{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T23:24:25Z","timestamp":1792884265931,"version":"4.5.0"},"reference-count":98,"publisher":"Elsevier BV","issue":"3","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100002661","name":"Fonds De La Recherche Scientifique - FNRS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["kidney-international.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Kidney International"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1016\/j.kint.2025.11.022","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T04:03:30Z","timestamp":1767153810000},"page":"465-473","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"title":["Meta-organismal tryptophan metabolism: an appealing therapeutic target in CKD-MBD"],"prefix":"10.1016","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7087-6798","authenticated-orcid":false,"given":"Guillaume","family":"Fernandes","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Burtey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ward","family":"Zadora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2846-2026","authenticated-orcid":false,"given":"Bjorn","family":"Meijers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"Smout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Labriola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0797-4321","authenticated-orcid":false,"given":"Pieter","family":"Evenepoel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.kint.2025.11.022_bib1","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1038\/ki.2015.230","article-title":"A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010","volume":"88","author":"Mills","year":"2015","journal-title":"Kidney Int"},{"key":"10.1016\/j.kint.2025.11.022_bib2","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1016\/S0140-6736(18)31694-5","article-title":"Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories","volume":"392","author":"Foreman","year":"2018","journal-title":"Lancet Lond Engl"},{"key":"10.1016\/j.kint.2025.11.022_bib3","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1038\/sj.ki.5000414","article-title":"Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO)","volume":"69","author":"Moe","year":"2006","journal-title":"Kidney Int"},{"key":"10.1016\/j.kint.2025.11.022_bib4","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1093\/ndt\/gfs404","article-title":"Control of mineral metabolism and bone disease in haemodialysis patients: which optimal targets?","volume":"28","author":"Fouque","year":"2013","journal-title":"Nephrol Dial Transplant"},{"key":"10.1016\/j.kint.2025.11.022_bib5","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1053\/j.ajkd.2017.09.007","article-title":"Phosphate-binder use in US dialysis patients: prevalence, costs, evidence, and policies","volume":"71","author":"St Peter","year":"2018","journal-title":"Am J Kidney Dis"},{"key":"10.1016\/j.kint.2025.11.022_bib6","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1681\/ASN.2021040554","article-title":"Systematic review and meta-analyses of the effects of phosphate-lowering agents in nondialysis CKD","volume":"33","author":"Lioufas","year":"2022","journal-title":"J Am Soc Nephrol"},{"key":"10.1016\/j.kint.2025.11.022_bib7","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.kint.2024.11.013","article-title":"Chronic kidney disease-mineral and bone disorder: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference","volume":"107","author":"Ketteler","year":"2025","journal-title":"Kidney Int"},{"key":"10.1016\/j.kint.2025.11.022_bib8","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/s41581-019-0111-1","article-title":"Uraemic syndrome of chronic kidney disease: altered remote sensing and signalling","volume":"15","author":"Nigam","year":"2019","journal-title":"Nat Rev Nephrol"},{"key":"10.1016\/j.kint.2025.11.022_bib9","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut microbiota regulation of tryptophan metabolism in health and disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell Host Microbe"},{"key":"10.1016\/j.kint.2025.11.022_bib10","doi-asserted-by":"crossref","first-page":"645","DOI":"10.3390\/toxins14090645","article-title":"Microbial-derived tryptophan catabolites, kidney disease and gut inflammation","volume":"14","author":"Madella","year":"2022","journal-title":"Toxins"},{"key":"10.1016\/j.kint.2025.11.022_bib11","first-page":"185","article-title":"Metaorganisms as the new frontier","volume":"114","author":"Bosch","year":"2011","journal-title":"Zool Jena Ger"},{"key":"10.1016\/j.kint.2025.11.022_bib12","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.3389\/fimmu.2019.02565","article-title":"Tryptophan metabolism in inflammaging: from biomarker to therapeutic target","volume":"10","author":"Sorgdrager","year":"2019","journal-title":"Front Immunol"},{"key":"10.1016\/j.kint.2025.11.022_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.exger.2023.112319","article-title":"Microbiota-derived tryptophan metabolism: impacts on health, aging, and disease","volume":"183","author":"Gupta","year":"2023","journal-title":"Exp Gerontol"},{"key":"10.1016\/j.kint.2025.11.022_bib14","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1093\/ndt\/gfn739","article-title":"Increased indoleamine 2,3-dioxygenase (IDO) activity and elevated serum levels of tryptophan catabolites in patients with chronic kidney disease: a possible link between chronic inflammation and uraemic symptoms","volume":"24","author":"Schefold","year":"2009","journal-title":"Nephrol Dial Transplant"},{"key":"10.1016\/j.kint.2025.11.022_bib15","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":"10.1016\/j.kint.2025.11.022_bib16","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41581-025-01006-4","article-title":"A guide to uraemic toxicity","volume":"22","author":"Glorieux","year":"2026","journal-title":"Nat Rev Nephrol"},{"key":"10.1016\/j.kint.2025.11.022_bib17","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.chembiol.2015.02.005","article-title":"Biosynthetic manipulation of tryptophan in bacteria: pathways and mechanisms","volume":"22","author":"Alkhalaf","year":"2015","journal-title":"Chem Biol"},{"key":"10.1016\/j.kint.2025.11.022_bib18","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0131389","article-title":"Expression of the kynurenine pathway in human peripheral blood mononuclear cells: implications for inflammatory and neurodegenerative disease","volume":"10","author":"Jones","year":"2015","journal-title":"PloS One"},{"key":"10.1016\/j.kint.2025.11.022_bib19","doi-asserted-by":"crossref","first-page":"13033","DOI":"10.1073\/pnas.1517820112","article-title":"Indoleamine 2,3-dioxygenase-1 is protective in atherosclerosis and its metabolites provide new opportunities for drug development","volume":"112","author":"Cole","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.kint.2025.11.022_bib20","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1002\/art.39629","article-title":"Association of increased Treg cell levels with elevated indoleamine 2,3-dioxygenase activity and an imbalanced kynurenine pathway in interferon-positive primary Sj\u00f6gren\u2019s syndrome","volume":"68","author":"Maria","year":"2016","journal-title":"Arthritis Rheumatol"},{"key":"10.1016\/j.kint.2025.11.022_bib21","doi-asserted-by":"crossref","DOI":"10.1177\/1178646919868978","article-title":"The plasma [kynurenine]\/[tryptophan] ratio and indoleamine 2,3-dioxygenase: time for appraisal","volume":"12","author":"Badawy","year":"2019","journal-title":"Int J Tryptophan Res"},{"key":"10.1016\/j.kint.2025.11.022_bib22","doi-asserted-by":"crossref","first-page":"25261","DOI":"10.18632\/oncotarget.15705","article-title":"Peripheral kynurenine\/tryptophan ratio is not a reliable marker of systemic indoleamine 2,3-dioxygenase: a lesson drawn from patients on hemodialysis","volume":"8","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"10.1016\/j.kint.2025.11.022_bib23","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbr.2025.115467","article-title":"Depression in chronic kidney disease: particularities, specific mechanisms and therapeutic considerations, a narrative review","volume":"483","author":"Lefr\u00e8re","year":"2025","journal-title":"Behav Brain Res"},{"key":"10.1016\/j.kint.2025.11.022_bib24","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1016\/j.cell.2020.07.038","article-title":"IL4I1 is a metabolic immune checkpoint that activates the AHR and promotes tumor progression","volume":"182","author":"Sadik","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.kint.2025.11.022_bib25","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/nature24661","article-title":"A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites","volume":"551","author":"Dodd","year":"2017","journal-title":"Nature"},{"key":"10.1016\/j.kint.2025.11.022_bib26","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1007\/s00726-022-03161-5","article-title":"Microbiota-derived tryptophan metabolites in vascular inflammation and cardiovascular disease","volume":"54","author":"Paeslack","year":"2022","journal-title":"Amino Acids"},{"key":"10.1016\/j.kint.2025.11.022_bib27","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.immuni.2013.08.003","article-title":"Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22","volume":"39","author":"Zelante","year":"2013","journal-title":"Immunity"},{"key":"10.1016\/j.kint.2025.11.022_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2021.100575","article-title":"Coordinate regulation of systemic and kidney tryptophan metabolism by the drug transporters OAT1 and OAT3","volume":"296","author":"Granados","year":"2021","journal-title":"J Biol Chem"},{"key":"10.1016\/j.kint.2025.11.022_bib29","doi-asserted-by":"crossref","DOI":"10.1177\/11786469241246674","article-title":"The role of aryl hydrocarbon receptor in bone biology","volume":"17","author":"Vyavahare","year":"2024","journal-title":"Int J Tryptophan Res"},{"key":"10.1016\/j.kint.2025.11.022_bib30","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41581-021-00408-4","article-title":"Uraemic solutes as therapeutic targets in CKD-associated cardiovascular disease","volume":"17","author":"Ravid","year":"2021","journal-title":"Nat Rev Nephrol"},{"key":"10.1016\/j.kint.2025.11.022_bib31","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/s41577-019-0125-8","article-title":"The aryl hydrocarbon receptor: an environmental sensor integrating immune responses in health and disease","volume":"19","author":"Rothhammer","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"10.1016\/j.kint.2025.11.022_bib32","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.chom.2017.06.007","article-title":"Indoleacrylic acid produced by commensal peptostreptococcus species suppresses inflammation","volume":"22","author":"Wlodarska","year":"2017","journal-title":"Cell Host Microbe"},{"key":"10.1016\/j.kint.2025.11.022_bib33","doi-asserted-by":"crossref","DOI":"10.1038\/srep23820","article-title":"Ablating the aryl hydrocarbon receptor (AhR) in CD11c+ cells perturbs intestinal epithelium development and intestinal immunity","volume":"6","author":"Chng","year":"2016","journal-title":"Sci Rep"},{"key":"10.1016\/j.kint.2025.11.022_bib34","doi-asserted-by":"crossref","DOI":"10.3390\/ijms231810825","article-title":"Mixture effects of tryptophan intestinal microbial metabolites on aryl hydrocarbon receptor activity","volume":"23","author":"Vrzalov\u00e1","year":"2022","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.kint.2025.11.022_bib35","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/nrgastro.2013.105","article-title":"Serotonin signalling in the gut\u2014functions, dysfunctions and therapeutic targets","volume":"10","author":"Mawe","year":"2013","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"10.1016\/j.kint.2025.11.022_bib36","doi-asserted-by":"crossref","first-page":"56","DOI":"10.3390\/nu8010056","article-title":"Influence of tryptophan and serotonin on mood and cognition with a possible role of the gut-brain axis","volume":"8","author":"Jenkins","year":"2016","journal-title":"Nutrients"},{"key":"10.1016\/j.kint.2025.11.022_bib37","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/joim.13142","article-title":"Evidence that a deviation in the kynurenine pathway aggravates atherosclerotic disease in humans","volume":"289","author":"Baumgartner","year":"2021","journal-title":"J Intern Med"},{"key":"10.1016\/j.kint.2025.11.022_bib38","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.cmet.2023.06.004","article-title":"Tryptophan metabolism in health and disease","volume":"35","author":"Xue","year":"2023","journal-title":"Cell Metab"},{"key":"10.1016\/j.kint.2025.11.022_bib39","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1093\/cvr\/cvz067","article-title":"The immunometabolic role of indoleamine 2,3-dioxygenase in atherosclerotic cardiovascular disease: immune homeostatic mechanisms in the artery wall","volume":"115","author":"Ketelhuth","year":"2019","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.kint.2025.11.022_bib40","doi-asserted-by":"crossref","DOI":"10.1016\/j.arr.2022.101573","article-title":"Role of indoleamine 2,3-dioxygenase 1 (IDO1) and kynurenine pathway in the regulation of the aging process","volume":"75","author":"Salminen","year":"2022","journal-title":"Ageing Res Rev"},{"key":"10.1016\/j.kint.2025.11.022_bib41","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1016\/j.ekir.2025.02.024","article-title":"Uncovering the link between kynurenic acid pathway and kidney failure","volume":"10","author":"Chamieh","year":"2025","journal-title":"Kidney Int Rep"},{"key":"10.1016\/j.kint.2025.11.022_bib42","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.153019","article-title":"Cell stress response impairs de novo NAD+ biosynthesis in the kidney","volume":"7","author":"Bignon","year":"2022","journal-title":"JCI Insight"},{"key":"10.1016\/j.kint.2025.11.022_bib43","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1016\/j.lfs.2013.05.008","article-title":"Indoxyl sulfate promotes cardiac fibrosis with enhanced oxidative stress in hypertensive rats","volume":"92","author":"Yisireyili","year":"2013","journal-title":"Life Sci"},{"key":"10.1016\/j.kint.2025.11.022_bib44","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1007\/s00018-014-1598-z","article-title":"Redox regulation of endothelial cell fate","volume":"71","author":"Song","year":"2014","journal-title":"Cell Mol Life Sci"},{"key":"10.1016\/j.kint.2025.11.022_bib45","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.kint.2017.11.010","article-title":"Aryl hydrocarbon receptor is activated in patients and mice with chronic kidney disease","volume":"93","author":"Dou","year":"2018","journal-title":"Kidney Int"},{"key":"10.1016\/j.kint.2025.11.022_bib46","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/j.kint.2019.09.029","article-title":"Temporal and tissue-specific activation of aryl hydrocarbon receptor in discrete mouse models of kidney disease","volume":"97","author":"Walker","year":"2020","journal-title":"Kidney Int"},{"key":"10.1016\/j.kint.2025.11.022_bib47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000365217","article-title":"Indoxyl sulfate induces IL-6 expression in vascular endothelial and smooth muscle cells through OAT3-mediated uptake and activation of AhR\/NF-\u03baB pathway","volume":"128","author":"Adelibieke","year":"2014","journal-title":"Nephron Exp Nephrol"},{"key":"10.1016\/j.kint.2025.11.022_bib48","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1093\/ndt\/gfy325","article-title":"Endothelial cells exposed to phosphate and indoxyl sulphate promote vascular calcification through interleukin-8 secretion","volume":"34","author":"Bouabdallah","year":"2019","journal-title":"Nephrol Dial Transplant"},{"key":"10.1016\/j.kint.2025.11.022_bib49","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":"10.1016\/j.kint.2025.11.022_bib50","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1681\/ASN.2018060609","article-title":"Indoxyl sulfate and p-cresyl sulfate promote vascular calcification and associate with glucose intolerance","volume":"30","author":"Opdebeeck","year":"2019","journal-title":"J Am Soc Nephrol"},{"key":"10.1016\/j.kint.2025.11.022_bib51","doi-asserted-by":"crossref","first-page":"C126","DOI":"10.1152\/ajpcell.00329.2011","article-title":"Indoxyl sulfate promotes vascular smooth muscle cell senescence with upregulation of p53, p21, and prelamin A through oxidative stress","volume":"303","author":"Muteliefu","year":"2012","journal-title":"Am J Physiol Cell Physiol"},{"key":"10.1016\/j.kint.2025.11.022_bib52","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1093\/ndt\/gfv250","article-title":"Indoxyl sulfate suppresses hepatic fetuin-A expression via the aryl hydrocarbon receptor in HepG2 cells","volume":"30","author":"Ochi","year":"2015","journal-title":"Nephrol Dial Transplant"},{"key":"10.1016\/j.kint.2025.11.022_bib53","doi-asserted-by":"crossref","DOI":"10.1172\/JCI142260","article-title":"Tryptophan metabolites suppress the Wnt pathway and promote adverse limb events in chronic kidney disease","volume":"132","author":"Arinze","year":"2022","journal-title":"J Clin Invest"},{"key":"10.1016\/j.kint.2025.11.022_bib54","doi-asserted-by":"crossref","first-page":"100","DOI":"10.3390\/toxins14020100","article-title":"Aryl hydrocarbon receptor inhibition restores indoxyl sulfate-mediated endothelial dysfunction in rat aortic rings","volume":"14","author":"Nguyen","year":"2022","journal-title":"Toxins"},{"key":"10.1016\/j.kint.2025.11.022_bib55","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/ki.2013.133","article-title":"Indolic uremic solutes increase tissue factor production in endothelial cells by the aryl hydrocarbon receptor pathway","volume":"84","author":"Gondouin","year":"2013","journal-title":"Kidney Int"},{"key":"10.1016\/j.kint.2025.11.022_bib56","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1182\/blood-2016-10-744060","article-title":"Indoxyl sulfate induces platelet hyperactivity and contributes to chronic kidney disease-associated thrombosis in mice","volume":"129","author":"Yang","year":"2017","journal-title":"Blood"},{"key":"10.1016\/j.kint.2025.11.022_bib57","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1681\/ASN.2017080929","article-title":"Uremic solute-aryl hydrocarbon receptor-tissue factor axis associates with thrombosis after vascular injury in humans","volume":"29","author":"Kolachalama","year":"2018","journal-title":"J Am Soc Nephrol"},{"key":"10.1016\/j.kint.2025.11.022_bib58","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":"10.1016\/j.kint.2025.11.022_bib59","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.atherosclerosis.2008.08.014","article-title":"The kynurenines are associated with oxidative stress, inflammation and the prevalence of cardiovascular disease in patients with end-stage renal disease","volume":"204","author":"Pawlak","year":"2009","journal-title":"Atherosclerosis"},{"key":"10.1016\/j.kint.2025.11.022_bib60","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1093\/eurheartj\/eht264","article-title":"Urinary excretion of kynurenine and tryptophan, cardiovascular events, and mortality after elective coronary angiography","volume":"34","author":"Pedersen","year":"2013","journal-title":"Eur Heart J"},{"key":"10.1016\/j.kint.2025.11.022_bib61","doi-asserted-by":"crossref","first-page":"8770","DOI":"10.3390\/ijms25168770","article-title":"Indoxyl sulfate inhibits osteogenesis in bone marrow mesenchymal stem cells through the AhR\/Hes1 pathway","volume":"25","author":"Hsieh","year":"2024","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.kint.2025.11.022_bib62","doi-asserted-by":"crossref","first-page":"7483","DOI":"10.3390\/ijms21207483","article-title":"Resveratrol rescue indoxyl sulfate-induced deterioration of osteoblastogenesis via the aryl hydrocarbon receptor \/MAPK pathway","volume":"21","author":"Liu","year":"2020","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.kint.2025.11.022_bib63","doi-asserted-by":"crossref","DOI":"10.1016\/j.exger.2019.110818","article-title":"Kynurenine suppresses osteoblastic cell energetics in vitro and osteoblast numbers in vivo","volume":"130","author":"Pierce","year":"2020","journal-title":"Exp Gerontol"},{"key":"10.1016\/j.kint.2025.11.022_bib64","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":"Nii-Kono","year":"2007","journal-title":"Kidney Int"},{"key":"10.1016\/j.kint.2025.11.022_bib65","doi-asserted-by":"crossref","first-page":"3486","DOI":"10.3390\/ijms21103486","article-title":"Concentration and duration of indoxyl sulfate exposure affects osteoclastogenesis by regulating NFATc1 via aryl hydrocarbon receptor","volume":"21","author":"Liu","year":"2020","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.kint.2025.11.022_bib66","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.bbrc.2014.05.114","article-title":"Aryl hydrocarbon receptor catabolic activity in bone metabolism is osteoclast dependent in vivo","volume":"450","author":"Yu T yong","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.kint.2025.11.022_bib67","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.pbiomolbio.2017.12.005","article-title":"The role of aryl hydrocarbon receptor in bone remodeling","volume":"134","author":"Yu","year":"2018","journal-title":"Prog Biophys Mol Biol"},{"key":"10.1016\/j.kint.2025.11.022_bib68","doi-asserted-by":"crossref","first-page":"11115","DOI":"10.1073\/pnas.1220919110","article-title":"Smoke carcinogens cause bone loss through the aryl hydrocarbon receptor and induction of Cyp1 enzymes","volume":"110","author":"Iqbal","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.kint.2025.11.022_bib69","doi-asserted-by":"crossref","first-page":"836","DOI":"10.3389\/fphys.2017.00836","article-title":"Elevated levels of peripheral kynurenine decrease bone strength in rats with chronic kidney disease","volume":"8","author":"Kalaska","year":"2017","journal-title":"Front Physiol"},{"key":"10.1016\/j.kint.2025.11.022_bib70","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1038\/nrrheum.2009.217","article-title":"Osteoimmunology and the effects of the immune system on bone","volume":"5","author":"Takayanagi","year":"2009","journal-title":"Nat Rev Rheumatol"},{"key":"10.1016\/j.kint.2025.11.022_bib71","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1038\/ni.2077","article-title":"Indoleamine 2,3-dioxygenase is a signaling protein in long-term tolerance by dendritic cells","volume":"12","author":"Pallotta","year":"2011","journal-title":"Nat Immunol"},{"key":"10.1016\/j.kint.2025.11.022_bib72","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/cr.2008.63","article-title":"The aryl hydrocarbon receptor: a regulator of Th17 and Treg cell development in disease","volume":"18","author":"Ho","year":"2008","journal-title":"Cell Res"},{"key":"10.1016\/j.kint.2025.11.022_bib73","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2022.962969","article-title":"Pathomechanisms of bone loss in rheumatoid arthritis","volume":"9","author":"Sakthiswary","year":"2022","journal-title":"Front Med"},{"key":"10.1016\/j.kint.2025.11.022_bib74","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1136\/gutjnl-2014-306947","article-title":"Bone marrow Th17 TNF\u03b1 cells induce osteoclast differentiation, and link bone destruction to IBD","volume":"64","author":"Ciucci","year":"2015","journal-title":"Gut"},{"key":"10.1016\/j.kint.2025.11.022_bib75","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcmd.2022.102702","article-title":"Characterization of peripheral T helper 17 (Th17) cells phenotype in postmenopausal women with estrogen insufficiency","volume":"98","author":"Bhadricha","year":"2023","journal-title":"Blood Cells Mol Dis"},{"key":"10.1016\/j.kint.2025.11.022_bib76","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1093\/ndt\/gfx222","article-title":"Inflammation induces osteoclast differentiation from peripheral mononuclear cells in chronic kidney disease patients: crosstalk between the immune and bone systems","volume":"33","author":"Cafiero","year":"2018","journal-title":"Nephrol Dial Transplant"},{"key":"10.1016\/j.kint.2025.11.022_bib77","doi-asserted-by":"crossref","first-page":"2334","DOI":"10.1210\/jc.2018-02481","article-title":"The detrimental effects of kynurenine, a tryptophan metabolite, on human bone metabolism","volume":"104","author":"Kim","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"10.1016\/j.kint.2025.11.022_bib78","doi-asserted-by":"crossref","DOI":"10.3390\/ijms222011265","article-title":"Toxic effects of indoxyl sulfate on osteoclastogenesis and osteoblastogenesis","volume":"22","author":"Shyu","year":"2021","journal-title":"Int J Mol Sci"},{"key":"10.1016\/j.kint.2025.11.022_bib79","article-title":"The uremic toxin indoxyl sulfate decreases osteocyte RANKL\/OPG and increases Wnt inhibitor RNA expression that is reversed by PTH","volume":"9","author":"Chen","year":"2025","journal-title":"JBMR Plus"},{"key":"10.1016\/j.kint.2025.11.022_bib80","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1038\/s41598-024-53164-3","article-title":"Dose-dependent exposure to indoxyl sulfate alters AHR signaling, sirtuins gene expression, oxidative DNA damage, and bone mineral status in rats","volume":"14","author":"Karbowska","year":"2024","journal-title":"Sci Rep"},{"key":"10.1016\/j.kint.2025.11.022_bib81","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1002\/jbmr.4125","article-title":"Picolinic acid, a catabolite of tryptophan, has an anabolic effect on bone in vivo","volume":"35","author":"Duque","year":"2020","journal-title":"J Bone Miner Res"},{"key":"10.1016\/j.kint.2025.11.022_bib82","doi-asserted-by":"crossref","DOI":"10.1016\/j.bone.2023.116811","article-title":"Orchiectomy sensitizes cortical bone in male mice to the harmful effects of kynurenine","volume":"173","author":"Bensreti","year":"2023","journal-title":"Bone"},{"key":"10.1016\/j.kint.2025.11.022_bib83","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.bone.2018.05.022","article-title":"LP533401 restores bone health in 5\/6 nephrectomized rats by a decrease of gut-derived serotonin and regulation of serum phosphate through the inhibition of phosphate co-transporters expression in the kidneys","volume":"113","author":"Pawlak","year":"2018","journal-title":"Bone"},{"key":"10.1016\/j.kint.2025.11.022_bib84","doi-asserted-by":"crossref","DOI":"10.1016\/j.exger.2019.110778","article-title":"The multiple faces of tryptophan in bone biology","volume":"129","author":"Al Saedi","year":"2020","journal-title":"Exp Gerontol"},{"key":"10.1016\/j.kint.2025.11.022_bib85","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/s41581-023-00736-7","article-title":"Inflammation and gut dysbiosis as drivers of CKD-MBD","volume":"19","author":"Evenepoel","year":"2023","journal-title":"Nat Rev Nephrol"},{"key":"10.1016\/j.kint.2025.11.022_bib86","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/s41591-018-0060-4","article-title":"Genetic deficiency of indoleamine 2,3-dioxygenase promotes gut microbiota-mediated metabolic health","volume":"24","author":"Laurans","year":"2018","journal-title":"Nat Med"},{"key":"10.1016\/j.kint.2025.11.022_bib87","doi-asserted-by":"crossref","first-page":"4457","DOI":"10.1038\/s41467-020-18262-6","article-title":"Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity","volume":"11","author":"Yang","year":"2020","journal-title":"Nat Commun"},{"key":"10.1016\/j.kint.2025.11.022_bib88","doi-asserted-by":"crossref","first-page":"1964","DOI":"10.1038\/s41564-024-01737-3","article-title":"Dietary fibre directs microbial tryptophan metabolism via metabolic interactions in the gut microbiota","volume":"9","author":"Sinha","year":"2024","journal-title":"Nat Microbiol"},{"key":"10.1016\/j.kint.2025.11.022_bib89","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":"10.1016\/j.kint.2025.11.022_bib90","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/s41387-018-0046-9","article-title":"Associations of serum indolepropionic acid, a gut microbiota metabolite, with type 2 diabetes and low-grade inflammation in high-risk individuals","volume":"8","author":"Tuomainen","year":"2018","journal-title":"Nutr Diabetes"},{"key":"10.1016\/j.kint.2025.11.022_bib91","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/s41573-025-01172-x","article-title":"The aryl hydrocarbon receptor: a rehabilitated target for therapeutic immune modulation","volume":"24","author":"Polonio","year":"2025","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.kint.2025.11.022_bib92","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/S0026-895X(24)12541-2","article-title":"Resveratrol has antagonist activity on the aryl hydrocarbon receptor: implications for prevention of dioxin toxicity","volume":"56","author":"Casper","year":"1999","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.kint.2025.11.022_bib93","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.biochi.2023.05.001","article-title":"Effects of resveratrol on inflammation and oxidative stress induced by the uremic toxin indoxyl sulfate in murine macrophage-like RAW 264.7","volume":"213","author":"Alvarenga","year":"2023","journal-title":"Biochimie"},{"key":"10.1016\/j.kint.2025.11.022_bib94","doi-asserted-by":"crossref","first-page":"161","DOI":"10.2215\/CJN.0000000000000337","article-title":"Effect of resveratrol on endothelial function in patients with CKD and diabetes: a randomized controlled trial","volume":"19","author":"Gimblet","year":"2024","journal-title":"Clin J Am Soc Nephrol"},{"key":"10.1016\/j.kint.2025.11.022_bib95","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1053\/j.jrn.2022.01.010","article-title":"Can Resveratrol supplementation reduce uremic toxin plasma levels from the gut microbiota in nondialyzed patients with chronic kidney disease?","volume":"32","author":"Alvarenga","year":"2022","journal-title":"J Ren Nutr"},{"key":"10.1016\/j.kint.2025.11.022_bib96","doi-asserted-by":"crossref","first-page":"192","DOI":"10.3390\/biomedicines9020192","article-title":"Immunomodulatory role of urolithin A on metabolic diseases","volume":"9","author":"Toney","year":"2021","journal-title":"Biomedicines"},{"key":"10.1016\/j.kint.2025.11.022_bib97","doi-asserted-by":"crossref","first-page":"86","DOI":"10.3390\/metabo8040086","article-title":"Urolithin A is a dietary microbiota-derived human aryl hydrocarbon receptor antagonist","volume":"8","author":"Muku","year":"2018","journal-title":"Metabolites"},{"key":"10.1016\/j.kint.2025.11.022_bib98","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/s41581-020-00345-8","article-title":"Food as medicine: targeting the uraemic phenotype in chronic kidney disease","volume":"17","author":"Mafra","year":"2021","journal-title":"Nat Rev Nephrol"}],"container-title":["Kidney International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0085253825010191?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0085253825010191?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T16:57:04Z","timestamp":1786035424000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0085253825010191"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":98,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["S0085253825010191"],"URL":"https:\/\/doi.org\/10.1016\/j.kint.2025.11.022","relation":{},"ISSN":["0085-2538"],"issn-type":[{"value":"0085-2538","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Meta-organismal tryptophan metabolism: an appealing therapeutic target in CKD-MBD","name":"articletitle","label":"Article Title"},{"value":"Kidney International","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.kint.2025.11.022","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.","name":"copyright","label":"Copyright"}]}}