjms.2019.11.011Kovács T, Kun L, Schmelczer M et al. Do intestinal hyperpermeability and the related food antigens play a role in the progression of IgA nephropathy? I. Study of intestinal permeability. Am J Nephrol 1996;16(6):500–505. doi:10.1159/000169050Kovács T, Kun L, Schmelczer M et al. Do intestinal hyperpermeability and the related food antigens play a role in the progression of IgA nephropathy? I. Study of intestinal permeability. Am J Nephrol 1996;16(6):500–505. doi:10.1159/000169050de Almeida Duarte J, de Aguilar-Nascimento J, Nascimento M, Nochi R Jr. Bacterial translocation in experimental uremia. Urol Res 2004;32(4):266–270. doi:10.1007/s00240-003-0381-7de Almeida Duarte J, de Aguilar-Nascimento J, Nascimento M, Nochi R Jr. Bacterial translocation in experimental uremia. Urol Res 2004;32(4):266–270. doi:10.1007/s00240-003-0381-7Bossola M, Sanguinetti M, Scribano D et al. Circulating bacterial-derived DNA fragments and markers of inflammation in chronic hemodialysis patients. Clin J Am Soc Nephrol 2009;4(2):379–385. doi:10.2215/CJN.03490708Bossola M, Sanguinetti M, Scribano D et al. Circulating bacterial-derived DNA fragments and markers of inflammation in chronic hemodialysis patients. Clin J Am Soc Nephrol 2009;4(2):379–385. doi:10.2215/CJN.03490708Wang F, Jiang H, Shi K et al. Gut bacterial translocation is associated with microinflammation in end-stage renal disease patients. Nephrology (Carlton) 2012;17(8):733–738. doi:10.1111/j.1440-1797.2012.01647.xWang F, Jiang H, Shi K et al. Gut bacterial translocation is associated with microinflammation in end-stage renal disease patients. Nephrology (Carlton) 2012;17(8):733–738. doi:10.1111/j.1440-1797.2012.01647.xFeroze U, Kalantar-Zadeh K, Sterling K et al. Examining associations of circulating endotoxin with nutritional status, inflammation, and mortality in hemodialysis patients. J Ren Nutr 2012;22(3):317–326. doi:10.1053/j.jrn.2011.05.004Feroze U, Kalantar-Zadeh K, Sterling K et al. Examining associations of circulating endotoxin with nutritional status, inflammation, and mortality in hemodialysis patients. J Ren Nutr 2012;22(3):317–326. doi:10.1053/j.jrn.2011.05.004Guo S, Al-Sadi R, Said H, Ma T. Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14. Am J Pathol 2013;182(2):375–387. doi:10.1016/j.ajpath.2012.10.014Guo S, Al-Sadi R, Said H, Ma T. Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14. Am J Pathol 2013;182(2):375–387. doi:10.1016/j.ajpath.2012.10.014Chaves L, Mc Skimming D, Bryniarski M et al. Chronic kidney disease, uremic milieu, and its effects on gut bacterial microbiota dysbiosis. Am J Physiol Renal Physiol 2018;315(3):F487–F502. doi:10.1152/ajprenal.00092.2018Chaves L, Mc Skimming D, Bryniarski M et al. Chronic kidney disease, uremic milieu, and its effects on gut bacterial microbiota dysbiosis. Am J Physiol Renal Physiol 2018;315(3):F487–F502. doi:10.1152/ajprenal.00092.2018Terawaki H, Yokoyama K, Yamada Y et al. Low-grade endotoxemia contributes to chronic inflammation in hemodialysis patients: examination with a novel lipopolysaccharide detection method. Ther Apher Dial 2010;14(5):477–482. doi:10.1111/j.1744-9987.2010.00815.xTerawaki H, Yokoyama K, Yamada Y et al. Low-grade endotoxemia contributes to chronic inflammation in hemodialysis patients: examination with a novel lipopolysaccharide detection method. Ther Apher Dial 2010;14(5):477–482. doi:10.1111/j.1744-9987.2010.00815.xPoesen R, Ramezani A, Claes K et al. Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKD. Clin J Am Soc Nephrol 2015;10(9):1525–1533. doi:10.2215/CJN.03100315Poesen R, Ramezani A, Claes K et al. Associations of Soluble CD14 and Endotoxin with Mortality, Cardiovascular Disease, and Progression of Kidney Disease among Patients with CKD. Clin J Am Soc Nephrol 2015;10(9):1525–1533. doi:10.2215/CJN.03100315Stubbs J, House J, Ocque A et al. Serum Trimethylamine-NOxide is Elevated in CKD and Correlates with Coronary Atherosclerosis Burden. J Am Soc Nephrol 2016;27(1):305–313. doi:10.1681/ASN.2014111063Stubbs J, House J, Ocque A et al. Serum Trimethylamine-NOxide is Elevated in CKD and Correlates with Coronary Atherosclerosis Burden. J Am Soc Nephrol 2016;27(1):305–313. doi:10.1681/ASN.2014111063Kim S, Song I. The clinical impact of gut microbiota in chronic kidney disease. Korean J Intern Med 2020;35(6):1305–1316. doi:10.3904/kjim.2020.411Kim S, Song I. The clinical impact of gut microbiota in chronic kidney disease. Korean J Intern Med 2020;35(6):1305–1316. doi:10.3904/kjim.2020.411Salguero M, Al-Obaide M, Singh R et al. Dysbiosis of Gram-negative gut microbiota and the associated serum lipopolysaccharide exacerbates inflammation in type 2 diabetic patients with chronic kidney disease. Exp Ther Med 2019;18(5):3461–3469. doi:10.3892/etm.2019.7943Salguero M, Al-Obaide M, Singh R et al. Dysbiosis of Gram-negative gut microbiota and the associated serum lipopolysaccharide exacerbates inflammation in type 2 diabetic patients with chronic kidney disease. Exp Ther Med 2019;18(5):3461–3469. doi:10.3892/etm.2019.7943Al-Obaide M, Singh R, Datta P et al. Gut Microbiota-Dependent Trimethylamine-N-oxide and Serum Biomarkers in Patients with T2DM and Advanced CKD. J Clin Med 2017;6(9):86. doi:10.3390/jcm6090086Al-Obaide M, Singh R, Datta P et al. Gut Microbiota-Dependent Trimethylamine-N-oxide and Serum Biomarkers in Patients with T2DM and Advanced CKD. J Clin Med 2017;6(9):86. doi:10.3390/jcm6090086Aronov P, Luo F, Plummer N et al. Colonic contribution to uremic solutes. J Am Soc Nephrol 2011;22(9):1769–1776. doi:10.1681/ASN.2010121220Aronov P, Luo F, Plummer N et al. Colonic contribution to uremic solutes. J Am Soc Nephrol 2011;22(9):1769–1776. doi:10.1681/ASN.2010121220Poesen R, Windey K, Neven E et al. The Influence of CKD on Colonic Microbial Metabolism. J Am Soc Nephrol 2016;27(5):1389–1399. doi:10.1681/ASN.2015030279Poesen R, Windey K, Neven E et al. The Influence of CKD on Colonic Microbial Metabolism. J Am Soc Nephrol 2016;27(5):1389–1399. doi:10.1681/ASN.2015030279Vanholder R, Pletinck A, Schepers E, Glorieux G. Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update. Toxins 2018;10(1): 33. doi:10.3390/toxins10010033Vanholder R, Pletinck A, Schepers E, Glorieux G. Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update. Toxins 2018;10(1): 33. doi:10.3390/toxins10010033Gryp T, De Paepe K, Vanholder R et al. Gut microbiota generation of protein-bound uremic toxins and related metabolites is not altered at different stages of chronic kidney disease. Kidney Int 2020;97(6):1230–1242. doi:10.1016/j.kint.2020.01.028Gryp T, De Paepe K, Vanholder R et al. Gut microbiota generation of protein-bound uremic toxins and related metabolites is not altered at different stages of chronic kidney disease. Kidney Int 2020;97(6):1230–1242. doi:10.1016/j.kint.2020.01.028Wang X, Yang S, Li S et al. Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents. Gut 2020;69(12):2131-2142. doi:10.1136/gutjnl-2019-319766Wang X, Yang S, Li S et al. Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents. Gut 2020;69(12):2131-2142. doi:10.1136/gutjnl-2019-319766Fasano A, Not T, Wang W et al. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet 2000;355(9214):1518–1519. doi:10.1016/S0140-6736(00)02169-3Fasano A, Not T, Wang W et al. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet 2000;355(9214):1518–1519. doi:10.1016/S0140-6736(00)02169-3Leech B, Schloss J, Steel A. Association between increased intestinal permeability and disease: A systematic review. Adv Integr Med 2019;6:23–34. doi:10.1016/j.aimed.2018.08.003Leech B, Schloss J, Steel A. Association between increased intestinal permeability and disease: A systematic review. Adv Integr Med 2019;6:23–34. doi:10.1016/j.aimed.2018.08.003Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers 2016;4(4):e1251384. doi:10.1080/21688370.2016.1251384Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers 2016;4(4):e1251384. doi:10.1080/21688370.2016.1251384Ficek J, Wyskida K, Ficek R et al. Relationship between plasma levels of zonulin, bacterial lipopolysaccharides, D-lactate and markers of inflammation in haemodialysis patients. Int UrolNephrol 2017;49(4):717–725. doi:10.1007/s11255-016-1495-5Ficek J, Wyskida K, Ficek R et al. Relationship between plasma levels of zonulin, bacterial lipopolysaccharides, D-lactate and markers of inflammation in haemodialysis patients. Int UrolNephrol 2017;49(4):717–725. doi:10.1007/s11255-016-1495-5Carpes L, Nicoletto B, Canani L et al. Could serum zonulin be an intestinal permeability marker in diabetes kidney disease? PLoS One. 2021;16(6):e0253501. doi:10.1371/journal.pone.0253501Carpes L, Nicoletto B, Canani L et al. Could serum zonulin be an intestinal permeability marker in diabetes kidney disease? PLoS One. 2021;16(6):e0253501. doi:10.1371/journal.pone.0253501Sirin F, Korkmaz H, Eroglu I et al. Serum zonulin levels in type 2 diabetes patients with diabetic kidney disease. Endokrynol Pol 2021;72(5):545–549. doi:10.5603/EP.a2021.0056Sirin F, Korkmaz H, Eroglu I et al. Serum zonulin levels in type 2 diabetes patients with diabetic kidney disease. Endokrynol Pol 2021;72(5):545–549. doi:10.5603/EP.a2021.0056Hasslacher C, Kulozik F, Platten I et al. Serum zonulin as parameter of intestinal permeability in longstanding type 2 diabetes: correlations with metabolism parameter and renal function. J Diabetes Metab Disord Control 2018;5(2):58–62. doi:10.15406/jdmdc.2018.05.00138Hasslacher C, Kulozik F, Platten I et al. Serum zonulin as parameter of intestinal permeability in longstanding type 2 diabetes: correlations with metabolism parameter and renal function. J Diabetes Metab Disord Control 2018;5(2):58–62. doi:10.15406/jdmdc.2018.05.00138Dschietzig T, Boschann F, Ruppert J et al. Plasma Zonulin and its Association with Kidney Function, Severity of Heart Failure, and Metabolic Inflammation. Clin Lab 2016;62(12):2443–2447. doi:10.7754/Clin.Lab.2016.160512Dschietzig T, Boschann F, Ruppert J et al. Plasma Zonulin and its Association with Kidney Function, Severity of Heart Failure, and Metabolic Inflammation. Clin Lab 2016;62(12):2443–2447. doi:10.7754/Clin.Lab.2016.160512Lukaszyk E, Lukaszyk M, Koc-Zorawska E et al. Zonulin, inflammation and iron status in patients with early stages of chronic kidney disease. Int Urol Nephrol 2018;50(1):121–125. doi:10.1007/s11255-017-1741-5Lukaszyk E, Lukaszyk M, Koc-Zorawska E et al. Zonulin, inflammation and iron status in patients with early stages of chronic kidney disease. Int Urol Nephrol 2018;50(1):121–125. doi:10.1007/s11255-017-1741-5Malyszko J, Koc-Zorawska E, Levin-Iaina N, Malyszko J. Zonulin, iron status, and anemia in kidney transplant recipients: are they related? Transplant Proc 2014 Oct;46(8):2644–2646. doi:10.1016/j.transproceed.2014.09.018. PMID:25380885.Malyszko J, Koc-Zorawska E, Levin-Iaina N, Malyszko J. Zonulin, iron status, and anemia in kidney transplant recipients: are they related? Transplant Proc 2014 Oct;46(8):2644–2646. doi:10.1016/j.transproceed.2014.09.018. PMID:25380885.Trachtman H, Gipson D, Lemley K et al. Plasma Zonulin Levels in Childhood Nephrotic Syndrome. Front Pediatr 2019;7:197. doi:10.3389/fped.2019.00197Trachtman H, Gipson D, Lemley K et al. Plasma Zonulin Levels in Childhood Nephrotic Syndrome. Front Pediatr 2019;7:197. doi:10.3389/fped.2019.00197Okada K, Sekino M, Funaoka H et al. Intestinal fatty acidbinding protein levels in patients with chronic renal failure. J Surg Res 2018;230:94–100. doi:10.1016/j.jss.2018.04.057Okada K, Sekino M, Funaoka H et al. Intestinal fatty acidbinding protein levels in patients with chronic renal failure. J Surg Res 2018;230:94–100. doi:10.1016/j.jss.2018.04.057Swift O, Vilar E, Farrington K. Unexplained inflammation in end-stage kidney disease: Is the combination of enhanced gastrointestinal permeability and reticuloendothelial dysfunction its cause? Semin Dial 2019;32(5):417–423. doi:10.1111/sdi.12810Swift O, Vilar E, Farrington K. Unexplained inflammation in end-stage kidney disease: Is the combination of enhanced gastrointestinal permeability and reticuloendothelial dysfunction its cause? Semin Dial 2019;32(5):417–423. doi:10.1111/sdi.12810Wang S, Lv D, Jiang S et al. Quantitative reduction in shortchain fatty acids, especially butyrate, contributes to the progression of chronic kidney disease. Clin Sci (Lond) 2019;133(17):1857–1870. doi:10.1042/CS20190171Wang S, Lv D, Jiang S et al. Quantitative reduction in shortchain fatty acids, especially butyrate, contributes to the progression of chronic kidney disease. Clin Sci (Lond) 2019;133(17):1857–1870. doi:10.1042/CS20190171Borges N, Barros A, Nakao L et al. Protein-Bound Uremic Toxins from Gut Microbiota and Inflammatory Markers in Chronic Kidney Disease. J Ren Nutr 2016;26(6):396–400. doi:10.1053/j.jrn.2016.07.005Borges N, Barros A, Nakao L et al. Protein-Bound Uremic Toxins from Gut Microbiota and Inflammatory Markers in Chronic Kidney Disease. J Ren Nutr 2016;26(6):396–400. doi:10.1053/j.jrn.2016.07.005Aguilera A, Bajo M, Espinoza M et al. Gastrointestinal and pancreatic function in peritoneal dialysis patients: their relationship with malnutrition and peritoneal membrane abnormalities. Am J Kidney Dis 2003;42(4):787–796. doi:10.1016/s0272-6386(03)00920-xAguilera A, Bajo M, Espinoza M et al. Gastrointestinal and pancreatic function in peritoneal dialysis patients: their relationship with malnutrition and peritoneal membrane abnormalities. Am J Kidney Dis 2003;42(4):787–796. doi:10.1016/s0272-6386(03)00920-xTerpstra M, Singh R, Geerlings S, Bemelman F. Measurement of the intestinal permeability in chronic kidney disease. World J Nephrol 2016;5(4):378–388. doi:10.5527/wjn.v5.i4.378Terpstra M, Singh R, Geerlings S, Bemelman F. Measurement of the intestinal permeability in chronic kidney disease. World J Nephrol 2016;5(4):378–388. doi:10.5527/wjn.v5.i4.378Vaziri N, Goshtasbi N, Yuan J et al. Uremic plasma impairs barrier function and depletes the tight junction protein constituents of intestinal epithelium. Am J Nephrol 2012;36(5):438–443. doi:10.1159/000343886Vaziri N, Goshtasbi N, Yuan J et al. Uremic plasma impairs barrier function and depletes the tight junction protein constituents of intestinal epithelium. Am J Nephrol 2012;36(5):438–443. doi:10.1159/000343886Vaziri N, 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:10.1159/000345969Vaziri N, 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:10.1159/000345969Garcia A, Macedo M, Azevedo M et al. Effect of uremic state in intestine through a co-culture in vitro intestinal epithelial model. Int J Pharm 2020;584:119450. doi:10.1016/j.ijpharm.2020.119450Garcia A, Macedo M, Azevedo M et al. Effect of uremic state in intestine through a co-culture in vitro intestinal epithelial model. Int J Pharm 2020;584:119450. doi:10.1016/j.ijpharm.2020.119450Yang J, Lim S, Ko Y et al. Intestinal barrier disruption and dysregulated mucosal immunity contribute to kidney fibrosis in chronic kidney disease. Nephrol Dial Transplant 2019;34(3):419–428. doi:10.1093/ndt/gfy172Yang J, Lim S, Ko Y et al. Intestinal barrier disruption and dysregulated mucosal immunity contribute to kidney fibrosis in chronic kidney disease. Nephrol Dial Transplant 2019;34(3):419–428. doi:10.1093/ndt/gfy172Coopersmith C, Chang K, Swanson P et al. Overexpression of Bcl-2 in the intestinal epithelium improves survival in septic mice. Crit Care Med 2002;30(1):195–201. doi:10.1097/00003246-200201000-00028Coopersmith C, Chang K, Swanson P et al. Overexpression of Bcl-2 in the intestinal epithelium improves survival in septic mice. Crit Care Med 2002;30(1):195–201. doi:10.1097/00003246-200201000-00028Borges T, Wieten L, van Herwijnen M et al. The antiinflammatory mechanisms of Hsp70. Front Immunol 2012; 3:95. doi:10.3389/fimmu.2012.00095Borges T, Wieten L, van Herwijnen M et al. The antiinflammatory mechanisms of Hsp70. Front Immunol 2012; 3:95. doi:10.3389/fimmu.2012.00095Samborski P, Grzymisławski M. The role of HSP70 heat shock proteins in the pathogenesis and treatment of inflammatory bowel diseases. Adv Clin Exp Med 2015;24:525–530. doi:10.17219/acem/44144Samborski P, Grzymisławski M. The role of HSP70 heat shock proteins in the pathogenesis and treatment of inflammatory bowel diseases. Adv Clin Exp Med 2015;24:525–530. doi:10.17219/acem/44144Maciel R, Cunha R, Busato V et al. Uremia Impacts VECadherin and ZO-1 Expression in Human Endothelial Cell-to-Cell Junctions. Toxins (Basel) 2018;10(10):404. doi:10.3390/toxins10100404Maciel R, Cunha R, Busato V et al. Uremia Impacts VECadherin and ZO-1 Expression in Human Endothelial Cell-to-Cell Junctions. Toxins (Basel) 2018;10(10):404. doi:10.3390/toxins10100404Contreras-Velázquez J, Soto V, Jaramillo-Rodríguez Y et al. Clinical outcomes and peritoneal histology in patients starting peritoneal dialysis are related to diabetic status and serum albumin levels. Kidney Int Suppl 2008;(108):S34–41. doi:10.1038/sj.ki.5002599Contreras-Velázquez J, Soto V, Jaramillo-Rodríguez Y et al. Clinical outcomes and peritoneal histology in patients starting peritoneal dialysis are related to diabetic status and serum albumin levels. Kidney Int Suppl 2008;(108):S34–41. doi:10.1038/sj.ki.5002599Combet S, Ferrier M, Landschoot M et al. Chronic uremia induces permeability changes, increased nitric oxide synthase expression, and structural modifications in the peritoneum. J Am Soc Nephrol 2001;12(10):2146–2157. doi:10.1681/ASN.V12102146Combet S, Ferrier M, Landschoot M et al. Chronic uremia induces permeability changes, increased nitric oxide synthase expression, and structural modifications in the peritoneum. J Am Soc Nephrol 2001;12(10):2146–2157. doi:10.1681/ASN.V12102146Retana C, Sanchez E, Perez-Lopez A et al. Alterations of intercellular junctions in peritoneal mesothelial cells from patients undergoing dialysis: effect of retinoic Acid. Perit Dial Int 2015;35(3):275–287. doi:10.3747/pdi.2012.00323Retana C, Sanchez E, Perez-Lopez A et al. Alterations of intercellular junctions in peritoneal mesothelial cells from patients undergoing dialysis: effect of retinoic Acid. Perit Dial Int 2015;35(3):275–287. doi:10.3747/pdi.2012.00323McIntyre C, Harrison L, Eldehni M et al. Circulating endotoxemia: a novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease. Clin J Am Soc Nephrol 2011;6(1):133–141. doi:10.2215/CJN.04610510McIntyre C, Harrison L, Eldehni M et al. Circulating endotoxemia: a novel factor in systemic inflammation and cardiovascular disease in chronic kidney disease. Clin J Am Soc Nephrol 2011;6(1):133–141. doi:10.2215/CJN.04610510Khanna A, Rossman J, Fung H, Caty M. Intestinal and hemodynamic impairment following mesenteric ischemia/reperfusion. J Surg Res 2001;99(1):114–119. doi:10.1006/jsre.2001.6103Khanna A, Rossman J, Fung H, Caty M. Intestinal and hemodynamic impairment following mesenteric ischemia/reperfusion. J Surg Res 2001;99(1):114–119. doi:10.1006/jsre.2001.6103Stewart A, Pratt-Phillips S, Gonzalez L. Alterations in Intestinal Permeability: The Role of the "Leaky Gut" in Health and Disease. J Equine Vet Sci 2017;52:10–22. doi:10.1016/j.jevs.2017.02.009Stewart A, Pratt-Phillips S, Gonzalez L. Alterations in Intestinal Permeability: The Role of the "Leaky Gut" in Health and Disease. J Equine Vet Sci 2017;52:10–22. doi:10.1016/j.jevs.2017.02.009Wu T, Lim P, Jin J et al. Impaired Gut Epithelial Tight Junction Expression in Hemodialysis Patients Complicated with Intradialytic Hypotension. Biomed Res Int 2018;2018:2670312. doi:10.1155/2018/2670312Wu T, Lim P, Jin J et al. Impaired Gut Epithelial Tight Junction Expression in Hemodialysis Patients Complicated with Intradialytic Hypotension. Biomed Res Int 2018;2018:2670312. doi:10.1155/2018/2670312Gerson L. The presence of hemodialysis has been associated with GI hemorrhage, likely owing to intermittent usage of heparin for dialysis treatments and the presence of uremia-induced platelet dysfunction. Am J Med 1985;79: 552–559Gerson L. The presence of hemodialysis has been associated with GI hemorrhage, likely owing to intermittent usage of heparin for dialysis treatments and the presence of uremia-induced platelet dysfunction. Am J Med 1985;79: 552–559Jefferies H, Crowley L, Harrison L et al. Circulating endotoxaemia and frequent haemodialysis schedules. Nephron Clin Pract 2014;128(1-2):141–146. doi:10.1159/000366519Jefferies H, Crowley L, Harrison L et al. Circulating endotoxaemia and frequent haemodialysis schedules. Nephron Clin Pract 2014;128(1-2):141–146. doi:10.1159/000366519Freire E, Albuquerque J, Leal I et al. Effect of chronic renal dysfunction on the permeability of the colon to water and electrolytes: experimental study in rats. Arq Bras Cir Dig 2019;32(4):e1472. doi:10.1590/0102-672020190001e1472Freire E, Albuquerque J, Leal I et al. Effect of chronic renal dysfunction on the permeability of the colon to water and electrolytes: experimental study in rats. Arq Bras Cir Dig 2019;32(4):e1472. doi:10.1590/0102-672020190001e1472Rola F, Dos-Santos A, Xavier-Neto J et al. Effects of acute volemic changes on jejunal compliance in dogs. Braz J Med Biol Res 1989;22(4):523–531. PMID: 2590735.Rola F, Dos-Santos A, Xavier-Neto J et al. Effects of acute volemic changes on jejunal compliance in dogs. Braz J Med Biol Res 1989;22(4):523–531. PMID: 2590735.Graça J, Leal P, Gondim F et al. Variations in gastric compliance induced by acute blood volume changes in anesthetized rats. Braz J Med Biol Res 2002;35(3):405–410. doi:10.1590/s0100-879x2002000300018Graça J, Leal P, Gondim F et al. Variations in gastric compliance induced by acute blood volume changes in anesthetized rats. Braz J Med Biol Res 2002;35(3):405–410. doi:10.1590/s0100-879x2002000300018Andersen K, Kesper M, Marschner J et al. Intestinal Dysbiosis, Barrier Dysfunction, and Bacterial Translocation Account for CKD-Related Systemic Inflammation. J Am Soc Nephrol 2017;28(1):76–83. doi:10.1681/ASN.2015111285Andersen K, Kesper M, Marschner J et al. Intestinal Dysbiosis, Barrier Dysfunction, and Bacterial Translocation Account for CKD-Related Systemic Inflammation. J Am Soc Nephrol 2017;28(1):76–83. doi:10.1681/ASN.2015111285Meijers B, Farré R, Dejongh S et al. Intestinal Barrier Function in Chronic Kidney Disease. Toxins (Basel) 2018;10(7):298. doi:10.3390/toxins10070298Meijers B, Farré R, Dejongh S et al. Intestinal Barrier Function in Chronic Kidney Disease. Toxins (Basel) 2018;10(7):298. doi:10.3390/toxins10070298Nagura M, Tamura Y, Kumagai T et al. Uric acid metabolism of kidney and intestine in a rat model of chronic kidney disease. Nucleosides Nucleotides Nucleic Acids 2016;35(10-12):550–558. doi:10.1080/15257770.2016.1163379Nagura M, Tamura Y, Kumagai T et al. Uric acid metabolism of kidney and intestine in a rat model of chronic kidney disease. Nucleosides Nucleotides Nucleic Acids 2016;35(10-12):550–558. doi:10.1080/15257770.2016.1163379Shinozaki Y, Furuichi K, Toyama T et al. Impairment of the carnitine/organic cation transporter 1-ergothioneine axis is mediated by intestinal transporter dysfunction in chronic kidney disease. Kidney Int 2017;92(6):1356–1369. doi:10.1016/j.kint.2017.04.032Shinozaki Y, Furuichi K, Toyama T et al. Impairment of the carnitine/organic cation transporter 1-ergothioneine axis is mediated by intestinal transporter dysfunction in chronic kidney disease. Kidney Int 2017;92(6):1356–1369. doi:10.1016/j.kint.2017.04.032Masereeuw R, Mutsaers H, Toyohara T et al. The kidney and uremic toxin removal: glomerulus or tubule? Semin Nephrol 2014;34(2):191–208. doi:10.1016/j.semnephrol.2014.02.010Masereeuw R, Mutsaers H, Toyohara T et al. The kidney and uremic toxin removal: glomerulus or tubule? Semin Nephrol 2014;34(2):191–208. doi:10.1016/j.semnephrol.2014.02.010Liu B, Luo F, Luo X et al. Metabolic Enzyme System and Transport Pathways in Chronic Kidney Diseases. Curr Drug Metab 2018;19(7):568–576. doi:10.2174/1389200219666180103143448Liu B, Luo F, Luo X et al. Metabolic Enzyme System and Transport Pathways in Chronic Kidney Diseases. Curr Drug Metab 2018;19(7):568–576. doi:10.2174/1389200219666180103143448Смирнов АВ, Румянцев АШ. Острое повреждение почек. Часть I. Нефрология 2020;24(1):67–95. doi:10.36485/1561-6274-2020-24-1-67-95Smirnov AV, Rumyantsev AS. Acute kidney disease. Part I. Nephrology (Saint-Petersburg) 2020;24(1):67–95 (In Russ.). doi:10.36485/1561-6274-2020-24-1-67-95Смирнов АВ, Румянцев АШ. Острое повреждение почек. Часть II. Нефрология 2020;24(2):96–128. doi:10.36485/1561-6274-2020-24-2-96-128Smirnov AV, Rumyantsev AS. Acute kidney disease. Part II. Nephrology (Saint-Petersburg) 2020;24(2):96–128 (In Russ.). doi:10.36485/1561-6274-2020-24-2-96-128Kobayashi T, Iwata Y, Nakade Y, Wada T. Significance of the Gut Microbiota in Acute Kidney Injury. Toxins 2021;13(6):369. doi:10.3390/toxins13060369Kobayashi T, Iwata Y, Nakade Y, Wada T. Significance of the Gut Microbiota in Acute Kidney Injury. Toxins 2021;13(6):369. doi:10.3390/toxins13060369Rydzewska-Rosołowska A, Sroka N, Kakareko K et al. The Links between Microbiome and Uremic Toxins in Acute Kidney Injury: Beyond Gut Feeling-A Systematic Review. Toxins 2020;12(12):788. doi:10.3390/toxins12120788Rydzewska-Rosołowska A, Sroka N, Kakareko K et al. The Links between Microbiome and Uremic Toxins in Acute Kidney Injury: Beyond Gut Feeling-A Systematic Review. Toxins 2020;12(12):788. doi:10.3390/toxins12120788Park S, Chen S, Kim M et al. Cytokines induce small intestine and liver injury after renal ischemia or nephrectomy. Lab Invest 2011;91:63–84. doi:10.1038/labinvest.2010.151Park S, Chen S, Kim M et al. Cytokines induce small intestine and liver injury after renal ischemia or nephrectomy. Lab Invest 2011;91:63–84. doi:10.1038/labinvest.2010.151Yang J, Kim C, Go Y et al. Intestinal microbiota control acute kidney injury severity by immune modulation. Kidney Int 2020;98(4):932–946. doi:10.1016/j.kint.2020.04.048Yang J, Kim C, Go Y et al. Intestinal microbiota control acute kidney injury severity by immune modulation. Kidney Int 2020;98(4):932–946. doi:10.1016/j.kint.2020.04.048Vaziri N, Liu S, Lau W et al. High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease. PloS one 2014;9(12):e114881. doi:10.1371/journal.pone.0114881Vaziri N, Liu S, Lau W et al. High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease. PloS one 2014;9(12):e114881. doi:10.1371/journal.pone.0114881Sirich T, Plummer N, Gardner C et al. Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients. CJASN 2014;9(9):1603–1610. doi:10.2215/CJN.00490114Sirich T, Plummer N, Gardner C et al. Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients. CJASN 2014;9(9):1603–1610. doi:10.2215/CJN.00490114Krishnamurthy V, Wei G, Baird B et al. High dietary fiber intake is associated with decreased inflammation and all-cause mortality in patients with chronic kidney disease. Kidney international 2012;81(3):300–306. doi:10.1038/ki.2011.355Krishnamurthy V, Wei G, Baird B et al. High dietary fiber intake is associated with decreased inflammation and all-cause mortality in patients with chronic kidney disease. Kidney international 2012;81(3):300–306. doi:10.1038/ki.2011.355Evenepoel P, Bammens B, Verbeke K, Vanrenterghem Y. Acarbose treatment lowers generation and serum concentrations of the protein-bound solute p-cresol: a pilot study. Kidney international 2006;70(1):192–198. doi:10.1038/sj.ki.5001523Evenepoel P, Bammens B, Verbeke K, Vanrenterghem Y. Acarbose treatment lowers generation and serum concentrations of the protein-bound solute p-cresol: a pilot study. Kidney international 2006;70(1):192–198. doi:10.1038/sj.ki.5001523Лукичев БГ, Румянцев АШ, Панина ИЮ, Акименко В. Микробиота кишечника и хроническая болезнь почек. Сообщение второе. Нефрология 2019;23(1):18–31. doi:10.24884/1561-6274-2019-23-1-18-31Lukichev BG, Rumyantsev AS, Panina IYu, Akimenko V. Colonic microbiota and chronic kidney disease. Part II. Nephrology (SaintPetersburg) 2019;23(1):18–31 (In Russ.). doi:10.24884/1561-6274-2018-23-1-18-31Meijers B, De Preter V, Verbeke K et al. p-Cresyl sulfate serum concentrations in haemodialysis patients are reduced by the prebiotic oligofructose-enriched inulin. Nephrology, dialysis, transplantation 2010;25(1):219–224. doi:10.1093/ndt/gfp414Meijers B, De Preter V, Verbeke K et al. p-Cresyl sulfate serum concentrations in haemodialysis patients are reduced by the prebiotic oligofructose-enriched inulin. Nephrology, dialysis, transplantation 2010;25(1):219–224. doi:10.1093/ndt/gfp414Sueyoshi M, Fukunaga M, Mei M et al. Effects of lactulose on renal function and gut microbiota in adenine-induced chronic kidney disease rats. Clinical and experimental nephrology 2019;23(7):908–919. doi:10.1007/s10157-019-01727-4Sueyoshi M, Fukunaga M, Mei M et al. Effects of lactulose on renal function and gut microbiota in adenine-induced chronic kidney disease rats. Clinical and experimental nephrology 2019;23(7):908–919. doi:10.1007/s10157-019-01727-4Miyoshi M, Shiroto A, Kadoguchi H et al. Prebiotics Improved the Defecation Status via Changes in the Microbiota and Short-chain Fatty Acids in Hemodialysis Patients. Kobe J Med Sci 2020;66(1):E12–E21. PMID:32814753Miyoshi M, Shiroto A, Kadoguchi H et al. Prebiotics Improved the Defecation Status via Changes in the Microbiota and Short-chain Fatty Acids in Hemodialysis Patients. Kobe J Med Sci 2020;66(1):E12–E21. PMID:32814753Ramos C, Armani R, Canziani M et al. Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney disease patients: a randomized controlled trial. Nephrol Dial Transplant 2019;34(11):1876–1884. doi:10.1093/ndt/gfy171Ramos C, Armani R, Canziani M et al. Effect of prebiotic (fructooligosaccharide) on uremic toxins of chronic kidney disease patients: a randomized controlled trial. Nephrol Dial Transplant 2019;34(11):1876–1884. doi:10.1093/ndt/gfy171Ranganathan N, Ranganathan P, Friedman E et al. Pilot study of probiotic dietary supplementation for promoting healthy kidney function in patients with chronic kidney disease. Advances in therapy 2010;27(9):634–647. doi:10.1007/s12325-010-0059-9Ranganathan N, Ranganathan P, Friedman E et al. Pilot study of probiotic dietary supplementation for promoting healthy kidney function in patients with chronic kidney disease. Advances in therapy 2010;27(9):634–647. doi:10.1007/s12325-010-0059-9Natarajan R, Pechenyak B, Vyas U et al. Randomized controlled trial of strain-specific probiotic formulation (Renadyl) in dialysis patients. Biomed Res Int 2014;2014:568571. doi:10.1155/2014/568571Natarajan R, Pechenyak B, Vyas U et al. Randomized controlled trial of strain-specific probiotic formulation (Renadyl) in dialysis patients. Biomed Res Int 2014;2014:568571. doi:10.1155/2014/568571Taki K, Takayama F, Niwa T. Beneficial effects of Bifidobacteria in a gastroresistant seamless capsule on hyperhomocysteinemia in hemodialysis patients. Journal of renal nutrition 2005;15(1):77–80. doi:10.1053/j.jrn.2004.09.028Taki K, Takayama F, Niwa T. Beneficial effects of Bifidobacteria in a gastroresistant seamless capsule on hyperhomocysteinemia in hemodialysis patients. Journal of renal nutrition 2005;15(1):77–80. doi:10.1053/j.jrn.2004.09.028Guida B, Germanò R, Trio R et al. Effect of short-term synbiotic treatment on plasma p-cresol levels in patients with chronic renal failure: a randomized clinical trial. NMCD 2014;24(9):1043–1049. doi:10.1016/j.numecd.2014.04.007Guida B, Germanò R, Trio R et al. Effect of short-term synbiotic treatment on plasma p-cresol levels in patients with chronic renal failure: a randomized clinical trial. NMCD 2014;24(9):1043–1049. doi:10.1016/j.numecd.2014.04.007Rossi M, Johnson D, Morrison M et al. Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial. CJASN 2016;11(2):223–231. doi:10.2215/CJN.05240515Rossi M, Johnson D, Morrison M et al. Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial. CJASN 2016;11(2):223–231. doi:10.2215/CJN.05240515Cosola C, Rocchetti M, di Bari I et al. An Innovative Synbiotic Formulation Decreases Free Serum Indoxyl Sulfate, Small Intestine Permeability and Ameliorates Gastrointestinal Symptoms in a Randomized Pilot Trial in Stage IIIb-IV CKD Patients. Toxins (Basel) 2021;13(5):334. doi:10.3390/toxins13050334Cosola C, Rocchetti M, di Bari I et al. An Innovative Synbiotic Formulation Decreases Free Serum Indoxyl Sulfate, Small Intestine Permeability and Ameliorates Gastrointestinal Symptoms in a Randomized Pilot Trial in Stage IIIb-IV CKD Patients. Toxins (Basel) 2021;13(5):334. doi:10.3390/toxins13050334Marzocco S, Fazeli G, Di Micco L et al. Supplementation of Short-Chain Fatty Acid, Sodium Propionate, in Patients on Maintenance Hemodialysis: Beneficial Effects on Inflammatory Parameters and Gut-Derived Uremic Toxins, A Pilot Study (PLAN Study). J Clin Med 2018;7(10):315. doi:10.3390/jcm7100315Marzocco S, Fazeli G, Di Micco L et al. Supplementation of Short-Chain Fatty Acid, Sodium Propionate, in Patients on Maintenance Hemodialysis: Beneficial Effects on Inflammatory Parameters and Gut-Derived Uremic Toxins, A Pilot Study (PLAN Study). J Clin Med 2018;7(10):315. doi:10.3390/jcm7100315Miao W, Wu X, Wang K et al. Sodium Butyrate Promotes Reassembly of Tight Junctions in Caco-2 Monolayers Involving Inhibition of MLCK/MLC2 Pathway and Phosphorylation of PKCβ2. Int J Mol Sci 2016;17(10):1696. doi:10.3390/ijms17101696Miao W, Wu X, Wang K et al. Sodium Butyrate Promotes Reassembly of Tight Junctions in Caco-2 Monolayers Involving Inhibition of MLCK/MLC2 Pathway and Phosphorylation of PKCβ2. Int J Mol Sci 2016;17(10):1696. doi:10.3390/ijms17101696Andrade-Oliveira V, Amano M, Correa-Costa M et al. Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion. J Am Soc Nephrol 2015;26(8):1877–1888. doi:10.1681/ASN.2014030288Andrade-Oliveira V, Amano M, Correa-Costa M et al. Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion. J Am Soc Nephrol 2015;26(8):1877–1888. doi:10.1681/ASN.2014030288Ji C, Deng Y, Yang A et al. Improved Colon Mucosal Barrier Injury in 5/6 Nephrectomy Rats May Associate With Gut Microbiota Modification. Front Pharmacol 2020;11:1092. doi:10.3389/fphar.2020.01092Ji C, Deng Y, Yang A et al. Improved Colon Mucosal Barrier Injury in 5/6 Nephrectomy Rats May Associate With Gut Microbiota Modification. Front Pharmacol 2020;11:1092. doi:10.3389/fphar.2020.01092Zeng Y, Dai Z, Lu F et al. Emodin via colonic irrigation modulates gut microbiota and reduces uremic toxins in rats with chronic kidney disease. Oncotarget 2016;7(14):17468–17478. doi:10.18632/oncotarget.8160Zeng Y, Dai Z, Lu F et al. Emodin via colonic irrigation modulates gut microbiota and reduces uremic toxins in rats with chronic kidney disease. Oncotarget 2016;7(14):17468–17478. doi:10.18632/oncotarget.8160Mishima E, Fukuda S, Shima H et al. Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD. J Am Soc Nephrol 2015;26(8):1787–1794. doi:10.1681/ASN.2014060530Mishima E, Fukuda S, Shima H et al. Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD. J Am Soc Nephrol 2015;26(8):1787–1794. doi:10.1681/ASN.2014060530Schulman G, Agarwal R, Acharya M et al. A multicenter, randomized, double-blind, placebo-controlled, dose-ranging study of AST-120 (Kremezin) in patients with moderate to severe CKD. Am J Kidney Dis 2006;47(4):565–577. doi:10.1053/j.ajkd.2005.12.036Schulman G, Agarwal R, Acharya M et al. A multicenter, randomized, double-blind, placebo-controlled, dose-ranging study of AST-120 (Kremezin) in patients with moderate to severe CKD. Am J Kidney Dis 2006;47(4):565–577. doi:10.1053/j.ajkd.2005.12.036Niwa T, Ise M, Miyazaki T, Meada K. Suppressive effect of an oral sorbent on the accumulation of p-cresol in the serum of experimental uremic rats. Nephron 1993;65(1):82–87. doi:10.1159/000187446Niwa T, Ise M, Miyazaki T, Meada K. Suppressive effect of an oral sorbent on the accumulation of p-cresol in the serum of experimental uremic rats. Nephron 1993;65(1):82–87. doi:10.1159/000187446Yamagishi S, Nakamura K, Matsui T et al. Oral administration of AST-120 (Kremezin) is a promising therapeutic strategy for advanced glycation end product (AGE)-related disorders. Med Hypotheses 2007;69(3):666–668. doi:10.1016/j.mehy.2006.12.045Yamagishi S, Nakamura K, Matsui T et al. Oral administration of AST-120 (Kremezin) is a promising therapeutic strategy for advanced glycation end product (AGE)-related disorders. Med Hypotheses 2007;69(3):666–668. doi:10.1016/j.mehy.2006.12.045Vaziri N, Yuan J, Khazaeli M et al. Oral activated charcoal adsorbent (AST-120) ameliorates chronic kidney diseaseinduced intestinal epithelial barrier disruption. Am J Nephrol 2013;37(6):518–525. doi:10.1159/000351171Vaziri N, Yuan J, Khazaeli M et al. Oral activated charcoal adsorbent (AST-120) ameliorates chronic kidney diseaseinduced intestinal epithelial barrier disruption. Am J Nephrol 2013;37(6):518–525. doi:10.1159/000351171Chen Y, Wu M, Hu P et al. Effects and Safety of an Oral Adsorbent on Chronic Kidney Disease Progression: A Systematic Review and Meta-Analysis. Journal of clinical medicine 2019;8(10):1718. doi:10.3390/jcm8101718Chen Y, Wu M, Hu P et al. Effects and Safety of an Oral Adsorbent on Chronic Kidney Disease Progression: A Systematic Review and Meta-Analysis. Journal of clinical medicine 2019;8(10):1718. doi:10.3390/jcm8101718Perianayagam M, Jaber B. Endotoxin-binding affinity of sevelamer hydrochloride. Am J Nephrol 2008;28(5):802–807. doi:10.1159/000135691Perianayagam M, Jaber B. Endotoxin-binding affinity of sevelamer hydrochloride. Am J Nephrol 2008;28(5):802–807. doi:10.1159/000135691Navarro-González J, Mora-Fernández C, Muros de Fuentes M et al. Effect of phosphate binders on serum inflammatory profile, soluble CD14, and endotoxin levels in hemodialysis patients. Clin J Am Soc Nephrol 2011;6(9):2272–2279. doi:10.2215/CJN.01650211Navarro-González J, Mora-Fernández C, Muros de Fuentes M et al. Effect of phosphate binders on serum inflammatory profile, soluble CD14, and endotoxin levels in hemodialysis patients. Clin J Am Soc Nephrol 2011;6(9):2272–2279. doi:10.2215/CJN.01650211Luo F, Patel K, Marquez I et al. Effect of increasing dialyzer mass transfer area coefficient and dialysate flow on clearance of protein-bound solutes: a pilot crossover trial. American journal of kidney diseases 2009;53(6):1042–1049. doi:10.1053/j.ajkd.2009.01.265Luo F, Patel K, Marquez I et al. Effect of increasing dialyzer mass transfer area coefficient and dialysate flow on clearance of protein-bound solutes: a pilot crossover trial. American journal of kidney diseases 2009;53(6):1042–1049. doi:10.1053/j.ajkd.2009.01.265Meyer T, Peattie J, Miller J et al. Increasing the clearance of protein-bound solutes by addition of a sorbent to the dialysate. JASN 2007;18(3):868–874. doi:10.1681/ASN.2006080863Meyer T, Peattie J, Miller J et al. Increasing the clearance of protein-bound solutes by addition of a sorbent to the dialysate. JASN 2007;18(3):868–874. doi:10.1681/ASN.2006080863Vanholder R, Meert N, Van Biesen W et al. Why do patients on peritoneal dialysis have low blood levels of protein-bound solutes?. Nature clinical practice. Nephrology 2009;5(3):130–131. doi:10.1038/ncpneph1023Vanholder R, Meert N, Van Biesen W et al. Why do patients on peritoneal dialysis have low blood levels of protein-bound solutes?. Nature clinical practice. Nephrology 2009;5(3):130–131. doi:10.1038/ncpneph1023

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