{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T10:20:48Z","timestamp":1794565248599,"version":"4.9.1"},"reference-count":220,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Nephrol"],"published-print":{"date-parts":[[2021,6]]},"DOI":"10.1038\/s41581-021-00408-4","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T09:03:10Z","timestamp":1616490190000},"page":"402-416","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["Uraemic solutes as therapeutic targets in CKD-associated cardiovascular disease"],"prefix":"10.1038","volume":"17","author":[{"given":"Jonathan D.","family":"Ravid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Hassan","family":"Kamel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6663-6058","authenticated-orcid":false,"given":"Vipul C.","family":"Chitalia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,23]]},"reference":[{"key":"408_CR1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0158765","volume":"11","author":"NR Hill","year":"2016","unstructured":"Hill, N. R. et al. Global prevalence of chronic kidney disease \u2014 a systematic review and meta-analysis. PLoS ONE 11, e0158765 (2016).","journal-title":"PLoS ONE"},{"key":"408_CR2","unstructured":"Centers for Disease Control and Prevention. Chronic Kidney Disease Surveillance System \u2014 United States. CDC https:\/\/nccd.cdc.gov\/ckd\/default.aspx (2021)."},{"key":"408_CR3","first-page":"1","volume":"64","author":"J Xu","year":"2016","unstructured":"Xu, J., Murphy, S. L., Kochanek, K. D. & Bastian, B. A. Deaths: final data for 2013. Natl Vital Stat. Rep. 64, 1\u2013119 (2016).","journal-title":"Natl Vital Stat. Rep."},{"key":"408_CR4","doi-asserted-by":"publisher","first-page":"414","DOI":"10.2471\/BLT.17.206441","volume":"96","author":"VA Luyckx","year":"2018","unstructured":"Luyckx, V. A., Tonelli, M. & Stanifer, J. W. The global burden of kidney disease and the sustainable development goals. Bull. World Health Organ. 96, 414\u2013422D (2018).","journal-title":"Bull. World Health Organ."},{"key":"408_CR5","unstructured":"Centers for Disease Control and Prevention. Chronic kidney disease in the United States, 2019 (CDC, 2019)."},{"key":"408_CR6","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1681\/ASN.2012010037","volume":"23","author":"IR Whitman","year":"2012","unstructured":"Whitman, I. R., Feldman, H. I. & Deo, R. CKD and sudden cardiac death: epidemiology, mechanisms, and therapeutic approaches. J. Am. Soc. Nephrol. 23, 1929\u20131939 (2012).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR7","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1016\/j.semnephrol.2018.08.008","volume":"38","author":"DM Charytan","year":"2018","unstructured":"Charytan, D. M. Introduction: cardiovascular disease in chronic kidney disease. Semin. Nephrol. 38, 541 (2018).","journal-title":"Semin. Nephrol."},{"key":"408_CR8","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.semnephrol.2018.08.002","volume":"38","author":"DJ Weaver","year":"2018","unstructured":"Weaver, D. J. & Mitsnefes, M. Cardiovascular disease in children and adolescents with chronic kidney disease. Semin. Nephrol. 38, 559\u2013569 (2018).","journal-title":"Semin. Nephrol."},{"key":"408_CR9","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-016412","volume":"7","author":"MN Temgoua","year":"2017","unstructured":"Temgoua, M. N., Danwang, C., Agbor, V. N. & Noubiap, J. J. Prevalence, incidence and associated mortality of cardiovascular disease in patients with chronic kidney disease in low- and middle-income countries: a protocol for a systematic review and meta-analysis. BMJ Open 7, e016412 (2017).","journal-title":"BMJ Open"},{"key":"408_CR10","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/j.kint.2016.09.049","volume":"91","author":"RO Mathew","year":"2017","unstructured":"Mathew, R. O. et al. Diagnosis and management of atherosclerotic cardiovascular disease in chronic kidney disease: a review. Kidney Int. 91, 797\u2013807 (2017).","journal-title":"Kidney Int."},{"key":"408_CR11","doi-asserted-by":"publisher","first-page":"2073","DOI":"10.1016\/S0140-6736(10)60674-5","volume":"375","author":"Chronic Kidney Disease Prognosis Consortium","year":"2010","unstructured":"Chronic Kidney Disease Prognosis Consortium. et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 375, 2073\u20132081 (2010).","journal-title":"Lancet"},{"key":"408_CR12","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1038\/ki.2010.536","volume":"79","author":"M van der Velde","year":"2011","unstructured":"van der Velde, M. et al. Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts. Kidney Int. 79, 1341\u20131352 (2011).","journal-title":"Kidney Int."},{"key":"408_CR13","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/S0140-6736(13)60595-4","volume":"382","author":"RT Gansevoort","year":"2013","unstructured":"Gansevoort, R. T. et al. Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention. Lancet 382, 339\u2013352 (2013).","journal-title":"Lancet"},{"key":"408_CR14","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1001\/jamacardio.2016.4652","volume":"2","author":"N Bansal","year":"2017","unstructured":"Bansal, N. et al. Absolute rates of heart failure, coronary heart disease, and stroke in chronic kidney disease: an analysis of 3 community-based cohort studies. JAMA Cardiol. 2, 314\u2013318 (2017).","journal-title":"JAMA Cardiol."},{"key":"408_CR15","doi-asserted-by":"publisher","first-page":"1662","DOI":"10.1016\/S0140-6736(12)61350-6","volume":"380","author":"CS Fox","year":"2012","unstructured":"Fox, C. S. et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet 380, 1662\u20131673 (2012).","journal-title":"Lancet"},{"key":"408_CR16","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1016\/S0140-6736(12)60572-8","volume":"380","author":"M Tonelli","year":"2012","unstructured":"Tonelli, M. et al. Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study. Lancet 380, 807\u2013814 (2012).","journal-title":"Lancet"},{"key":"408_CR17","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1016\/j.amjcard.2012.07.021","volume":"110","author":"M Natsuaki","year":"2012","unstructured":"Natsuaki, M. et al. Renal function and effect of statin therapy on cardiovascular outcomes in patients undergoing coronary revascularization (from the CREDO-Kyoto PCI\/CABG Registry Cohort-2). Am. J. Cardiol. 110, 1568\u20131577 (2012).","journal-title":"Am. J. Cardiol."},{"key":"408_CR18","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1056\/NEJMoa043545","volume":"353","author":"C Wanner","year":"2005","unstructured":"Wanner, C. et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N. Engl. J. Med. 353, 238\u2013248 (2005).","journal-title":"N. Engl. J. Med."},{"key":"408_CR19","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1016\/j.jacc.2009.10.043","volume":"55","author":"DJ Angiolillo","year":"2010","unstructured":"Angiolillo, D. J. et al. Impact of chronic kidney disease on platelet function profiles in diabetes mellitus patients with coronary artery disease taking dual antiplatelet therapy. J. Am. Coll. Cardiol. 55, 1139\u20131146 (2010).","journal-title":"J. Am. Coll. Cardiol."},{"key":"408_CR20","doi-asserted-by":"publisher","first-page":"2160","DOI":"10.1097\/TP.0000000000001002","volume":"100","author":"VR Sorensen","year":"2016","unstructured":"Sorensen, V. R., Heaf, J., Wehberg, S. & Sorensen, S. S. Survival benefit in renal transplantation despite high comorbidity. Transplantation 100, 2160\u20132167 (2016).","journal-title":"Transplantation"},{"key":"408_CR21","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1001\/jamasurg.2014.2038","volume":"150","author":"A Rana","year":"2015","unstructured":"Rana, A. et al. Survival benefit of solid-organ transplant in the United States. JAMA Surg. 150, 252\u2013259 (2015).","journal-title":"JAMA Surg."},{"key":"408_CR22","doi-asserted-by":"publisher","first-page":"2035","DOI":"10.2215\/CJN.05500809","volume":"4","author":"TE Pesavento","year":"2009","unstructured":"Pesavento, T. E. Kidney transplantation in the context of renal replacement therapy. Clin. J. Am. Soc. Nephrol. 4, 2035\u20132039 (2009).","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"408_CR23","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1097\/01.tp.0000259621.56861.31","volume":"83","author":"PS Rao","year":"2007","unstructured":"Rao, P. S. et al. Renal transplantation in elderly patients older than 70 years of age: results from the scientific registry of transplant recipients. Transplantation 83, 1069\u20131074 (2007).","journal-title":"Transplantation"},{"key":"408_CR24","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1093\/bmb\/ldt012","volume":"106","author":"MJ Bottomley","year":"2013","unstructured":"Bottomley, M. J. & Harden, P. N. Update on the long-term complications of renal transplantation. Br. Med. Bull. 106, 117\u2013134 (2013).","journal-title":"Br. Med. Bull."},{"key":"408_CR25","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1111\/j.1525-139X.2008.00454.x","volume":"21","author":"ML Gross","year":"2008","unstructured":"Gross, M. L. & Ritz, E. Hypertrophy and fibrosis in the cardiomyopathy of uremia\u2013beyond coronary heart disease. Semin. Dial. 21, 308\u2013318 (2008).","journal-title":"Semin. Dial."},{"key":"408_CR26","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.2215\/CJN.15651219","volume":"15","author":"AM Price","year":"2020","unstructured":"Price, A. M. et al. Changes in blood pressure and arterial hemodynamics following living kidney donation. Clin. J. Am. Soc. Nephrol. 15, 1330\u20131339 (2020).","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"408_CR27","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1681\/ASN.2013040348","volume":"25","author":"SM Ting","year":"2014","unstructured":"Ting, S. M. et al. Functional cardiovascular reserve predicts survival pre-kidney and post-kidney transplantation. J. Am. Soc. Nephrol. 25, 187\u2013195 (2014).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR28","doi-asserted-by":"publisher","first-page":"1721","DOI":"10.1093\/ndt\/gfw009","volume":"31","author":"R Poesen","year":"2016","unstructured":"Poesen, R. et al. The influence of renal transplantation on retained microbial-human co-metabolites. Nephrol. Dial. Transpl. 31, 1721\u20131729 (2016).","journal-title":"Nephrol. Dial. Transpl."},{"key":"408_CR29","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1253\/circj.CJ-15-0949","volume":"80","author":"S Liabeuf","year":"2016","unstructured":"Liabeuf, S. et al. Levels of indoxyl sulfate in kidney transplant patients, and the relationship with hard outcomes. Circ. J. 80, 722\u2013730 (2016).","journal-title":"Circ. J."},{"key":"408_CR30","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3390\/toxins10060229","volume":"10","author":"S Liabeuf","year":"2018","unstructured":"Liabeuf, S., Cheddani, L. & Massy, Z. A. Uremic toxins and clinical outcomes: the impact of kidney transplantation. Toxins 10, 229 (2018).","journal-title":"Toxins"},{"key":"408_CR31","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1038\/s41581-020-0299-0","volume":"16","author":"R Masereeuw","year":"2020","unstructured":"Masereeuw, R. & Verhaar, M. C. Innovations in approaches to remove uraemic toxins. Nat. Rev. Nephrol. 16, 552\u2013553 (2020).","journal-title":"Nat. Rev. Nephrol."},{"key":"408_CR32","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1038\/s41581-020-0293-6","volume":"16","author":"I Geremia","year":"2020","unstructured":"Geremia, I. & Stamatialis, D. Innovations in dialysis membranes for improved kidney replacement therapy. Nat. Rev. Nephrol. 16, 550\u2013551 (2020).","journal-title":"Nat. Rev. Nephrol."},{"key":"408_CR33","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1177\/039139880102401004","volume":"24","author":"R Vanholder","year":"2001","unstructured":"Vanholder, R. et al. Uremic toxicity: present state of the art. Int. J. Artif. Organs 24, 695\u2013725 (2001).","journal-title":"Int. J. Artif. Organs"},{"key":"408_CR34","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1681\/ASN.2011121175","volume":"23","author":"F Duranton","year":"2012","unstructured":"Duranton, F. et al. Normal and pathologic concentrations of uremic toxins. J. Am. Soc. Nephrol. 23, 1258\u20131270 (2012).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR35","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1046\/j.1492-7535.2003.00034.x","volume":"7","author":"RC Vanholder","year":"2003","unstructured":"Vanholder, R. C. & Glorieux, G. L. An overview of uremic toxicity. Hemodial. Int. 7, 156\u2013161 (2003).","journal-title":"Hemodial. Int."},{"key":"408_CR36","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1056\/NEJMoa1109400","volume":"368","author":"WH Tang","year":"2013","unstructured":"Tang, W. H. et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 368, 1575\u20131584 (2013).","journal-title":"N. Engl. J. Med."},{"key":"408_CR37","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1681\/ASN.2007070760","volume":"19","author":"S Mathew","year":"2008","unstructured":"Mathew, S. et al. The mechanism of phosphorus as a cardiovascular risk factor in CKD. J. Am. Soc. Nephrol. 19, 1092\u20131105 (2008).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR38","doi-asserted-by":"publisher","first-page":"647","DOI":"10.3390\/toxins11110647","volume":"11","author":"I Vogt","year":"2019","unstructured":"Vogt, I., Haffner, D. & Leifheit-Nestler, M. FGF23 and phosphate-cardiovascular toxins in CKD. Toxins 11, 647 (2019).","journal-title":"Toxins"},{"key":"408_CR39","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1007\/s00467-016-3527-x","volume":"32","author":"P Evenepoel","year":"2017","unstructured":"Evenepoel, P., Poesen, R. & Meijers, B. The gut-kidney axis. Pediatr. Nephrol. 32, 2005\u20132014 (2017).","journal-title":"Pediatr. Nephrol."},{"key":"408_CR40","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05470-4","volume":"9","author":"HM Roager","year":"2018","unstructured":"Roager, H. M. & Licht, T. R. Microbial tryptophan catabolites in health and disease. Nat. Commun. 9, 3294 (2018).","journal-title":"Nat. Commun."},{"key":"408_CR41","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1007\/s00726-010-0787-9","volume":"41","author":"LR Kolodziej","year":"2011","unstructured":"Kolodziej, L. R., Paleolog, E. M. & Williams, R. O. Kynurenine metabolism in health and disease. Amino Acids 41, 1173\u20131183 (2011).","journal-title":"Amino Acids"},{"key":"408_CR42","doi-asserted-by":"publisher","first-page":"15496","DOI":"10.1016\/S0021-9258(18)82284-0","volume":"268","author":"K Saito","year":"1993","unstructured":"Saito, K., Crowley, J. S., Markey, S. P. & Heyes, M. P. A mechanism for increased quinolinic acid formation following acute systemic immune stimulation. J. Biol. Chem. 268, 15496\u201315503 (1993).","journal-title":"J. Biol. Chem."},{"key":"408_CR43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4137\/IJTR.S2097","volume":"2","author":"Y Chen","year":"2009","unstructured":"Chen, Y. & Guillemin, G. J. Kynurenine pathway metabolites in humans: disease and healthy states. Int. J. Tryptophan Res. 2, 1\u201319 (2009).","journal-title":"Int. J. Tryptophan Res."},{"key":"408_CR44","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1007\/s11095-005-2486-x","volume":"22","author":"T Deguchi","year":"2005","unstructured":"Deguchi, T., Kouno, Y., Terasaki, T., Takadate, A. & Otagiri, M. Differential contributions of rOat1 (Slc22a6) and rOat3 (Slc22a8) to the in vivo renal uptake of uremic toxins in rats. Pharm. Res. 22, 619\u2013627 (2005).","journal-title":"Pharm. Res."},{"key":"408_CR45","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.phrs.2011.11.003","volume":"65","author":"Y Uwai","year":"2012","unstructured":"Uwai, Y., Honjo, H. & Iwamoto, K. Interaction and transport of kynurenic acid via human organic anion transporters hOAT1 and hOAT3. Pharmacol. Res. 65, 254\u2013260 (2012).","journal-title":"Pharmacol. Res."},{"key":"408_CR46","doi-asserted-by":"publisher","first-page":"F565","DOI":"10.1152\/ajprenal.2000.279.3.F565","volume":"279","author":"K Saito","year":"2000","unstructured":"Saito, K. et al. Mechanism of increases in L-kynurenine and quinolinic acid in renal insufficiency. Am. J. Physiol. Renal Physiol. 279, F565\u2013F572 (2000).","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"408_CR47","doi-asserted-by":"publisher","first-page":"2494","DOI":"10.1056\/NEJMcibr1604458","volume":"374","author":"H Tilg","year":"2016","unstructured":"Tilg, H. A gut feeling about thrombosis. N. Engl. J. Med. 374, 2494\u20132496 (2016).","journal-title":"N. Engl. J. Med."},{"key":"408_CR48","doi-asserted-by":"publisher","first-page":"635","DOI":"10.3390\/toxins11110635","volume":"11","author":"CC Pelletier","year":"2019","unstructured":"Pelletier, C. C. et al. Elevation of trimethylamine-N-oxide in chronic kidney disease: contribution of decreased glomerular filtration rate. Toxins 11, 635 (2019).","journal-title":"Toxins"},{"key":"408_CR49","doi-asserted-by":"publisher","first-page":"2208","DOI":"10.1097\/01.ASN.0000133041.27682.A2","volume":"15","author":"GA Block","year":"2004","unstructured":"Block, G. A. et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J. Am. Soc. Nephrol. 15, 2208\u20132218 (2004).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR50","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1681\/ASN.2005020132","volume":"17","author":"AK Cheung","year":"2006","unstructured":"Cheung, A. K. et al. Serum beta-2 microglobulin levels predict mortality in dialysis patients: results of the HEMO study. J. Am. Soc. Nephrol. 17, 546\u2013555 (2006).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR51","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1093\/ndt\/gfp592","volume":"25","author":"S Liabeuf","year":"2010","unstructured":"Liabeuf, S. et al. Free p-cresylsulphate is a predictor of mortality in patients at different stages of chronic kidney disease. Nephrol. Dial. Transpl. 25, 1183\u20131191 (2010).","journal-title":"Nephrol. Dial. Transpl."},{"key":"408_CR52","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1093\/ndt\/gfr453","volume":"27","author":"IW Wu","year":"2012","unstructured":"Wu, I. W. et al. Serum free p-cresyl sulfate levels predict cardiovascular and all-cause mortality in elderly hemodialysis patients \u2014 a prospective cohort study. Nephrol. Dial. Transpl. 27, 1169\u20131175 (2012).","journal-title":"Nephrol. Dial. Transpl."},{"key":"408_CR53","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1681\/ASN.2014111063","volume":"27","author":"JR Stubbs","year":"2016","unstructured":"Stubbs, J. R. et al. Serum trimethylamine-N-oxide is elevated in ckd and correlates with coronary atherosclerosis burden. J. Am. Soc. Nephrol. 27, 305\u2013313 (2016).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR54","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3390\/toxins9010025","volume":"9","author":"CC Wu","year":"2017","unstructured":"Wu, C. C., Hung, S. C., Kuo, K. L. & Tarng, D. C. Impact of indoxyl sulfate on progenitor cell-related neovascularization of peripheral arterial disease and post-angioplasty thrombosis of dialysis vascular access. Toxins 9, 25 (2017).","journal-title":"Toxins"},{"key":"408_CR55","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/j.kint.2017.03.053","volume":"92","author":"JAP Tomlinson","year":"2017","unstructured":"Tomlinson, J. A. P. & Wheeler, D. C. The role of trimethylamine N-oxide as a mediator of cardiovascular complications in chronic kidney disease. Kidney Int. 92, 809\u2013815 (2017).","journal-title":"Kidney Int."},{"key":"408_CR56","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002816","volume":"5","author":"V Senthong","year":"2016","unstructured":"Senthong, V. et al. Intestinal microbiota-generated metabolite trimethylamine-N-oxide and 5-year mortality risk in stable coronary artery disease: the contributory role of intestinal microbiota in a COURAGE-like patient cohort. J. Am. Heart Assoc. 5, e002816 (2016).","journal-title":"J. Am. Heart Assoc."},{"key":"408_CR57","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.arcmed.2012.08.002","volume":"43","author":"CJ Lin","year":"2012","unstructured":"Lin, C. J. et al. Indoxyl sulfate predicts cardiovascular disease and renal function deterioration in advanced chronic kidney disease. Arch. Med. Res. 43, 451\u2013456 (2012).","journal-title":"Arch. Med. Res."},{"key":"408_CR58","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1016\/j.jfma.2019.03.005","volume":"118","author":"PC Fan","year":"2019","unstructured":"Fan, P. C. et al. Serum indoxyl sulfate predicts adverse cardiovascular events in patients with chronic kidney disease. J. Formos. Med. Assoc. 118, 1099\u20131106 (2019).","journal-title":"J. Formos. Med. Assoc."},{"key":"408_CR59","doi-asserted-by":"publisher","first-page":"1174","DOI":"10.1038\/ki.2008.31","volume":"73","author":"BK Meijers","year":"2008","unstructured":"Meijers, B. K. et al. Free p-cresol is associated with cardiovascular disease in hemodialysis patients. Kidney Int. 73, 1174\u20131180 (2008).","journal-title":"Kidney Int."},{"key":"408_CR60","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1161\/ATVBAHA.114.304674","volume":"35","author":"ER Pedersen","year":"2015","unstructured":"Pedersen, E. R. et al. Associations of plasma kynurenines with risk of acute myocardial infarction in patients with stable angina pectoris. Arterioscler. Thromb. Vasc. Biol. 35, 455\u2013462 (2015).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"408_CR61","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1681\/ASN.2013121283","volume":"26","author":"L Dou","year":"2015","unstructured":"Dou, L. et al. The cardiovascular effect of the uremic solute indole-3 acetic acid. J. Am. Soc. Nephrol. 26, 876\u2013887 (2015).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR62","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/ki.1995.22","volume":"47","author":"RN Foley","year":"1995","unstructured":"Foley, R. N. et al. Clinical and echocardiographic disease in patients starting end-stage renal disease therapy. Kidney Int. 47, 186\u2013192 (1995).","journal-title":"Kidney Int."},{"key":"408_CR63","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.toxlet.2015.01.021","volume":"234","author":"K Yang","year":"2015","unstructured":"Yang, K. et al. Indoxyl sulfate induces oxidative stress and hypertrophy in cardiomyocytes by inhibiting the AMPK\/UCP2 signaling pathway. Toxicol. Lett. 234, 110\u2013119 (2015).","journal-title":"Toxicol. Lett."},{"key":"408_CR64","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1016\/j.lfs.2013.05.008","volume":"92","author":"M Yisireyili","year":"2013","unstructured":"Yisireyili, M. et al. Indoxyl sulfate promotes cardiac fibrosis with enhanced oxidative stress in hypertensive rats. Life Sci. 92, 1180\u20131185 (2013).","journal-title":"Life Sci."},{"key":"408_CR65","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.001852","volume":"4","author":"H Han","year":"2015","unstructured":"Han, H. et al. p-Cresyl sulfate aggravates cardiac dysfunction associated with chronic kidney disease by enhancing apoptosis of cardiomyocytes. J. Am. Heart Assoc. 4, e001852 (2015).","journal-title":"J. Am. Heart Assoc."},{"key":"408_CR66","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.3390\/antiox9111079","volume":"9","author":"J Rysz","year":"2020","unstructured":"Rysz, J., Franczyk, B., Lawinski, J. & Gluba-Brzozka, A. Oxidative stress in ESRD patients on dialysis and the risk of cardiovascular diseases. Antioxidants 9, 1079 (2020).","journal-title":"Antioxidants"},{"key":"408_CR67","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/ki.2009.389","volume":"77","author":"AV Cybulsky","year":"2010","unstructured":"Cybulsky, A. V. Endoplasmic reticulum stress in proteinuric kidney disease. Kidney Int. 77, 187\u2013193 (2010).","journal-title":"Kidney Int."},{"key":"408_CR68","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1111\/j.1523-1755.2004.00399.x","volume":"65","author":"L Dou","year":"2004","unstructured":"Dou, L. et al. The uremic solutes p-cresol and indoxyl sulfate inhibit endothelial proliferation and wound repair. Kidney Int. 65, 442\u2013451 (2004).","journal-title":"Kidney Int."},{"key":"408_CR69","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1053\/j.ajkd.2009.04.022","volume":"54","author":"BK Meijers","year":"2009","unstructured":"Meijers, B. K. et al. The uremic retention solute p-cresyl sulfate and markers of endothelial damage. Am. J. Kidney Dis. 54, 891\u2013901 (2009).","journal-title":"Am. J. Kidney Dis."},{"key":"408_CR70","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1159\/000452604","volume":"41","author":"CJ Lin","year":"2016","unstructured":"Lin, C. J. et al. Indoxyl sulfate impairs endothelial progenitor cells and might contribute to vascular dysfunction in patients with chronic kidney disease. Kidney Blood Press. Res. 41, 1025\u20131036 (2016).","journal-title":"Kidney Blood Press. Res."},{"key":"408_CR71","doi-asserted-by":"publisher","first-page":"S25","DOI":"10.1046\/j.1523-1755.63.s84.9.x","volume":"84","author":"PP De Deyn","year":"2003","unstructured":"De Deyn, P. P., Vanholder, R. & D\u2019Hooge, R. Nitric oxide in uremia: effects of several potentially toxic guanidino compounds. Kidney Int. Suppl. 84, S25\u2013S28 (2003).","journal-title":"Kidney Int. Suppl."},{"key":"408_CR72","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1681\/ASN.2014121241","volume":"27","author":"S Shivanna","year":"2016","unstructured":"Shivanna, S. et al. The aryl hydrocarbon receptor is a critical regulator of tissue factor stability and an antithrombotic target in uremia. J. Am. Soc. Nephrol. 27, 189\u2013201 (2016).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1126\/scitranslmed.aam8475","volume":"9","author":"M Shashar","year":"2017","unstructured":"Shashar, M. et al. Targeting STUB1-tissue factor axis normalizes hyperthrombotic uremic phenotype without increasing bleeding risk. Sci. Transl Med. 9, 1\u201311 (2017).","journal-title":"Sci. Transl Med."},{"key":"408_CR74","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1038\/ki.2013.133","volume":"84","author":"B Gondouin","year":"2013","unstructured":"Gondouin, B. et al. Indolic uremic solutes increase tissue factor production in endothelial cells by the aryl hydrocarbon receptor pathway. Kidney Int. 84, 733\u2013744 (2013).","journal-title":"Kidney Int."},{"key":"408_CR75","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.3389\/fphys.2018.01623","volume":"9","author":"M Karbowska","year":"2018","unstructured":"Karbowska, M. et al. Indoxyl sulfate promotes arterial thrombosis in rat model via increased levels of complex TF\/VII, PAI-1, platelet activation as well as decreased contents of SIRT1 and SIRT3. Front. Physiol. 9, 1623 (2018).","journal-title":"Front. Physiol."},{"key":"408_CR76","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1161\/CIRCULATIONAHA.112.118174","volume":"127","author":"VC Chitalia","year":"2013","unstructured":"Chitalia, V. C. et al. Uremic serum and solutes increase post-vascular interventional thrombotic risk through altered stability of smooth muscle cell tissue factor. Circulation 127, 365\u2013376 (2013).","journal-title":"Circulation"},{"key":"408_CR77","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1681\/ASN.2017080929","volume":"29","author":"VB Kolachalama","year":"2018","unstructured":"Kolachalama, V. B. et al. Uremic solute-aryl hydrocarbon receptor-tissue factor axis associates with thrombosis after vascular injury in humans. J. Am. Soc. Nephrol. 29, 1063\u20131072 (2018).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR78","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1161\/ATVBAHA.110.220202","volume":"31","author":"D Wu","year":"2011","unstructured":"Wu, D. et al. Activation of aryl hydrocarbon receptor induces vascular inflammation and promotes atherosclerosis in apolipoprotein E\u2212\/\u2212 mice. Arterioscler. Thromb. Vasc. Biol. 31, 1260\u20131267 (2011).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"408_CR79","doi-asserted-by":"publisher","first-page":"218","DOI":"10.3390\/toxins10060218","volume":"10","author":"L Henaut","year":"2018","unstructured":"Henaut, L., Mary, A., Chillon, J. M., Kamel, S. & Massy, Z. A. The impact of uremic toxins on vascular smooth muscle cell function. Toxins 10, 218 (2018).","journal-title":"Toxins"},{"key":"408_CR80","doi-asserted-by":"publisher","first-page":"2667","DOI":"10.1182\/blood-2016-10-744060","volume":"129","author":"K Yang","year":"2017","unstructured":"Yang, K. et al. Indoxyl sulfate induces platelet hyperactivity and contributes to chronic kidney disease-associated thrombosis in mice. Blood 129, 2667\u20132679 (2017).","journal-title":"Blood"},{"key":"408_CR81","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3390\/toxins9070229","volume":"9","author":"M Karbowska","year":"2017","unstructured":"Karbowska, M. et al. The uremic toxin indoxyl sulfate accelerates thrombotic response after vascular injury in animal models. Toxins 9, 229 (2017).","journal-title":"Toxins"},{"key":"408_CR82","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/s41581-018-0101-8","volume":"15","author":"X Wang","year":"2019","unstructured":"Wang, X. & Shapiro, J. I. Evolving concepts in the pathogenesis of uraemic cardiomyopathy. Nat. Rev. Nephrol. 15, 159\u2013175 (2019).","journal-title":"Nat. Rev. Nephrol."},{"key":"408_CR83","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0147159","volume":"11","author":"S Eloot","year":"2016","unstructured":"Eloot, S. et al. Protein-bound uremic toxin profiling as a tool to optimize hemodialysis. PLoS ONE 11, e0147159 (2016).","journal-title":"PLoS ONE"},{"key":"408_CR84","doi-asserted-by":"publisher","first-page":"358","DOI":"10.3390\/toxins8120358","volume":"8","author":"SC Leong","year":"2016","unstructured":"Leong, S. C. & Sirich, T. L. Indoxyl sulfate-review of toxicity and therapeutic strategies. Toxins 8, 358 (2016).","journal-title":"Toxins"},{"key":"408_CR85","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3390\/toxins9020052","volume":"9","author":"T Gryp","year":"2017","unstructured":"Gryp, T., Vanholder, R., Vaneechoutte, M. & Glorieux, G. p-Cresyl Sulfate. Toxins 9, 52 (2017).","journal-title":"Toxins"},{"key":"408_CR86","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.2215\/CJN.03980609","volume":"4","author":"FC Barreto","year":"2009","unstructured":"Barreto, F. C. et al. Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients. Clin. J. Am. Soc. Nephrol. 4, 1551\u20131558 (2009).","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"408_CR87","doi-asserted-by":"publisher","first-page":"117864691769460","DOI":"10.1177\/1178646917694600","volume":"10","author":"S Debnath","year":"2017","unstructured":"Debnath, S. et al. Tryptophan metabolism in patients with chronic kidney disease secondary to type 2 diabetes: relationship to inflammatory markers. Int. J. Tryptophan Res. 10, 1178646917694600 (2017).","journal-title":"Int. J. Tryptophan Res."},{"key":"408_CR88","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1681\/ASN.2014121241","volume":"27","author":"S Shivanna","year":"2016","unstructured":"Shivanna, S. et al. The aryl hydrocarbon receptor is a critical regulator of tissue factor stability and an antithrombotic target in uremia. J. Am. Soc. Nephrol. 27, 187\u2013201 (2016).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR89","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1016\/j.semnephrol.2014.02.001","volume":"34","author":"R Vanholder","year":"2014","unstructured":"Vanholder, R. & Glorieux, G. Introduction: uremic toxicity \u2014 state of the art 2014. Semin. Nephrol. 34, 85\u201386 (2014).","journal-title":"Semin. Nephrol."},{"key":"408_CR90","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1681\/ASN.2013101062","volume":"25","author":"R Vanholder","year":"2014","unstructured":"Vanholder, R., Schepers, E., Pletinck, A., Nagler, E. V. & Glorieux, G. The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: a systematic review. J. Am. Soc. Nephrol. 25, 1897\u20131907 (2014).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR91","doi-asserted-by":"publisher","first-page":"412","DOI":"10.3390\/toxins10100412","volume":"10","author":"T Addi","year":"2018","unstructured":"Addi, T., Dou, L. & Burtey, S. Tryptophan-derived uremic toxins and thrombosis in chronic kidney disease. Toxins 10, 412 (2018).","journal-title":"Toxins"},{"key":"408_CR92","doi-asserted-by":"publisher","first-page":"883","DOI":"10.2174\/1389200219666180427164731","volume":"19","author":"P Konopelski","year":"2018","unstructured":"Konopelski, P. & Ufnal, M. Indoles \u2014 gut bacteria metabolites of tryptophan with pharmacotherapeutic potential. Curr. Drug Metab. 19, 883\u2013890 (2018).","journal-title":"Curr. Drug Metab."},{"key":"408_CR93","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s12882-016-0283-x","volume":"17","author":"WE Mitch","year":"2016","unstructured":"Mitch, W. E. & Remuzzi, G. Diets for patients with chronic kidney disease, should we reconsider? BMC Nephrol. 17, 80 (2016).","journal-title":"BMC Nephrol."},{"key":"408_CR94","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/s41581-020-0297-2","volume":"16","author":"JJ Carrero","year":"2020","unstructured":"Carrero, J. J. et al. Plant-based diets to manage the risks and complications of chronic kidney disease. Nat. Rev. Nephrol. 16, 525\u2013542 (2020).","journal-title":"Nat. Rev. Nephrol."},{"key":"408_CR95","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1053\/j.ajkd.2007.02.278","volume":"49","author":"G Brunori","year":"2007","unstructured":"Brunori, G. et al. Efficacy and safety of a very-low-protein diet when postponing dialysis in the elderly: a prospective randomized multicenter controlled study. Am. J. Kidney Dis. 49, 569\u2013580 (2007).","journal-title":"Am. J. Kidney Dis."},{"key":"408_CR96","first-page":"CD001892","volume":"2","author":"D Fouque","year":"2000","unstructured":"Fouque, D., Wang, P., Laville, M. & Boissel, J. P. Low protein diets delay end-stage renal disease in non diabetic adults with chronic renal failure. Cochrane Database Syst. Rev. 2,CD001892 (2000).","journal-title":"Cochrane Database Syst. Rev."},{"key":"408_CR97","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0140820","volume":"10","author":"R Poesen","year":"2015","unstructured":"Poesen, R. et al. The influence of dietary protein intake on mammalian tryptophan and phenolic metabolites. PLoS ONE 10, e0140820 (2015).","journal-title":"PLoS ONE"},{"key":"408_CR98","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1002\/jcsm.12264","volume":"9","author":"CM Rhee","year":"2018","unstructured":"Rhee, C. M., Ahmadi, S. F., Kovesdy, C. P. & Kalantar-Zadeh, K. Low-protein diet for conservative management of chronic kidney disease: a systematic review and meta-analysis of controlled trials. J. Cachexia Sarcopenia Muscle 9, 235\u2013245 (2018).","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"408_CR99","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1053\/j.ajkd.2008.08.009","volume":"53","author":"V Menon","year":"2009","unstructured":"Menon, V. et al. Effect of a very low-protein diet on outcomes: long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study. Am. J. Kidney Dis. 53, 208\u2013217 (2009).","journal-title":"Am. J. Kidney Dis."},{"key":"408_CR100","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1053\/j.ajkd.2006.08.023","volume":"48","author":"AS Levey","year":"2006","unstructured":"Levey, A. S. et al. Effect of dietary protein restriction on the progression of kidney disease: long-term follow-up of the Modification of Diet in Renal Disease (MDRD) Study. Am. J. Kidney Dis. 48, 879\u2013888 (2006).","journal-title":"Am. J. Kidney Dis."},{"key":"408_CR101","doi-asserted-by":"publisher","first-page":"957","DOI":"10.3390\/nu11050957","volume":"11","author":"A Li","year":"2019","unstructured":"Li, A., Lee, H. Y. & Lin, Y. C. The effect of ketoanalogues on chronic kidney disease deterioration: a meta-analysis. Nutrients 11, 957 (2019).","journal-title":"Nutrients"},{"key":"408_CR102","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/ki.1990.178","volume":"38","author":"P Kontessis","year":"1990","unstructured":"Kontessis, P. et al. Renal, metabolic and hormonal responses to ingestion of animal and vegetable proteins. Kidney Int. 38, 136\u2013144 (1990).","journal-title":"Kidney Int."},{"key":"408_CR103","doi-asserted-by":"publisher","first-page":"648","DOI":"10.2337\/dc07-2065","volume":"31","author":"L Azadbakht","year":"2008","unstructured":"Azadbakht, L., Atabak, S. & Esmaillzadeh, A. Soy protein intake, cardiorenal indices, and C-reactive protein in type 2 diabetes with nephropathy: a longitudinal randomized clinical trial. Diabetes Care 31, 648\u2013654 (2008).","journal-title":"Diabetes Care"},{"key":"408_CR104","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.1128\/AEM.66.4.1654-1661.2000","volume":"66","author":"A Barcenilla","year":"2000","unstructured":"Barcenilla, A. et al. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl. Env. Microbiol. 66, 1654\u20131661 (2000).","journal-title":"Appl. Env. Microbiol."},{"key":"408_CR105","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1126\/science.1223813","volume":"336","author":"JK Nicholson","year":"2012","unstructured":"Nicholson, J. K. et al. Host-gut microbiota metabolic interactions. Science 336, 1262\u20131267 (2012).","journal-title":"Science"},{"key":"408_CR106","doi-asserted-by":"publisher","first-page":"779","DOI":"10.3390\/nu10060779","volume":"10","author":"M Pignanelli","year":"2018","unstructured":"Pignanelli, M. et al. Mediterranean diet score: associations with metabolic products of the intestinal microbiome, carotid plaque burden, and renal function. Nutrients 10, 779 (2018).","journal-title":"Nutrients"},{"key":"408_CR107","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1016\/j.nutres.2015.07.002","volume":"35","author":"NE Boutagy","year":"2015","unstructured":"Boutagy, N. E. et al. Short-term high-fat diet increases postprandial trimethylamine-N-oxide in humans. Nutr. Res. 35, 858\u2013864 (2015).","journal-title":"Nutr. Res."},{"key":"408_CR108","doi-asserted-by":"publisher","first-page":"350","DOI":"10.3389\/fphys.2017.00350","volume":"8","author":"T Li","year":"2017","unstructured":"Li, T., Chen, Y., Gua, C. & Li, X. Elevated circulating trimethylamine N-oxide levels contribute to endothelial dysfunction in aged rats through vascular inflammation and oxidative stress. Front. Physiol. 8, 350 (2017).","journal-title":"Front. Physiol."},{"key":"408_CR109","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.cmet.2014.10.006","volume":"20","author":"RA Koeth","year":"2014","unstructured":"Koeth, R. A. et al. gamma-Butyrobetaine is a proatherogenic intermediate in gut microbial metabolism of L-carnitine to TMAO. Cell Metab. 20, 799\u2013812 (2014).","journal-title":"Cell Metab."},{"key":"408_CR110","doi-asserted-by":"publisher","first-page":"1398","DOI":"10.3390\/nu10101398","volume":"10","author":"MH Janeiro","year":"2018","unstructured":"Janeiro, M. H., Ramirez, M. J., Milagro, F. I., Martinez, J. A. & Solas, M. Implication of trimethylamine N-oxide (TMAO) in disease: potential biomarker or new therapeutic target. Nutrients 10, 1398 (2018).","journal-title":"Nutrients"},{"key":"408_CR111","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1800389","volume":"378","author":"R Estruch","year":"2018","unstructured":"Estruch, R. et al. Primary prevention of cardiovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N. Engl. J. Med. 378, e34 (2018).","journal-title":"N. Engl. J. Med."},{"key":"408_CR112","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/j.jff.2015.04.001","volume":"15","author":"Wei-Kai Wu","year":"2015","unstructured":"Wu, Wei-Kai, Chi-Tang Hoc, S. P., Kuod, Ching-Hua, Wub, Ming-Shiang & Shee, Lee-Yan Dietary allicin reduces transformation of L-carnitine to TMAO through impact on gut microbiota. J. Funct. Foods 15, 408\u2013417 (2015).","journal-title":"J. Funct. Foods"},{"key":"408_CR113","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1002\/ptr.4796","volume":"27","author":"JY Chan","year":"2013","unstructured":"Chan, J. Y., Yuen, A. C., Chan, R. Y. & Chan, S. W. A review of the cardiovascular benefits and antioxidant properties of allicin. Phytother. Res. 27, 637\u2013646 (2013).","journal-title":"Phytother. Res."},{"key":"408_CR114","doi-asserted-by":"publisher","first-page":"2909","DOI":"10.3390\/nu11122909","volume":"11","author":"X Shi","year":"2019","unstructured":"Shi, X. et al. Allicin improves metabolism in high-fat diet-induced obese mice by modulating the gut microbiota. Nutrients 11, 2909 (2019).","journal-title":"Nutrients"},{"key":"408_CR115","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1016\/j.cell.2015.11.055","volume":"163","author":"Z Wang","year":"2015","unstructured":"Wang, Z. et al. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell 163, 1585\u20131595 (2015).","journal-title":"Cell"},{"key":"408_CR116","doi-asserted-by":"publisher","first-page":"139","DOI":"10.3389\/fphys.2017.00139","volume":"8","author":"K Chen","year":"2017","unstructured":"Chen, K., Zheng, X., Feng, M., Li, D. & Zhang, H. Gut microbiota-dependent metabolite trimethylamine N-oxide contributes to cardiac dysfunction in western diet-induced obese mice. Front. Physiol. 8, 139 (2017).","journal-title":"Front. Physiol."},{"key":"408_CR117","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1172\/JCI94601","volume":"129","author":"RA Koeth","year":"2019","unstructured":"Koeth, R. A. et al. l-Carnitine in omnivorous diets induces an atherogenic gut microbial pathway in humans. J. Clin. Invest. 129, 373\u2013387 (2019).","journal-title":"J. Clin. Invest."},{"key":"408_CR118","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3390\/nu7010017","volume":"7","author":"MA Conlon","year":"2014","unstructured":"Conlon, M. A. & Bird, A. R. The impact of diet and lifestyle on gut microbiota and human health. Nutrients 7, 17\u201344 (2014).","journal-title":"Nutrients"},{"key":"408_CR119","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1161\/CIRCRESAHA.116.309006","volume":"120","author":"MM Santisteban","year":"2017","unstructured":"Santisteban, M. M. et al. Hypertension-linked pathophysiological alterations in the gut. Circ. Res. 120, 312\u2013323 (2017).","journal-title":"Circ. Res."},{"key":"408_CR120","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00900-1","volume":"8","author":"Z Jie","year":"2017","unstructured":"Jie, Z. et al. The gut microbiome in atherosclerotic cardiovascular disease. Nat. Commun. 8, 845 (2017).","journal-title":"Nat. Commun."},{"key":"408_CR121","doi-asserted-by":"publisher","first-page":"1906","DOI":"10.1136\/gutjnl-2016-312297","volume":"65","author":"G Ianiro","year":"2016","unstructured":"Ianiro, G., Tilg, H. & Gasbarrini, A. Antibiotics as deep modulators of gut microbiota: between good and evil. Gut 65, 1906\u20131915 (2016).","journal-title":"Gut"},{"key":"408_CR122","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1681\/ASN.2015111285","volume":"28","author":"K Andersen","year":"2017","unstructured":"Andersen, K. et al. Intestinal dysbiosis, barrier dysfunction, and bacterial translocation account for CKD-related systemic inflammation. J. Am. Soc. Nephrol. 28, 76\u201383 (2017).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR123","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1159\/000360010","volume":"39","author":"J Wong","year":"2014","unstructured":"Wong, J. et al. Expansion of urease- and uricase-containing, indole- and p-cresol-forming and contraction of short-chain fatty acid-producing intestinal microbiota in ESRD. Am. J. Nephrol. 39, 230\u2013237 (2014).","journal-title":"Am. J. Nephrol."},{"key":"408_CR124","doi-asserted-by":"publisher","first-page":"2788","DOI":"10.1093\/ndt\/gfl273","volume":"21","author":"S Goncalves","year":"2006","unstructured":"Goncalves, S. et al. Associations between renal function, volume status and endotoxaemia in chronic kidney disease patients. Nephrol. Dial. Transpl. 21, 2788\u20132794 (2006).","journal-title":"Nephrol. Dial. Transpl."},{"key":"408_CR125","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/ki.1973.79","volume":"4","author":"L Raij","year":"1973","unstructured":"Raij, L., Shapiro, F. L. & Michael, A. F. Endotoxemia in febrile reactions during hemodialysis. Kidney Int. 4, 57\u201360 (1973).","journal-title":"Kidney Int."},{"key":"408_CR126","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1038\/s41581-019-0172-1","volume":"15","author":"B Meijers","year":"2019","unstructured":"Meijers, B., Evenepoel, P. & Anders, H. J. Intestinal microbiome and fitness in kidney disease. Nat. Rev. Nephrol. 15, 531\u2013545 (2019).","journal-title":"Nat. Rev. Nephrol."},{"key":"408_CR127","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/s41581-020-00345-8","volume":"17","author":"D Mafra","year":"2021","unstructured":"Mafra, D. et al. Food as medicine: targeting the uraemic phenotype in chronic kidney disease. Nature Rev. Nephrol. 17, 153\u2013171 (2021).","journal-title":"Nature Rev. Nephrol."},{"key":"408_CR128","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1053\/j.jrn.2014.09.002","volume":"25","author":"YA Salmean","year":"2015","unstructured":"Salmean, Y. A., Segal, M. S., Palii, S. P. & Dahl, W. J. Fiber supplementation lowers plasma p-cresol in chronic kidney disease patients. J. Ren. Nutr. 25, 316\u2013320 (2015).","journal-title":"J. Ren. Nutr."},{"key":"408_CR129","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1038\/sj.ki.5001523","volume":"70","author":"P Evenepoel","year":"2006","unstructured":"Evenepoel, 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 Int. 70, 192\u2013198 (2006).","journal-title":"Kidney Int."},{"key":"408_CR130","doi-asserted-by":"publisher","first-page":"F824","DOI":"10.1152\/ajprenal.00314.2017","volume":"315","author":"E Mishima","year":"2018","unstructured":"Mishima, E. et al. Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model. Am. J. Physiol. Renal Physiol. 315, F824\u2013F833 (2018).","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"408_CR131","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1161\/CIRCULATIONAHA.116.024545","volume":"135","author":"FZ Marques","year":"2017","unstructured":"Marques, F. Z. et al. High-fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in hypertensive mice. Circulation 135, 964\u2013977 (2017).","journal-title":"Circulation"},{"key":"408_CR132","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/nature24628","volume":"551","author":"N Wilck","year":"2017","unstructured":"Wilck, N. et al. Salt-responsive gut commensal modulates TH17 axis and disease. Nature 551, 585\u2013589 (2017).","journal-title":"Nature"},{"key":"408_CR133","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1053\/j.jrn.2017.06.010","volume":"28","author":"NA Borges","year":"2018","unstructured":"Borges, N. A. et al. Probiotic supplementation in chronic kidney disease: a double-blind, randomized, placebo-controlled trial. J. Ren. Nutr. 28, 28\u201336 (2018).","journal-title":"J. Ren. Nutr."},{"key":"408_CR134","doi-asserted-by":"publisher","first-page":"223","DOI":"10.2215\/CJN.05240515","volume":"11","author":"M Rossi","year":"2016","unstructured":"Rossi, M. et al. Synbiotics easing renal failure by improving gut microbiology (SYNERGY): a randomized trial. Clin. J. Am. Soc. Nephrol. 11, 223\u2013231 (2016).","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"408_CR135","unstructured":"US National Library of Medicine. ClinicalTrials.gov https:\/\/clinicaltrials.gov\/ct2\/show\/NCT02302287 (2016)."},{"key":"408_CR136","doi-asserted-by":"publisher","first-page":"9217","DOI":"10.1007\/s00253-019-10142-4","volume":"103","author":"AU Din","year":"2019","unstructured":"Din, A. U. et al. Amelioration of TMAO through probiotics and its potential role in atherosclerosis. Appl. Microbiol. Biotechnol. 103, 9217\u20139228 (2019).","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"408_CR137","doi-asserted-by":"publisher","first-page":"2357","DOI":"10.1002\/oby.21212","volume":"23","author":"NE Boutagy","year":"2015","unstructured":"Boutagy, N. E. et al. Probiotic supplementation and trimethylamine-N-oxide production following a high-fat diet. Obesity 23, 2357\u20132363 (2015).","journal-title":"Obesity"},{"key":"408_CR138","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.kint.2017.01.003","volume":"91","author":"R Yacoub","year":"2017","unstructured":"Yacoub, R. & Wyatt, C. M. Manipulating the gut microbiome to decrease uremic toxins. Kidney Int. 91, 521\u2013523 (2017).","journal-title":"Kidney Int."},{"key":"408_CR139","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/j.chom.2016.10.021","volume":"20","author":"AS Devlin","year":"2016","unstructured":"Devlin, A. S. et al. Modulation of a circulating uremic solute via rational genetic manipulation of the gut microbiota. Cell Host Microbe 20, 709\u2013715 (2016).","journal-title":"Cell Host Microbe"},{"key":"408_CR140","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1038\/s41591-018-0128-1","volume":"24","author":"AB Roberts","year":"2018","unstructured":"Roberts, A. B. et al. Development of a gut microbe-targeted nonlethal therapeutic to inhibit thrombosis potential. Nat. Med. 24, 1407\u20131417 (2018).","journal-title":"Nat. Med."},{"key":"408_CR141","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.chom.2019.07.002","volume":"26","author":"DA Colosimo","year":"2019","unstructured":"Colosimo, D. A. et al. Mapping interactions of microbial metabolites with human G-protein-coupled receptors. Cell Host Microbe 26, 273\u2013282.e7 (2019).","journal-title":"Cell Host Microbe"},{"key":"408_CR142","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1038\/nature06245","volume":"449","author":"L Dethlefsen","year":"2007","unstructured":"Dethlefsen, L., McFall-Ngai, M. & Relman, D. A. An ecological and evolutionary perspective on human-microbe mutualism and disease. Nature 449, 811\u2013818 (2007).","journal-title":"Nature"},{"key":"408_CR143","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1016\/j.kint.2020.01.028","volume":"97","author":"T Gryp","year":"2020","unstructured":"Gryp, T. 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. 97, 1230\u20131242 (2020).","journal-title":"Kidney Int."},{"key":"408_CR144","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.bpc.2010.03.001","volume":"148","author":"P Ascenzi","year":"2010","unstructured":"Ascenzi, P. & Fasano, M. Allostery in a monomeric protein: the case of human serum albumin. Biophys. Chem. 148, 16\u201322 (2010).","journal-title":"Biophys. Chem."},{"key":"408_CR145","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1016\/S0006-2952(02)00869-9","volume":"63","author":"VV Sarnatskaya","year":"2002","unstructured":"Sarnatskaya, V. V. et al. Effect of protein-bound uraemic toxins on the thermodynamic characteristics of human albumin. Biochem. Pharmacol. 63, 1287\u20131296 (2002).","journal-title":"Biochem. Pharmacol."},{"key":"408_CR146","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1053\/j.ajkd.2007.12.035","volume":"51","author":"BK Meijers","year":"2008","unstructured":"Meijers, B. K., Bammens, B., Verbeke, K. & Evenepoel, P. A review of albumin binding in CKD. Am. J. Kidney Dis. 51, 839\u2013850 (2008).","journal-title":"Am. J. Kidney Dis."},{"key":"408_CR147","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0071422","volume":"8","author":"N Zaidi","year":"2013","unstructured":"Zaidi, N., Ajmal, M. R., Rabbani, G., Ahmad, E. & Khan, R. H. A comprehensive insight into binding of hippuric acid to human serum albumin: a study to uncover its impaired elimination through hemodialysis. PLoS ONE 8, e71422 (2013).","journal-title":"PLoS ONE"},{"key":"408_CR148","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jmb.2005.07.075","volume":"353","author":"J Ghuman","year":"2005","unstructured":"Ghuman, J. et al. Structural basis of the drug-binding specificity of human serum albumin. J. Mol. Biol. 353, 38\u201352 (2005).","journal-title":"J. Mol. Biol."},{"key":"408_CR149","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1053\/j.jrn.2011.10.011","volume":"22","author":"TW Meyer","year":"2012","unstructured":"Meyer, T. W. The removal of protein-bound solutes by dialysis. J. Ren. Nutr. 22, 203\u2013206 (2012).","journal-title":"J. Ren. Nutr."},{"key":"408_CR150","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1093\/ndt\/gfp437","volume":"25","author":"DH Krieter","year":"2010","unstructured":"Krieter, D. H. et al. Protein-bound uraemic toxin removal in haemodialysis and post-dilution haemodiafiltration. Nephrol. Dial. Transpl. 25, 212\u2013218 (2010).","journal-title":"Nephrol. Dial. Transpl."},{"key":"408_CR151","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1159\/000350843","volume":"35","author":"T Niwa","year":"2013","unstructured":"Niwa, T. Removal of protein-bound uraemic toxins by haemodialysis. Blood Purif. 35, 20\u201325 (2013).","journal-title":"Blood Purif."},{"key":"408_CR152","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1111\/j.1600-6143.2007.01909.x","volume":"7","author":"BK Meijers","year":"2007","unstructured":"Meijers, B. K. et al. Major coagulation disturbances during fractionated plasma separation and adsorption. Am. J. Transpl. 7, 2195\u20132199 (2007).","journal-title":"Am. J. Transpl."},{"key":"408_CR153","doi-asserted-by":"publisher","DOI":"10.1038\/srep23389","volume":"6","author":"X Tao","year":"2016","unstructured":"Tao, X. et al. Improved dialytic removal of protein-bound uraemic toxins with use of albumin binding competitors: an in vitro human whole blood study. Sci. Rep. 6, 23389 (2016).","journal-title":"Sci. Rep."},{"key":"408_CR154","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1681\/ASN.2018111150","volume":"30","author":"Y Sakaguchi","year":"2019","unstructured":"Sakaguchi, Y. et al. A randomized trial of magnesium oxide and oral carbon adsorbent for coronary artery calcification in predialysis CKD. J. Am. Soc. Nephrol. 30, 1073\u20131085 (2019).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR155","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1038\/s41581-018-0078-3","volume":"15","author":"OM Kuro","year":"2019","unstructured":"Kuro, O. M. The Klotho proteins in health and disease. Nat. Rev. Nephrol. 15, 27\u201344 (2019).","journal-title":"Nat. Rev. Nephrol."},{"key":"408_CR156","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1161\/HYPERTENSIONAHA.117.10560","volume":"71","author":"J Chen","year":"2018","unstructured":"Chen, J., Fan, J., Wang, S. & Sun, Z. Secreted klotho attenuates inflammation-associated aortic valve fibrosis in senescence-accelerated mice P1. Hypertension 71, 877\u2013885 (2018).","journal-title":"Hypertension"},{"key":"408_CR157","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07253-3","volume":"9","author":"A Sahu","year":"2018","unstructured":"Sahu, A. et al. Age-related declines in alpha-Klotho drive progenitor cell mitochondrial dysfunction and impaired muscle regeneration. Nat. Commun. 9, 4859 (2018).","journal-title":"Nat. Commun."},{"key":"408_CR158","doi-asserted-by":"publisher","first-page":"1615","DOI":"10.1002\/stem.2305","volume":"34","author":"J Fan","year":"2016","unstructured":"Fan, J. & Sun, Z. The antiaging gene Klotho regulates proliferation and differentiation of adipose-derived stem cells. Stem Cell 34, 1615\u20131625 (2016).","journal-title":"Stem Cell"},{"key":"408_CR159","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1681\/ASN.2009121311","volume":"22","author":"MC Hu","year":"2011","unstructured":"Hu, M. C. et al. Klotho deficiency causes vascular calcification in chronic kidney disease. J. Am. Soc. Nephrol. 22, 124\u2013136 (2011).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR160","doi-asserted-by":"publisher","first-page":"872193","DOI":"10.1155\/2015\/872193","volume":"2015","author":"S Rotondi","year":"2015","unstructured":"Rotondi, S. et al. Soluble alpha-klotho serum levels in chronic kidney disease. Int. J. Endocrinol. 2015, 872193 (2015).","journal-title":"Int. J. Endocrinol."},{"key":"408_CR161","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1038\/ki.2011.445","volume":"81","author":"CY Sun","year":"2012","unstructured":"Sun, C. Y., Chang, S. C. & Wu, M. S. Suppression of Klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation. Kidney Int. 81, 640\u2013650 (2012).","journal-title":"Kidney Int."},{"key":"408_CR162","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1016\/j.kint.2016.10.034","volume":"91","author":"MC Hu","year":"2017","unstructured":"Hu, M. C. et al. Recombinant alpha-Klotho may be prophylactic and therapeutic for acute to chronic kidney disease progression and uremic cardiomyopathy. Kidney Int. 91, 1104\u20131114 (2017).","journal-title":"Kidney Int."},{"key":"408_CR163","doi-asserted-by":"publisher","first-page":"2434","DOI":"10.1681\/ASN.2014060543","volume":"26","author":"K Yang","year":"2015","unstructured":"Yang, K. et al. Klotho protects against indoxyl sulphate-induced myocardial hypertrophy. J. Am. Soc. Nephrol. 26, 2434\u20132446 (2015).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR164","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056695","volume":"8","author":"M Kitagawa","year":"2013","unstructured":"Kitagawa, M. et al. A decreased level of serum soluble Klotho is an independent biomarker associated with arterial stiffness in patients with chronic kidney disease. PLoS ONE 8, e56695 (2013).","journal-title":"PLoS ONE"},{"key":"408_CR165","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.2215\/CJN.07870713","volume":"9","author":"S Seiler","year":"2014","unstructured":"Seiler, S. et al. Associations of FGF-23 and sKlotho with cardiovascular outcomes among patients with CKD stages 2\u20134. Clin. J. Am. Soc. Nephrol. 9, 1049\u20131058 (2014).","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"408_CR166","unstructured":"US National Library of Medicine. ClinicalTrials.gov https:\/\/clinicaltrials.gov\/ct2\/show\/NCT03996746 (2020)."},{"key":"408_CR167","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.taap.2005.07.005","volume":"212","author":"AK Lund","year":"2006","unstructured":"Lund, A. K., Goens, M. B., Nunez, B. A. & Walker, M. K. Characterizing the role of endothelin-1 in the progression of cardiac hypertrophy in aryl hydrocarbon receptor (AhR) null mice. Toxicol. Appl. Pharmacol. 212, 127\u2013135 (2006).","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"408_CR168","doi-asserted-by":"publisher","first-page":"2896","DOI":"10.1074\/jbc.M110.187534","volume":"286","author":"V Sauzeau","year":"2011","unstructured":"Sauzeau, V. et al. Transcriptional factor aryl hydrocarbon receptor (Ahr) controls cardiovascular and respiratory functions by regulating the expression of the Vav3 proto-oncogene. J. Biol. Chem. 286, 2896\u20132909 (2011).","journal-title":"J. Biol. Chem."},{"key":"408_CR169","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejphar.2005.11.023","volume":"530","author":"SH Juan","year":"2006","unstructured":"Juan, S. H., Lee, J. L., Ho, P. Y., Lee, Y. H. & Lee, W. S. Antiproliferative and antiangiogenic effects of 3-methylcholanthrene, an aryl-hydrocarbon receptor agonist, in human umbilical vascular endothelial cells. Eur. J. Pharmacol. 530, 1\u20138 (2006).","journal-title":"Eur. J. Pharmacol."},{"key":"408_CR170","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1161\/ATVBAHA.106.138701","volume":"27","author":"S Ichihara","year":"2007","unstructured":"Ichihara, S. et al. A role for the aryl hydrocarbon receptor in regulation of ischemia-induced angiogenesis. Arterioscler. Thromb. Vasc. Biol. 27, 1297\u20131304 (2007).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"408_CR171","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1385\/CT:3:2:153","volume":"3","author":"A Vasquez","year":"2003","unstructured":"Vasquez, A. et al. A role for the aryl hydrocarbon receptor in cardiac physiology and function as demonstrated by AhR knockout mice. Cardiovasc. Toxicol. 3, 153\u2013163 (2003).","journal-title":"Cardiovasc. Toxicol."},{"key":"408_CR172","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.bcp.2011.06.011","volume":"82","author":"LN Agbor","year":"2011","unstructured":"Agbor, L. N., Elased, K. M. & Walker, M. K. Endothelial cell-specific aryl hydrocarbon receptor knockout mice exhibit hypotension mediated, in part, by an attenuated angiotensin II responsiveness. Biochem. Pharmacol. 82, 514\u2013523 (2011).","journal-title":"Biochem. Pharmacol."},{"key":"408_CR173","doi-asserted-by":"publisher","first-page":"1756","DOI":"10.1111\/jphp.12484","volume":"67","author":"Y Xue","year":"2015","unstructured":"Xue, Y. et al. Baicalin inhibits inflammation and attenuates myocardial ischaemic injury by aryl hydrocarbon receptor. J. Pharm. Pharmacol. 67, 1756\u20131764 (2015).","journal-title":"J. Pharm. Pharmacol."},{"key":"408_CR174","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1021\/bi901786x","volume":"49","author":"JC Schroeder","year":"2010","unstructured":"Schroeder, J. C. et al. The uremic toxin 3-indoxyl sulfate is a potent endogenous agonist for the human aryl hydrocarbon receptor. Biochemistry 49, 393\u2013400 (2010).","journal-title":"Biochemistry"},{"key":"408_CR175","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1016\/j.kint.2017.11.010","volume":"93","author":"L Dou","year":"2018","unstructured":"Dou, L. et al. Aryl hydrocarbon receptor is activated in patients and mice with chronic kidney disease. Kidney Int. 93, 986\u2013999 (2018).","journal-title":"Kidney Int."},{"key":"408_CR176","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.kint.2019.09.029","volume":"97","author":"JA Walker","year":"2020","unstructured":"Walker, J. A. et al. Temporal and tissue-specific activation of aryl hydrocarbon receptor in discrete mouse models of kidney disease. Kidney Int. 97, 538\u2013550 (2020).","journal-title":"Kidney Int."},{"key":"408_CR177","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1379\/1466-1268(2003)008<0303:CALBTC>2.0.CO;2","volume":"8","author":"H McDonough","year":"2003","unstructured":"McDonough, H. & Patterson, C. CHIP: a link between the chaperone and proteasome systems. Cell Stress Chaperones 8, 303\u2013308 (2003).","journal-title":"Cell Stress Chaperones"},{"key":"408_CR178","doi-asserted-by":"publisher","DOI":"10.1038\/srep07095","volume":"4","author":"H Hiyoshi","year":"2014","unstructured":"Hiyoshi, H. et al. 2-(4-Hydroxy-3-methoxyphenyl)-benzothiazole suppresses tumor progression and metastatic potential of breast cancer cells by inducing ubiquitin ligase CHIP. Sci. Rep. 4, 7095 (2014).","journal-title":"Sci. Rep."},{"key":"408_CR179","doi-asserted-by":"publisher","first-page":"2249","DOI":"10.1016\/j.jacc.2006.12.049","volume":"49","author":"KA Fox","year":"2007","unstructured":"Fox, K. A. et al. The impact of renal dysfunction on outcomes in the ExTRACT-TIMI 25 trial. J. Am. Coll. Cardiol. 49, 2249\u20132255 (2007).","journal-title":"J. Am. Coll. Cardiol."},{"key":"408_CR180","doi-asserted-by":"publisher","first-page":"119","DOI":"10.4255\/mcpharmacol.09.15","volume":"1","author":"CA Flaveny","year":"2009","unstructured":"Flaveny, C. A. & Perdew, G. H. Transgenic humanized AHR mouse reveals differences between human and mouse AHR ligand selectivity. Mol. Cell Pharmacol. 1, 119\u2013123 (2009).","journal-title":"Mol. Cell Pharmacol."},{"key":"408_CR181","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1093\/toxsci\/kfp308","volume":"114","author":"CA Flaveny","year":"2010","unstructured":"Flaveny, C. A., Murray, I. A. & Perdew, G. H. Differential gene regulation by the human and mouse aryl hydrocarbon receptor. Toxicol. Sci. 114, 217\u2013225 (2010).","journal-title":"Toxicol. Sci."},{"key":"408_CR182","doi-asserted-by":"publisher","first-page":"6127","DOI":"10.1128\/MCB.00323-07","volume":"27","author":"X Chang","year":"2007","unstructured":"Chang, X. et al. Ligand-independent regulation of transforming growth factor beta1 expression and cell cycle progression by the aryl hydrocarbon receptor. Mol. Cell Biol. 27, 6127\u20136139 (2007).","journal-title":"Mol. Cell Biol."},{"key":"408_CR183","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1093\/toxsci\/kfn149","volume":"106","author":"MK Bunger","year":"2008","unstructured":"Bunger, M. K. et al. Abnormal liver development and resistance to 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in mice carrying a mutation in the DNA-binding domain of the aryl hydrocarbon receptor. Toxicol. Sci. 106, 83\u201392 (2008).","journal-title":"Toxicol. Sci."},{"key":"408_CR184","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1111\/jth.12490","volume":"12","author":"S Lindsey","year":"2014","unstructured":"Lindsey, S., Jiang, J., Woulfe, D. & Papoutsakis, E. T. Platelets from mice lacking the aryl hydrocarbon receptor exhibit defective collagen-dependent signaling. J. Thromb. Haemost. 12, 383\u2013394 (2014).","journal-title":"J. Thromb. Haemost."},{"key":"408_CR185","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.bbrc.2005.08.162","volume":"338","author":"Y Fujii-Kuriyama","year":"2005","unstructured":"Fujii-Kuriyama, Y. & Mimura, J. Molecular mechanisms of AhR functions in the regulation of cytochrome P450 genes. Biochem. Biophys. Res. Commun. 338, 311\u2013317 (2005).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"408_CR186","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3390\/toxins11040209","volume":"11","author":"T Santana Machado","year":"2019","unstructured":"Santana Machado, T., Cerini, C. & Burtey, S. Emerging roles of aryl hydrocarbon receptors in the altered clearance of drugs during chronic kidney disease. Toxins 11, 209 (2019).","journal-title":"Toxins"},{"key":"408_CR187","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1681\/ASN.2017030361","volume":"29","author":"T Santana Machado","year":"2018","unstructured":"Santana Machado, T. et al. Indoxyl sulfate upregulates liver P-glycoprotein expression and activity through aryl hydrocarbon receptor signaling. J. Am. Soc. Nephrol. 29, 906\u2013918 (2018).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR188","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1080\/03602532.2016.1197240","volume":"48","author":"O Hankinson","year":"2016","unstructured":"Hankinson, O. The role of AHR-inducible cytochrome P450s in metabolism of polyunsaturated fatty acids. Drug Metab. Rev. 48, 342\u2013350 (2016).","journal-title":"Drug Metab. Rev."},{"issue":"Suppl. 13","key":"408_CR189","doi-asserted-by":"publisher","first-page":"4454","DOI":"10.1158\/1538-7445.AM2019-4454","volume":"79","author":"N Schmees","year":"2019","unstructured":"Schmees, N. et al. Identification of BAY-218, a potent and selective small-molecule AhR inhibitor, as a new modality to counteract tumor immunosuppression [abstract 4454]. Cancer Res. 79 (Suppl. 13), 4454 (2019).","journal-title":"Cancer Res."},{"key":"408_CR190","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1124\/mol.114.093369","volume":"86","author":"AJ Parks","year":"2014","unstructured":"Parks, A. J. et al. In silico identification of an aryl hydrocarbon receptor antagonist with biological activity in vitro and in vivo. Mol. Pharmacol. 86, 593\u2013608 (2014).","journal-title":"Mol. Pharmacol."},{"key":"408_CR191","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaw8412","volume":"11","author":"A Lin","year":"2019","unstructured":"Lin, A. et al. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Sci. Transl Med. 11, eaaw8412 (2019).","journal-title":"Sci. Transl Med."},{"key":"408_CR192","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1124\/jpet.110.178392","volume":"338","author":"KJ Smith","year":"2011","unstructured":"Smith, K. J. et al. Identification of a high-affinity ligand that exhibits complete aryl hydrocarbon receptor antagonism. J. Pharmacol. Exp. Ther. 338, 318\u2013327 (2011).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"408_CR193","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1124\/mol.109.061788","volume":"77","author":"IA Murray","year":"2010","unstructured":"Murray, I. A. et al. Evidence for ligand-mediated selective modulation of aryl hydrocarbon receptor activity. Mol. Pharmacol. 77, 247\u2013254 (2010).","journal-title":"Mol. Pharmacol."},{"key":"408_CR194","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1124\/mol.110.069369","volume":"79","author":"IA Murray","year":"2011","unstructured":"Murray, I. A. et al. Suppression of cytokine-mediated complement factor gene expression through selective activation of the Ah receptor with 3\u2032,4\u2032-dimethoxy-alpha-naphthoflavone. Mol. Pharmacol. 79, 508\u2013519 (2011).","journal-title":"Mol. Pharmacol."},{"key":"408_CR195","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1124\/jpet.109.158261","volume":"332","author":"IA Murray","year":"2010","unstructured":"Murray, I. A. et al. Antagonism of aryl hydrocarbon receptor signaling by 6,2\u2032,4\u2032-trimethoxyflavone. J. Pharmacol. Exp. Ther. 332, 135\u2013144 (2010).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"408_CR196","unstructured":"US National Library of Medicine. ClinicalTrials.gov https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04069026 (2021)."},{"key":"408_CR197","unstructured":"US National Library of Medicine. ClinicalTrials.gov https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04200963 (2020)."},{"key":"408_CR198","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1093\/aje\/kwv242","volume":"183","author":"H Zuo","year":"2016","unstructured":"Zuo, H. et al. Plasma biomarkers of inflammation, the kynurenine pathway, and risks of all-cause, cancer, and cardiovascular disease mortality: the hordaland health study. Am. J. Epidemiol. 183, 249\u2013258 (2016).","journal-title":"Am. J. Epidemiol."},{"key":"408_CR199","doi-asserted-by":"publisher","first-page":"6795","DOI":"10.1158\/0008-5472.CAN-17-2285","volume":"77","author":"GC Prendergast","year":"2017","unstructured":"Prendergast, G. C., Malachowski, W. P., DuHadaway, J. B. & Muller, A. J. Discovery of IDO1 inhibitors: from bench to bedside. Cancer Res. 77, 6795\u20136811 (2017).","journal-title":"Cancer Res."},{"key":"408_CR200","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1038\/nbt.4180","volume":"36","author":"TA Triplett","year":"2018","unstructured":"Triplett, T. A. et al. Reversal of indoleamine 2,3-dioxygenase-mediated cancer immune suppression by systemic kynurenine depletion with a therapeutic enzyme. Nat. Biotechnol. 36, 758\u2013764 (2018).","journal-title":"Nat. Biotechnol."},{"key":"408_CR201","doi-asserted-by":"publisher","first-page":"104024","DOI":"10.1155\/2013\/104024","volume":"2013","author":"R Lugo-Huitron","year":"2013","unstructured":"Lugo-Huitron, R. et al. Quinolinic acid: an endogenous neurotoxin with multiple targets. Oxid. Med. Cell. Longev. 2013, 104024 (2013).","journal-title":"Oxid. Med. Cell. Longev."},{"key":"408_CR202","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1681\/ASN.2012050536","volume":"24","author":"JM Bugnicourt","year":"2013","unstructured":"Bugnicourt, J. M., Godefroy, O., Chillon, J. M., Choukroun, G. & Massy, Z. A. Cognitive disorders and dementia in CKD: the neglected kidney-brain axis. J. Am. Soc. Nephrol. 24, 353\u2013363 (2013).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR203","doi-asserted-by":"publisher","first-page":"F721","DOI":"10.1152\/ajprenal.00141.2017","volume":"313","author":"J Wang","year":"2017","unstructured":"Wang, J. & Zhuang, S. Src family kinases in chronic kidney disease. Am. J. Physiol. Renal Physiol 313, F721\u2013F728 (2017).","journal-title":"Am. J. Physiol. Renal Physiol"},{"key":"408_CR204","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1093\/ndt\/gfu196","volume":"30","author":"A Lan","year":"2015","unstructured":"Lan, A. & Du, J. Potential role of Akt signaling in chronic kidney disease. Nephrol. Dial. Transpl. 30, 385\u2013394 (2015).","journal-title":"Nephrol. Dial. Transpl."},{"key":"408_CR205","doi-asserted-by":"publisher","first-page":"FSO204","DOI":"10.4155\/fsoa-2017-0010","volume":"3","author":"R Shahin","year":"2017","unstructured":"Shahin, R., Shaheen, O., El-Dahiyat, F., Habash, M. & Saffour, S. Research advances in kinase enzymes and inhibitors for cardiovascular disease treatment. Future Sci. OA 3, FSO204 (2017).","journal-title":"Future Sci. OA"},{"key":"408_CR206","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1159\/000326297","volume":"32","author":"JH Ryu","year":"2011","unstructured":"Ryu, J. H. & Kim, S. J. Clopidogrel effectively suppresses endothelial microparticle generation induced by indoxyl sulfate via inhibition of the p38 mitogen-activated protein kinase pathway. Blood Purif. 32, 186\u2013194 (2011).","journal-title":"Blood Purif."},{"key":"408_CR207","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1161\/CIRCRESAHA.110.233056","volume":"108","author":"AP Owens 3rd","year":"2011","unstructured":"Owens, A. P. 3rd. & Mackman, N. Microparticles in hemostasis and thrombosis. Circ. Res. 108, 1284\u20131297 (2011).","journal-title":"Circ. Res."},{"key":"408_CR208","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.tips.2015.04.005","volume":"36","author":"P Wu","year":"2015","unstructured":"Wu, P., Nielsen, T. E. & Clausen, M. H. FDA-approved small-molecule kinase inhibitors. Trends Pharmacol. Sci. 36, 422\u2013439 (2015).","journal-title":"Trends Pharmacol. Sci."},{"key":"408_CR209","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1038\/nm.3145","volume":"19","author":"RA Koeth","year":"2013","unstructured":"Koeth, R. A. et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 19, 576\u2013585 (2013).","journal-title":"Nat. Med."},{"key":"408_CR210","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1177\/1074248411419502","volume":"17","author":"J Kuka","year":"2012","unstructured":"Kuka, J. et al. The cardioprotective effect of mildronate is diminished after co-treatment with L-carnitine. J. Cardiovasc. Pharmacol. Ther. 17, 215\u2013222 (2012).","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"408_CR211","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.lfs.2014.09.028","volume":"117","author":"J Kuka","year":"2014","unstructured":"Kuka, J. et al. Suppression of intestinal microbiota-dependent production of pro-atherogenic trimethylamine N-oxide by shifting L-carnitine microbial degradation. Life Sci. 117, 84\u201392 (2014).","journal-title":"Life Sci."},{"key":"408_CR212","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1080\/1354750X.2018.1432689","volume":"23","author":"M Konop","year":"2018","unstructured":"Konop, M. et al. Enalapril decreases rat plasma concentration of TMAO, a gut bacteria-derived cardiovascular marker. Biomarkers 23, 380\u2013385 (2018).","journal-title":"Biomarkers"},{"key":"408_CR213","doi-asserted-by":"publisher","first-page":"19","DOI":"10.3390\/toxins10010019","volume":"10","author":"E Sato","year":"2017","unstructured":"Sato, E. et al. Impact of the oral adsorbent AST-120 on organ-specific accumulation of uremic toxins: LC-MS\/MS and MS imaging techniques. Toxins 10, 19 (2017).","journal-title":"Toxins"},{"key":"408_CR214","doi-asserted-by":"publisher","first-page":"367","DOI":"10.3390\/toxins10090367","volume":"10","author":"WC Liu","year":"2018","unstructured":"Liu, W. C., Tomino, Y. & Lu, K. C. Impacts of indoxyl sulfate and p-cresol sulfate on chronic kidney disease and mitigating effects of AST-120. Toxins 10, 367 (2018).","journal-title":"Toxins"},{"key":"408_CR215","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1080\/0886022X.2018.1561376","volume":"41","author":"M Asai","year":"2019","unstructured":"Asai, M., Kumakura, S. & Kikuchi, M. Review of the efficacy of AST-120 (KREMEZIN\u00ae) on renal function in chronic kidney disease patients. Ren. Fail. 41, 47\u201356 (2019).","journal-title":"Ren. Fail."},{"key":"408_CR216","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1159\/000453673","volume":"135","author":"J Yamaguchi","year":"2017","unstructured":"Yamaguchi, J., Tanaka, T. & Inagi, R. Effect of AST-120 in chronic kidney disease treatment: still a controversy? Nephron 135, 201\u2013206 (2017).","journal-title":"Nephron"},{"key":"408_CR217","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.1681\/ASN.2014010042","volume":"26","author":"G Schulman","year":"2015","unstructured":"Schulman, G. et al. Randomized placebo-controlled EPPIC trials of AST-120 in CKD. J. Am. Soc. Nephrol. 26, 1732\u20131746 (2015).","journal-title":"J. Am. Soc. Nephrol."},{"key":"408_CR218","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1007\/s10157-012-0717-0","volume":"17","author":"S Goto","year":"2013","unstructured":"Goto, S. et al. Association between AST-120 and abdominal aortic calcification in predialysis patients with chronic kidney disease. Clin. Exp. Nephrol. 17, 365\u2013371 (2013).","journal-title":"Clin. Exp. Nephrol."},{"key":"408_CR219","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1056\/NEJMoa021583","volume":"347","author":"G Eknoyan","year":"2002","unstructured":"Eknoyan, G. et al. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N. Engl. J. Med. 347, 2010\u20132019 (2002).","journal-title":"N. Engl. J. Med."},{"key":"408_CR220","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1038\/s41581-020-0287-4","volume":"16","author":"FP Wieringa","year":"2020","unstructured":"Wieringa, F. P. & Kooman, J. P. Smart sensors for real-time monitoring of patients on dialysis. Nat. Rev. Nephrol. 16, 554\u2013555 (2020).","journal-title":"Nat. Rev. Nephrol."}],"container-title":["Nature Reviews Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41581-021-00408-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41581-021-00408-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41581-021-00408-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,30]],"date-time":"2023-01-30T02:10:31Z","timestamp":1675044631000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41581-021-00408-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,23]]},"references-count":220,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["408"],"URL":"https:\/\/doi.org\/10.1038\/s41581-021-00408-4","relation":{},"ISSN":["1759-5061","1759-507X"],"issn-type":[{"value":"1759-5061","type":"print"},{"value":"1759-507X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,23]]},"assertion":[{"value":"4 February 2021","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 March 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}