{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T02:06:39Z","timestamp":1793239599119,"version":"4.5.0"},"reference-count":170,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T00:00:00Z","timestamp":1617148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Numerous studies have indicated that the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) is strictly associated with the accumulation of toxic metabolites in blood and other metabolic compartments. This accumulation was suggested to be related to enhanced generation of toxins from the dysbiotic microbiome accompanied by their reduced elimination by impaired kidneys. Intestinal microbiota play a key role in the accumulation of uremic toxins due to the fact that numerous uremic solutes are generated in the process of protein fermentation by colonic microbiota. Some disease states, including CKD, are associated with the presence of dysbiosis, which can be defined as an \u201cimbalanced intestinal microbial community with quantitative and qualitative changes in the composition and metabolic activities of the gut microbiota\u201d. The results of studies have confirmed the altered composition and functions of gut microbial community in chronic kidney disease. In the course of CKD protein-bound uremic toxins, including indoxyl sulfate, p-cresyl glucuronide, p-cresyl sulfate and indole-3-acetic acid are progressively accumulated. The presence of chronic kidney disease may be accompanied by the development of intestinal inflammation and epithelial barrier impairment leading to hastened systemic translocation of bacterial-derived uremic toxins and consequent oxidative stress injury to the kidney, cardiovascular and endocrine systems. These findings offer new therapeutic possibilities for the management of uremia, inflammation and kidney disease progression and the prevention of adverse outcomes in CKD patients. It seems that dietary interventions comprising prebiotics, probiotics, and synbiotics could pose a promising strategy in the management of uremic toxins in CKD.<\/jats:p>","DOI":"10.3390\/toxins13040252","type":"journal-article","created":{"date-parts":[[2021,3,31]],"date-time":"2021-03-31T10:24:33Z","timestamp":1617186273000},"page":"252","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":309,"title":["The Impact of CKD on Uremic Toxins and Gut Microbiota"],"prefix":"10.3390","volume":"13","author":[{"given":"Jacek","family":"Rysz","sequence":"first","affiliation":[{"name":"Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Franczyk","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janusz","family":"\u0141awi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Urology, Institute of Medical Sciences, Medical College of Rzeszow University, 35-055 Rzeszow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Olszewski","sequence":"additional","affiliation":[{"name":"Department of Gerontology, Public Health and Didactics, Rheumatology and Rehabilitation, National Institute of Geriatrics, 02-637 Warsaw, Poland"},{"name":"Department of Ultrasound, Institute of Fundamental Technological Research, Polish Academy of Sciences, 02-637 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksanda","family":"Cia\u0142kowska-Rysz","sequence":"additional","affiliation":[{"name":"Palliative Medicine Unit, Department of Oncology, Medical University of Lodz, 90-549 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3322-5655","authenticated-orcid":false,"given":"Anna","family":"Gluba-Brz\u00f3zka","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1053\/j.ajkd.2015.09.027","article-title":"Role of the Gut Microbiome in Uremia: A Potential Therapeutic Target","volume":"67","author":"Ramezani","year":"2016","journal-title":"Am. J. Kidney Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1681\/ASN.2013080905","article-title":"The Gut Microbiome, Kidney Disease, and Targeted Interventions","volume":"25","author":"Ramezani","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.semnephrol.2018.01.008","article-title":"Contributory Role of Gut Microbiota and Their Metabolites toward Cardiovascular Complications in Chronic Kidney Disease","volume":"38","author":"Li","year":"2018","journal-title":"Semin. Nephrol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12967-018-1756-4","article-title":"Microbiome\u2013metabolome reveals the contribution of gut\u2013kidney axis on kidney disease","volume":"17","author":"Chen","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/ki.2012.345","article-title":"Chronic kidney disease alters intestinal microbial flora","volume":"83","author":"Vaziri","year":"2013","journal-title":"Kidney Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1159\/000360010","article-title":"Expansion of urease- and uricase-containing, indole- and p-cresol-forming and contraction of short-chain fatty acid-producing intestinal microbiota in ESRD","volume":"39","author":"Wong","year":"2014","journal-title":"Am. J. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1159\/000189334","article-title":"Inhibition of the accumulation of uremic toxins in the blood and their precursors in the feces after oral administration of Lebenin, a lactic acid bacteria preparation, to uremic patients undergoing hemodialysis","volume":"74","author":"Hida","year":"1996","journal-title":"Nephron"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1056\/NEJMra071313","article-title":"Uremia","volume":"357","author":"Meyer","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.2215\/CJN.03980609","article-title":"Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients","volume":"4","author":"Barreto","year":"2009","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1136\/gutjnl-2019-319766","article-title":"Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents","volume":"69","author":"Wang","year":"2020","journal-title":"Gut"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.kint.2017.02.011","article-title":"Evaluation of the impact of gut microbiota on uremic solute accumulation by a CE-TOFMS-based metabolomics approach","volume":"92","author":"Mishima","year":"2017","journal-title":"Kidney Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/BF01307542","article-title":"The gastrointestinal tract in uremia","volume":"38","author":"Kang","year":"1993","journal-title":"Dig. Dis. Sci."},{"key":"ref_13","first-page":"608","article-title":"Pathology of gastrointestinal tract in chronic hemodialysis patients: An autopsy study of 78 cases","volume":"80","author":"Vaziri","year":"1985","journal-title":"Am. J. Gastroenterol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1172\/JCI103940","article-title":"Urea metabolism in man","volume":"38","author":"Walser","year":"1959","journal-title":"J. Clin. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1079\/NRR200498","article-title":"Urea nitrogen salvage mechanisms and their relevance to ruminants, non-ruminants and man","volume":"18","author":"Stewart","year":"2005","journal-title":"Nutr. Res. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1042\/cs0860511","article-title":"Enhanced enteric excretion of urate in rats with chronic renal failure","volume":"86","author":"Hatch","year":"1994","journal-title":"Clin. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1136\/gut.32.7.754","article-title":"Impaired intestinal barrier function measured by differently sized polyethylene glycols in patients with chronic renal failure","volume":"32","author":"Magnusson","year":"1991","journal-title":"Gut"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1159\/000343886","article-title":"Uremic plasma impairs barrier function and depletes the tight junction protein constituents of intestinal epithelium","volume":"36","author":"Vaziri","year":"2012","journal-title":"Am. J. Nephrol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000345969","article-title":"Role of urea in intestinal barrier dysfunction and disruption of epithelial tight junction in chronic kidney disease","volume":"37","author":"Vaziri","year":"2013","journal-title":"Am. J. Nephrol."},{"key":"ref_20","first-page":"9","article-title":"Gut microbiota in chronic kidney disease","volume":"37","author":"Guldris","year":"2017","journal-title":"Nefrolog\u00eda"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1159\/000321848","article-title":"Intestinal-renal syndrome: Mirage or reality?","volume":"31","author":"Ritz","year":"2011","journal-title":"Blood Purif."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1093\/ndt\/gfu287","article-title":"Alterations of intestinal barrier and microbiota in chronic kidney disease","volume":"30","author":"Sabatino","year":"2014","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1007\/s00240-003-0381-7","article-title":"Bacterial translocation in experimental uremia","volume":"32","author":"Nascimento","year":"2004","journal-title":"Urol. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1097\/00075197-200211000-00012","article-title":"Intestinal barrier function","volume":"5","author":"Baumgart","year":"2002","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1159\/000353764","article-title":"Chronic kidney disease causes disruption of gastric and small intestinal epithelial tight junction","volume":"38","author":"Vaziri","year":"2013","journal-title":"Am. J. Nephrol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3216","DOI":"10.1099\/mic.0.040618-0","article-title":"Long-term impacts of antibiotic exposure on the human intestinal microbiota","volume":"156","author":"Jernberg","year":"2010","journal-title":"Microbiology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1053\/j.ajkd.2004.04.048","article-title":"Colonic transit time in long-term dialysis patients","volume":"44","author":"Wu","year":"2004","journal-title":"Am. J. Kidney Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.chom.2016.10.021","article-title":"Modulation of a Circulating Uremic Solute via Rational Genetic Manipulation of the Gut Microbiota","volume":"20","author":"Devlin","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nature08821","article-title":"A human gut microbial gene catalogue established by metagenomic sequencing","volume":"464","author":"Qin","year":"2010","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Gevers, D., Knight, R., Petrosino, J.F., Huang, K., McGuire, A.L., Birren, B.W., Nelson, K.E., White, O., Meth\u00e9, B.A., and Huttenhower, C. (2012). The Human Microbiome Project: A community resource for the healthy human microbiome. PLoS Biol., 10.","DOI":"10.1371\/journal.pbio.1001377"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10452","DOI":"10.1073\/pnas.1734063100","article-title":"Honor thy symbionts","volume":"100","author":"Xu","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1126\/science.1110591","article-title":"Diversity of the human intestinal microbial flora","volume":"308","author":"Eckburg","year":"2005","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/nature11552","article-title":"Functional interactions between the gut microbiota and host metabolism","volume":"489","author":"Tremaroli","year":"2012","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrgastro.2016.169","article-title":"The intestinal epithelial barrier: A therapeutic target?","volume":"14","author":"Odenwald","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"769","DOI":"10.3945\/jn.110.135657","article-title":"Regulation of tight junction permeability by intestinal bacteria and dietary components","volume":"141","author":"Ulluwishewa","year":"2011","journal-title":"J. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1053\/j.gastro.2007.02.056","article-title":"Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function","volume":"132","author":"Cario","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1097\/00008469-199703001-00009","article-title":"Intestinal flora and endogenous vitamin synthesis","volume":"6","author":"Hill","year":"1997","journal-title":"Eur. J. Cancer Prev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/j.1574-6976.1998.tb00382.x","article-title":"Biotransformation of monoterpenes, bile acids, and other isoprenoids in anaerobic ecosystems","volume":"22","author":"Hylemon","year":"1998","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3841","DOI":"10.1128\/AEM.68.8.3841-3847.2002","article-title":"Oxalobacter formigenes and Its Potential Role in Human Health","volume":"68","author":"Duncan","year":"2002","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1177\/0148607197021006357","article-title":"Role of intestinal bacteria in nutrient metabolism","volume":"21","author":"Cummings","year":"1997","journal-title":"JPEN J. Parenter. Enter. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"751s","DOI":"10.1093\/jn\/137.3.751S","article-title":"Metabolic diversity of the intestinal microbiota: Implications for health and disease","volume":"137","author":"Blaut","year":"2007","journal-title":"J. Nutr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"C1018","DOI":"10.1152\/ajpcell.00131.2005","article-title":"Soluble factors from Lactobacillus GG activate MAPKs and induce cytoprotective heat shock proteins in intestinal epithelial cells","volume":"290","author":"Tao","year":"2006","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"G1025","DOI":"10.1152\/ajpgi.90227.2008","article-title":"Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function","volume":"295","author":"Ewaschuk","year":"2008","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1007\/s00383-002-0855-7","article-title":"Probiotics up-regulate MUC-2 mucin gene expression in a Caco-2 cell-culture model","volume":"18","author":"Mattar","year":"2002","journal-title":"Pediatr. Surg. Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1111\/j.1365-2249.2007.03587.x","article-title":"Probiotic lactobacilli and VSL#3 induce enterocyte beta-defensin 2","volume":"151","author":"Schlee","year":"2008","journal-title":"Clin. Exp. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.cell.2004.07.002","article-title":"Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis","volume":"118","author":"Paglino","year":"2004","journal-title":"Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.trsl.2012.10.007","article-title":"Short chain fatty acids and their receptors: New metabolic targets","volume":"161","author":"Layden","year":"2013","journal-title":"Transl. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1681\/ASN.2014030288","article-title":"Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion","volume":"26","author":"Amano","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1681\/ASN.2014111157","article-title":"Gut Feeling in AKI: The Long Arm of Short-Chain Fatty Acids","volume":"26","author":"Barrows","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s41110-017-0054-x","article-title":"The cross-talk between the kidney and the gut: Implications for chronic kidney disease","volume":"42","author":"Ramos","year":"2017","journal-title":"Nutrire"},{"key":"ref_51","first-page":"92","article-title":"Biomodulation of the toxic and nutritional effects of small bowel bacterial overgrowth in end-stage kidney disease using freeze-dried Lactobacillus acidophilus","volume":"22","author":"Simenhoff","year":"1996","journal-title":"Min. Electrolyte Metab."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4781","DOI":"10.1021\/pr300581s","article-title":"Metabolomics view on gut microbiome modulation by polyphenol-rich foods","volume":"11","author":"Moco","year":"2012","journal-title":"J. Proteome Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"427","DOI":"10.4056\/sigs.3336746","article-title":"Non contiguous-finished genome sequence and description of Alistipes obesi sp. nov","volume":"7","author":"Hugon","year":"2013","journal-title":"Stand. Genom. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1099\/jmm.0.47744-0","article-title":"Assessing the role of p-cresol tolerance in Clostridium difficile","volume":"57","author":"Dawson","year":"2008","journal-title":"J. Med. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1093\/ndt\/gfq624","article-title":"Effects of synbiotic treatment on serum level of p-cresol in haemodialysis patients: A preliminary study","volume":"26","author":"Nakabayashi","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1136\/gutjnl-2018-317561","article-title":"Gut microbiota dynamics and uraemic toxins: One size does not fit all","volume":"68","author":"Joossens","year":"2019","journal-title":"Gut"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1681\/ASN.2015030279","article-title":"The Influence of CKD on Colonic Microbial Metabolism","volume":"27","author":"Poesen","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1016\/j.kint.2020.01.028","article-title":"Gut microbiota generation of protein-bound uremic toxins and related metabolites is not altered at different stages of chronic kidney disease","volume":"97","author":"Gryp","year":"2020","journal-title":"Kidney Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1046\/j.1523-1755.2003.00314.x","article-title":"Evidence for impaired assimilation of protein in chronic renal failure","volume":"64","author":"Bammens","year":"2003","journal-title":"Kidney Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/ki.2011.355","article-title":"High dietary fiber intake is associated with decreased inflammation and all-cause mortality in patients with chronic kidney disease","volume":"81","author":"Krishnamurthy","year":"2012","journal-title":"Kidney Int."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1146\/annurev.micro.58.030603.123811","article-title":"Bacterial iron sources: From siderophores to hemophores","volume":"58","author":"Wandersman","year":"2004","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1046\/j.1523-1755.1998.00812.x","article-title":"Factors predicting malnutrition in hemodialysis patients: A cross-sectional study","volume":"53","author":"Qureshi","year":"1998","journal-title":"Kidney Int."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1002\/art.1780080429","article-title":"Role of the intestinal tract in the elimination of uric acid","volume":"8","author":"Sorensen","year":"1965","journal-title":"Arthritis Rheumatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1093\/ndt\/gfv095","article-title":"Altered intestinal microbial flora and impaired epithelial barrier structure and function in CKD: The nature, mechanisms, consequences and potential treatment","volume":"31","author":"Vaziri","year":"2016","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1007\/s11255-018-1873-2","article-title":"The crosstalk of gut microbiota and chronic kidney disease: Role of inflammation, proteinuria, hypertension, and diabetes mellitus","volume":"50","author":"Kanbay","year":"2018","journal-title":"Int. Urol. Nephrol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e111","DOI":"10.1159\/000074327","article-title":"Uremic toxins overload accelerates renal damage in a rat model of chronic renal failure","volume":"95","author":"Satoh","year":"2003","journal-title":"Nephron Exp. Nephrol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/sj.bjp.0704482","article-title":"Uraemic toxins induce proximal tubular injury via organic anion transporter 1-mediated uptake","volume":"135","author":"Motojima","year":"2002","journal-title":"Br. J. Pharm."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/j.1523-1755.2004.00399.x","article-title":"The uremic solutes p-cresol and indoxyl sulfate inhibit endothelial proliferation and wound repair","volume":"65","author":"Dou","year":"2004","journal-title":"Kidney Int."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1093\/ndt\/gfl584","article-title":"P-cresylsulphate, the main in vivo metabolite of p-cresol, activates leucocyte free radical production","volume":"22","author":"Schepers","year":"2007","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Adesso, S., Popolo, A., Bianco, G., Sorrentino, R., Pinto, A., Autore, G., and Marzocco, S. (2013). The uremic toxin indoxyl sulphate enhances macrophage response to LPS. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076778"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1128\/aem.55.3.679-683.1989","article-title":"Significance of microflora in proteolysis in the colon","volume":"55","author":"Gibson","year":"1989","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/j.numecd.2014.04.006","article-title":"Uraemic toxins and cardiovascular disease across the chronic kidney disease spectrum: An observational study","volume":"24","author":"Rossi","year":"2014","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1093\/ndt\/gfq580","article-title":"p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease","volume":"26","author":"Wu","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1093\/ndt\/gfp592","article-title":"Free p-cresylsulphate is a predictor of mortality in patients at different stages of chronic kidney disease","volume":"25","author":"Liabeuf","year":"2010","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Liabeuf, S., Glorieux, G., Lenglet, A., Diouf, M., Schepers, E., Desjardins, L., Choukroun, G., Vanholder, R., and Massy, Z.A. (2013). Does p-cresylglucuronide have the same impact on mortality as other protein-bound uremic toxins?. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067168"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1038\/sj.ki.5000115","article-title":"Free serum concentrations of the protein-bound retention solute p-cresol predict mortality in hemodialysis patients","volume":"69","author":"Bammens","year":"2006","journal-title":"Kidney Int."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1681\/ASN.2013121283","article-title":"The cardiovascular effect of the uremic solute indole-3 acetic acid","volume":"26","author":"Dou","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"662","DOI":"10.5114\/aoms.2013.36901","article-title":"Serum p-cresyl sulfate predicts cardiovascular disease and mortality in elderly hemodialysis patients","volume":"9","author":"Lin","year":"2013","journal-title":"Arch. Med. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1681\/ASN.2011121175","article-title":"Normal and pathologic concentrations of uremic toxins","volume":"23","author":"Duranton","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Vanholder, R., Glorieux, G., De Smet, R., and Lameire, N. (2003). New insights in uremic toxins. Kidney Int. Suppl., S6\u2013S10.","DOI":"10.1046\/j.1523-1755.63.s84.43.x"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Gryp, T., Vanholder, R., Vaneechoutte, M., and Glorieux, G. (2017). p-Cresyl Sulfate. Toxins, 9.","DOI":"10.3390\/toxins9020052"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.2215\/CJN.03150318","article-title":"Characteristics of Colon-Derived Uremic Solutes","volume":"13","author":"Mair","year":"2018","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1046\/j.1523-1755.2003.00924.x","article-title":"Review on uremic toxins: Classification, concentration, and interindividual variability","volume":"63","author":"Vanholder","year":"2003","journal-title":"Kidney Int."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1373\/clinchem.2005.050781","article-title":"Gas chromatographic-mass spectrometric analysis for measurement of p-cresol and its conjugated metabolites in uremic and normal serum","volume":"51","author":"Bammens","year":"2005","journal-title":"Clin. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1002\/jcla.20456","article-title":"p-Cresylsulfate and indoxyl sulfate level at different stages of chronic kidney disease","volume":"25","author":"Lin","year":"2011","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.2215\/CJN.02440314","article-title":"Handling of Drugs, Metabolites, and Uremic Toxins by Kidney Proximal Tubule Drug Transporters","volume":"10","author":"Nigam","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Fujii, H., Goto, S., and Fukagawa, M. (2018). Role of Uremic Toxins for Kidney, Cardiovascular, and Bone Dysfunction. Toxins, 10.","DOI":"10.3390\/toxins10050202"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1046\/j.1523-1755.2003.00906.x","article-title":"Uremic toxins of organic anions up-regulate PAI-1 expression by induction of NF-kappaB and free radical in proximal tubular cells","volume":"63","author":"Motojima","year":"2003","journal-title":"Kidney Int."},{"key":"ref_89","first-page":"33","article-title":"Glomerular Filtration Barrier Assembly: An insight","volume":"1","author":"Arif","year":"2013","journal-title":"Postdoc J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1056\/NEJM197804132981507","article-title":"Molecular basis of proteinuria of glomerular origin","volume":"298","author":"Brenner","year":"1978","journal-title":"N. Engl. J. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.tcb.2007.06.006","article-title":"Actin up: Regulation of podocyte structure and function by components of the actin cytoskeleton","volume":"17","author":"Faul","year":"2007","journal-title":"Trends Cell Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1083\/jcb.111.3.1255","article-title":"The tight junction protein ZO-1 is concentrated along slit diaphragms of the glomerular epithelium","volume":"111","author":"Schnabel","year":"1990","journal-title":"J. Cell Biol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.1681\/ASN.2014121193","article-title":"Tubular Secretion in CKD","volume":"27","author":"Laha","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.semnephrol.2014.02.010","article-title":"The kidney and uremic toxin removal: Glomerulus or tubule?","volume":"34","author":"Masereeuw","year":"2014","journal-title":"Semin. Nephrol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.2215\/CJN.02940509","article-title":"p-Cresyl sulfate and indoxyl sulfate in hemodialysis patients","volume":"4","author":"Meijers","year":"2009","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_96","first-page":"CD005016","article-title":"High-flux versus low-flux membranes for end-stage kidney disease","volume":"2012","author":"Palmer","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s41100-016-0056-9","article-title":"Removal of uremic toxins by renal replacement therapies: A review of current progress and future perspectives","volume":"2","author":"Yamamoto","year":"2016","journal-title":"Ren. Replace. Ther."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1007\/s00216-012-5929-3","article-title":"Protein-bound uremic toxins in hemodialysis patients measured by liquid chromatography\/tandem mass spectrometry and their effects on endothelial ROS production","volume":"403","author":"Itoh","year":"2012","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1111\/j.1574-6976.2009.00204.x","article-title":"Indole as an intercellular signal in microbial communities","volume":"34","author":"Lee","year":"2010","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/s13073-016-0296-x","article-title":"Microbial metabolism of dietary components to bioactive metabolites: Opportunities for new therapeutic interventions","volume":"8","author":"Zhang","year":"2016","journal-title":"Genome Med."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Shimada, Y., Kinoshita, M., Harada, K., Mizutani, M., Masahata, K., Kayama, H., and Takeda, K. (2013). Commensal bacteria-dependent indole production enhances epithelial barrier function in the colon. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0080604"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1093\/ndt\/gfm065","article-title":"Effect of the super-flux cellulose triacetate dialyser membrane on the removal of non-protein-bound and protein-bound uraemic solutes","volume":"22","author":"Dhondt","year":"2007","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_103","first-page":"598","article-title":"The influence of dialysis treatment modality on the decline of remaining renal function","volume":"37","author":"Lysaght","year":"1991","journal-title":"ASAIO Trans."},{"key":"ref_104","first-page":"S15","article-title":"Indoxyl sulfate increases the gene expressions of TGF-beta 1, TIMP-1 and pro-alpha 1(I) collagen in uremic rat kidneys","volume":"62","author":"Miyazaki","year":"1997","journal-title":"Kidney Int. Suppl."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1038\/sj.ki.5000340","article-title":"Indoxyl sulfate stimulates proliferation of rat vascular smooth muscle cells","volume":"69","author":"Yamamoto","year":"2006","journal-title":"Kidney Int."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1111\/j.1538-7836.2007.02540.x","article-title":"The uremic solute indoxyl sulfate induces oxidative stress in endothelial cells","volume":"5","author":"Dou","year":"2007","journal-title":"J. Thromb. Haemost."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.atherosclerosis.2012.07.012","article-title":"The role of protein-bound uremic toxins on peripheral artery disease and vascular access failure in patients on hemodialysis","volume":"225","author":"Lin","year":"2012","journal-title":"Atherosclerosis"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1771","DOI":"10.1093\/eurheartj\/ehp574","article-title":"Does indoxyl sulfate, a uraemic toxin, have direct effects on cardiac fibroblasts and myocytes?","volume":"31","author":"Lekawanvijit","year":"2010","journal-title":"Eur. Heart J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"e002023","DOI":"10.1161\/JAHA.115.002023","article-title":"Role of Indoxyl Sulfate as a Predisposing Factor for Atrial Fibrillation in Renal Dysfunction","volume":"4","author":"Aoki","year":"2015","journal-title":"J. Am. Heart Assoc."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2176","DOI":"10.1093\/ndt\/gfr647","article-title":"Indoxyl sulphate inhibits osteoclast differentiation and function","volume":"27","author":"Mozar","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"289","DOI":"10.5935\/0101-2800.20140042","article-title":"Association between indoxyl sulfate and bone histomorphometry in pre-dialysis chronic kidney disease patients","volume":"36","author":"Barreto","year":"2014","journal-title":"J. Bras. Nefrol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/sj.ki.5002097","article-title":"Indoxyl sulfate induces skeletal resistance to parathyroid hormone in cultured osteoblastic cells","volume":"71","author":"Iwasaki","year":"2007","journal-title":"Kidney Int."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1097\/MAJ.0b013e3182989f26","article-title":"Association of Indoxyl Sulfate with Fibroblast Growth Factor 23 in Patients with Advanced Chronic Kidney Disease","volume":"347","author":"Lin","year":"2014","journal-title":"Am. J. Med. Sci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1038\/labinvest.2011.114","article-title":"Indoxyl sulfate, a representative uremic toxin, suppresses erythropoietin production in a HIF-dependent manner","volume":"91","author":"Chiang","year":"2011","journal-title":"Lab. Investig."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1053\/j.jrn.2014.10.011","article-title":"Role of Uremic Toxins in Erythropoiesis-Stimulating Agent Resistance in Chronic Kidney Disease and Dialysis Patients","volume":"25","author":"Nangaku","year":"2015","journal-title":"J. Ren. Nutr."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Ahmed, M.S.E., Abed, M., Voelkl, J., and Lang, F. (2013). Triggering of suicidal erythrocyte death by uremic toxin indoxyl sulfate. BMC Nephrol., 14.","DOI":"10.1186\/1471-2369-14-244"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1016\/S0140-6736(83)92478-9","article-title":"Fermentation in the human large intestine: Evidence and implications for health","volume":"1","author":"Cummings","year":"1983","journal-title":"Lancet"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1093\/ndt\/gfq818","article-title":"The gut-kidney axis: Indoxyl sulfate, p-cresyl sulfate and CKD progression","volume":"26","author":"Meijers","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"4149","DOI":"10.1093\/ndt\/gfr562","article-title":"Basolateral transport of the uraemic toxin p-cresyl sulfate: Role for organic anion transporters?","volume":"26","author":"Mutsaers","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.2215\/CJN.00300113","article-title":"Renal clearance and intestinal generation of p-cresyl sulfate and indoxyl sulfate in CKD","volume":"8","author":"Poesen","year":"2013","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1038\/ki.2008.31","article-title":"Free p-cresol is associated with cardiovascular disease in hemodialysis patients","volume":"73","author":"Meijers","year":"2008","journal-title":"Kidney Int."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Sun, C.Y., Chang, S.C., and Wu, M.S. (2012). Uremic toxins induce kidney fibrosis by activating intrarenal renin-angiotensin-aldosterone system associated epithelial-to-mesenchymal transition. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0034026"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/ki.2012.448","article-title":"p-Cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase","volume":"83","author":"Watanabe","year":"2013","journal-title":"Kidney Int."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.2215\/CJN.07971109","article-title":"p-Cresol and cardiovascular risk in mild-to-moderate kidney disease","volume":"5","author":"Meijers","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"36618","DOI":"10.1038\/srep36618","article-title":"Metabolic alterations by indoxyl sulfate in skeletal muscle induce uremic sarcopenia in chronic kidney disease","volume":"6","author":"Sato","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1681\/ASN.2013101062","article-title":"The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: A systematic review","volume":"25","author":"Vanholder","year":"2014","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"F824","DOI":"10.1152\/ajprenal.00314.2017","article-title":"Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model","volume":"315","author":"Mishima","year":"2018","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1093\/ndt\/gfr453","article-title":"Serum free p-cresyl sulfate levels predict cardiovascular and all-cause mortality in elderly hemodialysis patients--a prospective cohort study","volume":"27","author":"Wu","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.arcmed.2014.04.002","article-title":"Protein-bound uremic toxins, inflammation and oxidative stress: A cross-sectional study in stage 3-4 chronic kidney disease","volume":"45","author":"Rossi","year":"2014","journal-title":"Arch. Med. Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"2779","DOI":"10.1007\/s00204-015-1652-0","article-title":"Indoxyl sulfate enhances IL-1\u03b2-induced E-selectin expression in endothelial cells in acute kidney injury by the ROS\/MAPKs\/NF\u03baB\/AP-1 pathway","volume":"90","author":"Shen","year":"2016","journal-title":"Arch. Toxicol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s40620-019-00589-z","article-title":"The role of the intestinal microbiota in uremic solute accumulation: A focus on sulfur compounds","volume":"32","author":"Perna","year":"2019","journal-title":"J. Nephrol."},{"key":"ref_132","first-page":"124","article-title":"Identification and determination of phenylacetylglutamine, a major nitrogenous metabolite in plasma of uremic patients","volume":"32","author":"Zimmerman","year":"1989","journal-title":"Clin. Nephrol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1016\/j.cell.2015.11.055","article-title":"Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis","volume":"163","author":"Wang","year":"2015","journal-title":"Cell"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1146\/annurev-nutr-071816-064732","article-title":"Trimethylamine N-Oxide, the Microbiome, and Heart and Kidney Disease","volume":"37","author":"Zeisel","year":"2017","journal-title":"Annu. Rev. Nutr."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1056\/NEJMoa1109400","article-title":"Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk","volume":"368","author":"Tang","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1161\/CIRCRESAHA.116.305360","article-title":"Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease","volume":"116","author":"Tang","year":"2015","journal-title":"Circ. Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/nm.3145","article-title":"Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis","volume":"19","author":"Koeth","year":"2013","journal-title":"Nat. Med."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature09922","article-title":"Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease","volume":"472","author":"Wang","year":"2011","journal-title":"Nature"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1681\/ASN.2014111063","article-title":"Serum Trimethylamine-N-Oxide is Elevated in CKD and Correlates with Coronary Atherosclerosis Burden","volume":"27","author":"Stubbs","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Missailidis, C., H\u00e4llqvist, J., Qureshi, A.R., Barany, P., Heimb\u00fcrger, O., Lindholm, B., Stenvinkel, P., and Bergman, P. (2016). Serum Trimethylamine-N-Oxide Is Strongly Related to Renal Function and Predicts Outcome in Chronic Kidney Disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0141738"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1046\/j.1525-139X.2001.00072.x","article-title":"Uremic toxicity: Urea and beyond","volume":"14","author":"Depner","year":"2001","journal-title":"Semin. Dial."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/sdi.12381","article-title":"The Chronic Kidney Disease\u2014Colonic Axis","volume":"28","author":"Pahl","year":"2015","journal-title":"Semin. Dial."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s11906-017-0727-0","article-title":"Gut Microbiome in Chronic Kidney Disease","volume":"19","author":"Armani","year":"2017","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2094","DOI":"10.1093\/ajcn\/32.10.2094","article-title":"The effect of meat protein and dietary fiber on colonic function and metabolism. II. Bacterial metabolites in feces and urine","volume":"32","author":"Cummings","year":"1979","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Poesen, R., Mutsaers, H.A., Windey, K., van den Broek, P.H., Verweij, V., Augustijns, P., Kuypers, D., Jansen, J., Evenepoel, P., and Verbeke, K. (2015). The Influence of Dietary Protein Intake on Mammalian Tryptophan and Phenolic Metabolites. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0140820"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"982","DOI":"10.2215\/CJN.12491211","article-title":"The production of p-cresol sulfate and indoxyl sulfate in vegetarians versus omnivores","volume":"7","author":"Patel","year":"2012","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.2215\/CJN.00490114","article-title":"Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients","volume":"9","author":"Sirich","year":"2014","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1016\/j.numecd.2014.04.007","article-title":"Effect of short-term synbiotic treatment on plasma p-cresol levels in patients with chronic renal failure: A randomized clinical trial","volume":"24","author":"Guida","year":"2014","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Poesen, R., Evenepoel, P., de Loor, H., Delcour, J.A., Courtin, C.M., Kuypers, D., Augustijns, P., Verbeke, K., and Meijers, B. (2016). The Influence of Prebiotic Arabinoxylan Oligosaccharides on Microbiota Derived Uremic Retention Solutes in Patients with Chronic Kidney Disease: A Randomized Controlled Trial. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0153893"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1093\/ndt\/gfp414","article-title":"p-Cresyl sulfate serum concentrations in haemodialysis patients are reduced by the prebiotic oligofructose-enriched inulin","volume":"25","author":"Meijers","year":"2010","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_151","unstructured":"FAO, and WHO (2006). Probiotics in Food: Health and Nutritional Properties and Guidelines for Evaluation: Report of a Joint FAO\/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food including Powder Milk with Live Lactic Acid Bacteria, Cordoba, Argentina, 1\u20134 October 2001 [and] Report of a Joint FAO\/WHO Working Group on Drafting Guidelines for the Evaluation of Probiotics in Food, London, Ontario, Canada, 30 April\u20131 May 2002, Food and Agriculture Organization of the United Nations and World Health Organization."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.femsec.2005.01.003","article-title":"Modulation of the microbial ecology of the human colon by probiotics, prebiotics and synbiotics to enhance human health: An overview of enabling science and potential applications","volume":"52","author":"Rastall","year":"2005","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1073\/pnas.0809919106","article-title":"Differential NF-\u03baB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance","volume":"106","author":"Troost","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"S142","DOI":"10.1053\/ajkd.2003.50104","article-title":"Bifidobacterium in gastro-resistant seamless capsule reduces serum levels of indoxyl sulfate in patients on hemodialysis","volume":"41","author":"Takayama","year":"2003","journal-title":"Am. J. Kidney Dis."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"423","DOI":"10.3920\/BM2014.0088","article-title":"The effect of probiotics on serum levels of cytokine and endotoxin in peritoneal dialysis patients: A randomised, double-blind, placebo-controlled trial","volume":"6","author":"Wang","year":"2015","journal-title":"Benef. Microbes"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.copbio.2015.09.001","article-title":"Prebiotics: Why definitions matter","volume":"37","author":"Hutkins","year":"2016","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/ejcn.2014.237","article-title":"Dietary fiber effects in chronic kidney disease: A systematic review and meta-analysis of controlled feeding trials","volume":"69","author":"Chiavaroli","year":"2015","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.numecd.2015.03.015","article-title":"Dietary protein-fiber ratio associates with circulating levels of indoxyl sulfate and p-cresyl sulfate in chronic kidney disease patients","volume":"25","author":"Rossi","year":"2015","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1007\/s12325-010-0059-9","article-title":"Pilot study of probiotic dietary supplementation for promoting healthy kidney function in patients with chronic kidney disease","volume":"27","author":"Ranganathan","year":"2010","journal-title":"Adv. Ther."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"568571","DOI":"10.1155\/2014\/568571","article-title":"Randomized controlled trial of strain-specific probiotic formulation (Renadyl) in dialysis patients","volume":"2014","author":"Natarajan","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"223","DOI":"10.2215\/CJN.05240515","article-title":"Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial","volume":"11","author":"Rossi","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1159\/000381990","article-title":"The Gut as a Source of Inflammation in Chronic Kidney Disease","volume":"130","author":"Lau","year":"2015","journal-title":"Nephron"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1681\/ASN.2014060530","article-title":"Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD","volume":"26","author":"Mishima","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1681\/ASN.2016030278","article-title":"Canagliflozin Slows Progression of Renal Function Decline Independently of Glycemic Effects","volume":"28","author":"Heerspink","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1056\/NEJMoa1611925","article-title":"Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes","volume":"377","author":"Neal","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_166","first-page":"526932","article-title":"P-cresyl sulfate is a valuable predictor of clinical outcomes in pre-ESRD patients","volume":"2014","author":"Lin","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1053\/j.ajkd.2005.12.036","article-title":"A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of AST-120 (Kremezin) in Patients With Moderate to Severe CKD","volume":"47","author":"Schulman","year":"2006","journal-title":"Am. J. Kidney Dis."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"14381","DOI":"10.1038\/srep14381","article-title":"Continuous Reduction of Protein-Bound Uraemic Toxins with Improved Oxidative Stress by Using the Oral Charcoal Adsorbent AST-120 in Haemodialysis Patients","volume":"5","author":"Yamamoto","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1093\/ndt\/gfu061","article-title":"Oral adsorbent AST-120 potentiates the effect of erythropoietin-stimulating agents on Stage 5 chronic kidney disease patients: A randomized crossover study","volume":"29","author":"Wu","year":"2014","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1007\/s00380-015-0785-7","article-title":"Long-term effects of AST-120 on the progression and prognosis of pre-dialysis chronic kidney disease: A 5-year retrospective study","volume":"31","author":"Sato","year":"2016","journal-title":"Heart Vessel."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/4\/252\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:55:49Z","timestamp":1760363749000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/13\/4\/252"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,31]]},"references-count":170,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["toxins13040252"],"URL":"https:\/\/doi.org\/10.3390\/toxins13040252","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,31]]}}}