{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:27:23Z","timestamp":1787138843716,"version":"build-2736575974"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"crossref","award":["P01 HL147823"],"award-info":[{"award-number":["P01 HL147823"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"crossref","award":["R01HL103866"],"award-info":[{"award-number":["R01HL103866"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100017540","name":"NHLBI Division of Intramural Research","doi-asserted-by":"crossref","award":["R01HL167831"],"award-info":[{"award-number":["R01HL167831"]}],"id":[{"id":"10.13039\/100017540","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            Inhibition of the gut microbial trimethylamine\n                            <jats:italic toggle=\"yes\">N<\/jats:italic>\n                            -oxide (TMAO) pathway after CKD onset both halted disease progression and reversed pathophysiologic CKD features.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Inhibition of TMAO formation in established CKD animals improved kidney function, proteinuria, fibrosis, and uremic toxins.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In CKD models, a drug that suppressed gut microbial TMAO production yet remains in the intestinal lumen reversed kidney fibrosis and improved GFR.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Recent studies demonstrate gut microbial trimethylamine\n                      <jats:italic toggle=\"yes\">N<\/jats:italic>\n                      -oxide (TMAO) is clinically and mechanistically linked to CKD development. Prior studies showed selective targeting of gut microbial TMAO production can prevent CKD initiation. A highly relevant clinical question is whether inhibiting TMAO generation can reverse established kidney dysfunction and fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>CD1 mice were first randomized (phase 1) to unilateral nephrectomy (UNx) or sham surgery and fed a high-fat diet \u00b11% choline supplementation to document CKD through measures of multiple indices of kidney function, tissue remodeling\/fibrosis, and uremic toxins. Mice were then randomized (phase 2) to continue the same diet\u00b1fluoromethylcholine (FMC), a mechanism-based gut microbial TMAO inhibitor, for 8 additional weeks, and the impact on CKD-related phenotypes was assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After 12 weeks, choline-supplemented UNx mice exhibited 15-fold higher circulating TMAO levels. In parallel, multiple kidney dysfunction indices progressed, including 48% reduction in measured GFR (mGFR), elevated cystatin C and creatinine, 3.5-fold greater tubulointerstitial fibrosis, and upregulated profibrotic gene expression. After phase 2 (8 weeks\u00b1FMC), choline-supplemented (high-TMAO) UNx mice without FMC showed further elevation of circulating TMAO and multiple indices of progressive kidney function decline and fibrosis. Conversely, FMC-treated animals showed virtual elimination in circulating TMAO and significant improvements in all monitored CKD phenotypes, including &gt;50% higher mGFR, and improved (decreased) creatinine, cystatin C, pseudouridine, urinary albumin\/creatinine ratio, kidney fibrosis measures, and many uremic toxin levels (\n                      <jats:italic toggle=\"yes\">e.g<\/jats:italic>\n                      ., indoxyl sulfate and phenylacetylglycine). Beyond halting progression of kidney functional decline and fibrosis, there was frank regression in tubulointerstitial fibrosis (41% reduction) and significant improvement in mGFR (39% increase, end of phase 2 versus phase 1).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Pharmacologic targeting of gut microbial TMAO production after CKD establishment halted disease progression and promoted regression of key CKD pathophysiologic features.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.0000001171","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T22:00:34Z","timestamp":1783720834000},"update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Targeted Inhibition of Gut Microbial Trimethylamine N-Oxide Production Fosters Regression of CKD Phenotypes"],"prefix":"10.1681","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1641-1758","authenticated-orcid":false,"given":"Joseph A.","family":"DiDonato","sequence":"first","affiliation":[{"name":"Department of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, Ohio"},{"name":"Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor L.","family":"Weeks","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, Ohio"},{"name":"Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilaksh","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, Ohio"},{"name":"Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2703-4353","authenticated-orcid":false,"given":"Deepthi P.","family":"Mallela","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, Ohio"},{"name":"Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Buffa","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, Ohio"},{"name":"Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6455-8228","authenticated-orcid":false,"given":"Zeneng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, Ohio"},{"name":"Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4946-4271","authenticated-orcid":false,"given":"Xinmin S.","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, Ohio"},{"name":"Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2380-2527","authenticated-orcid":false,"given":"James T.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, Ohio"},{"name":"Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, Ohio"},{"name":"Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2407-769X","authenticated-orcid":false,"given":"Naseer","family":"Sangwan","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, Ohio"},{"name":"Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0657-7121","authenticated-orcid":false,"given":"Ina","family":"Nemet","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, Ohio"},{"name":"Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9616-1540","authenticated-orcid":false,"given":"Scott J.","family":"Cameron","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, Ohio"},{"name":"Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, Ohio"},{"name":"Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7124-6639","authenticated-orcid":false,"given":"Stanley L.","family":"Hazen","sequence":"additional","affiliation":[{"name":"Department of Heart, Blood, and Kidney Research, Cleveland Clinic, Cleveland, Ohio"},{"name":"Center for Microbiome and Human Health, Cleveland Clinic, Cleveland, Ohio"},{"name":"Department of Cardiovascular Medicine, Heart, Vascular, and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"issue":"1","key":"B2-20260819","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.kisu.2021.11.003","article-title":"Epidemiology of chronic kidney disease: an update 2022","volume":"12","author":"Kovesdy","year":"2022","journal-title":"Kidney Int Suppl (2011)."},{"issue":"3","key":"B3-20260819","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1161\/CIRCRESAHA.116.305360","article-title":"Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease","volume":"116","author":"Tang","year":"2015","journal-title":"Circ Res."},{"issue":"12","key":"B4-20260819","doi-asserted-by":"crossref","first-page":"2214","DOI":"10.1093\/ckj\/sfac154","article-title":"Decreasing microbiota-derived uremic toxins to improve CKD outcomes","volume":"15","author":"Beker","year":"2022","journal-title":"Clin Kidney J."},{"issue":"9","key":"B5-20260819","doi-asserted-by":"crossref","first-page":"626","DOI":"10.3390\/toxins14090626","article-title":"Gut-kidney axis investigations in animal models of chronic kidney disease","volume":"14","author":"Bartochowski","year":"2022","journal-title":"Toxins (Basel)."},{"issue":"2","key":"B6-20260819","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/ki.2012.345","article-title":"Chronic kidney disease alters intestinal microbial flora","volume":"83","author":"Vaziri","year":"2013","journal-title":"Kidney Int."},{"issue":"8","key":"B7-20260819","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1373\/clinchem.2005.050781","article-title":"Gas chromatographic-mass spectrometric analysis for measurement of p-cresol and its conjugated metabolites in uremic and normal serum","volume":"51","author":"de Loor","year":"2005","journal-title":"Clin Chem."},{"issue":"suppl 4","key":"B8-20260819","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1289\/ehp.97105s4739","article-title":"Genetic and environmental factors associated with variation of human xenobiotic glucuronidation and sulfation","volume":"105","author":"Burchell","year":"1997","journal-title":"Environ Health Perspect."},{"issue":"2","key":"B9-20260819","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/0009-8981(63)90165-7","article-title":"Urinary excretion of indoxyl sulphate (indican) and the interpretation of aromatic excretion patterns","volume":"8","author":"Curzon","year":"1963","journal-title":"Clin Chim Acta"},{"issue":"5","key":"B10-20260819","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1016\/j.cell.2020.02.016","article-title":"A cardiovascular disease-linked gut-microbial metabolite acts via adrenergic receptors","volume":"180","author":"Nemet","year":"2020","journal-title":"Cell."},{"issue":"7341","key":"B11-20260819","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nature09922","article-title":"Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease","volume":"472","author":"Wang","year":"2011","journal-title":"Nature."},{"issue":"3","key":"B12-20260819","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1373\/49.3.470","article-title":"Toxicity of free p-cresol: a prospective and cross-sectional analysis","volume":"49","author":"De Smet","year":"2003","journal-title":"Clin Chem."},{"issue":"8","key":"B13-20260819","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1681\/ASN.V1081815","article-title":"Pathophysiologic effects of uremic retention solutes","volume":"10","author":"Vanholder","year":"1999","journal-title":"J Am Soc Nephrol."},{"issue":"6","key":"B14-20260819","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1681\/ASN.0000000000000344","article-title":"The gut-microbial metabolite trimethylamine N-oxide, incident CKD, and kidney function decline","volume":"35","author":"Wang","year":"2024","journal-title":"J Am Soc Nephrol."},{"issue":"11","key":"B15-20260819","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.2215\/CJN.0000000812","article-title":"Associations of plasma trimethylamine N-oxide-related metabolites with the development and progression of albuminuria: the multiethnic study of atherosclerosis","volume":"20","author":"Wang","year":"2025","journal-title":"Clin J Am Soc Nephrol."},{"issue":"1","key":"B16-20260819","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/s41598-020-80063-0","article-title":"Inhibition of microbiota-dependent TMAO production attenuates chronic kidney disease in mice","volume":"11","author":"Zhang","year":"2021","journal-title":"Sci Rep."},{"issue":"5","key":"B17-20260819","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1161\/ATVBAHA.120.314139","article-title":"Targeted inhibition of gut-microbial trimethylamine N-oxide production reduces renal tubulointerstitial fibrosis and functional impairment in a murine model of chronic kidney disease","volume":"40","author":"Gupta","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol."},{"issue":"5","key":"B18-20260819","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1007\/s10157-015-1207-y","article-title":"Associations among serum trimethylamine-N-oxide (TMAO) levels, kidney function and infarcted coronary artery number in patients undergoing cardiovascular surgery: a cross-sectional study","volume":"20","author":"Mafune","year":"2016","journal-title":"Clin Exp Nephrol."},{"issue":"5","key":"B19-20260819","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1016\/j.kint.2016.01.014","article-title":"Advanced chronic kidney disease populations have elevated trimethylamine N-oxide levels associated with increased cardiovascular events","volume":"89","author":"Kim","year":"2016","journal-title":"Kidney Int."},{"issue":"1","key":"B20-20260819","doi-asserted-by":"crossref","first-page":"e0141738","DOI":"10.1371\/journal.pone.0141738","article-title":"Serum trimethylamine-N-oxide is strongly related to renal function and predicts outcome in chronic kidney disease","volume":"11","author":"Missailidis","year":"2016","journal-title":"PLoS One."},{"issue":"1","key":"B21-20260819","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1681\/ASN.2014111063","article-title":"Serum trimethylamine-N-oxide is elevated in CKD and correlates with coronary atherosclerosis burden","volume":"27","author":"Stubbs","year":"2016","journal-title":"J Am Soc Nephrol."},{"issue":"7","key":"B22-20260819","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1016\/j.cell.2015.11.055","article-title":"Non-lethal inhibition of gut-microbial trimethylamine production for the treatment of atherosclerosis","volume":"163","author":"Wang","year":"2015","journal-title":"Cell."},{"issue":"9","key":"B23-20260819","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1038\/s41591-018-0128-1","article-title":"Development of a gut microbe-targeted nonlethal therapeutic to inhibit thrombosis potential","volume":"24","author":"Roberts","year":"2018","journal-title":"Nat Med."},{"issue":"10","key":"B24-20260819","doi-asserted-by":"crossref","first-page":"e016223","DOI":"10.1161\/JAHA.119.016223","article-title":"Nonlethal inhibition of gut-microbial trimethylamine N-oxide production improves cardiac function and remodeling in a murine model of heart failure","volume":"9","author":"Organ","year":"2020","journal-title":"J Am Heart Assoc."},{"issue":"14","key":"B25-20260819","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1161\/CIRCULATIONAHA.122.060573","article-title":"Gut microbiota-derived trimethylamine N-oxide contributes to abdominal aortic aneurysm through inflammatory and apoptotic mechanisms","volume":"147","author":"Benson","year":"2023","journal-title":"Circulation."},{"issue":"2 Pt 2","key":"B26-20260819","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1161\/hy0202.103297","article-title":"Role of methoxyestradiols in the growth inhibitory effects of estradiol on human glomerular mesangial cells","volume":"39","author":"Dubey","year":"2002","journal-title":"Hypertension."},{"issue":"46","key":"B27-20260819","doi-asserted-by":"crossref","first-page":"42908","DOI":"10.1074\/jbc.M105316200","article-title":"Cross-talk between transforming growth factor-beta and estrogen receptor signaling through Smad3","volume":"276","author":"Matsuda","year":"2001","journal-title":"J Biol Chem."},{"issue":"2","key":"B28-20260819","doi-asserted-by":"crossref","first-page":"F399","DOI":"10.1152\/ajprenal.00195.2004","article-title":"17beta-estradiol replacement improves renal function and pathology associated with diabetic nephropathy","volume":"288","author":"Mankhey","year":"2005","journal-title":"Am J Physiol Renal Physiol."},{"issue":"6","key":"B29-20260819","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1038\/ki.2013.45","article-title":"Albuminuria is associated with too few glomeruli and too much testosterone","volume":"83","author":"Long","year":"2013","journal-title":"Kidney Int."},{"issue":"140","key":"B30-20260819","first-page":"58520","article-title":"Transdermal measurement of glomerular filtration rate in mice","author":"Scarfe","year":"2018","journal-title":"J Vis Exp"},{"issue":"7","key":"B31-20260819","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1093\/eurheartj\/ehy799","article-title":"Impact of chronic dietary red meat, white meat, or non-meat protein on trimethylamine N-oxide metabolism and renal excretion in healthy men and women","volume":"40","author":"Wang","year":"2019","journal-title":"Eur Heart J."},{"issue":"32","key":"B32-20260819","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.1093\/eurheartj\/ehad333","article-title":"Atlas of gut microbe-derived products from aromatic amino acids and risk of cardiovascular morbidity and mortality","volume":"44","author":"Nemet","year":"2023","journal-title":"Eur Heart J."},{"issue":"7","key":"B33-20260819","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1038\/nmeth.3869","article-title":"DADA2: high-resolution sample inference from illumina amplicon data","volume":"13","author":"Callahan","year":"2016","journal-title":"Nat Methods."},{"issue":"3","key":"B34-20260819","doi-asserted-by":"crossref","first-page":"421","DOI":"10.11594\/jtls.13.03.01","article-title":"In-silico molecular phylogeny of Philippine myxomycetes using 18S rRNA and small subunit rRNA (SSU) gene sequences","volume":"13","author":"Ong","year":"2023","journal-title":"J Trop Life Sci."},{"issue":"4","key":"B35-20260819","doi-asserted-by":"crossref","first-page":"e61217","DOI":"10.1371\/journal.pone.0061217","article-title":"Phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data","volume":"8","author":"McMurdie","year":"2013","journal-title":"PLoS One."},{"issue":"24","key":"B36-20260819","doi-asserted-by":"crossref","first-page":"13477","DOI":"10.3390\/ijms222413477","article-title":"The nutritional supplement L-alpha glycerylphosphorylcholine promotes atherosclerosis","volume":"22","author":"Wang","year":"2021","journal-title":"Int J Mol Sci."},{"issue":"6","key":"B37-20260819","doi-asserted-by":"crossref","first-page":"295","DOI":"10.3390\/toxins17060295","article-title":"From physicochemical classification to multidimensional insights: a comprehensive review of uremic toxin research","volume":"17","author":"Cozzolino","year":"2025","journal-title":"Toxins (Basel)."},{"issue":"2","key":"B38-20260819","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/sj.ki.5000054","article-title":"Renal fibrosis: new insights into the pathogenesis and therapeutics","volume":"69","author":"Liu","year":"2006","journal-title":"Kidney Int."},{"issue":"1","key":"B39-20260819","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/s41392-023-01379-7","article-title":"Kidney fibrosis: from mechanisms to therapeutic medicines","volume":"8","author":"Huang","year":"2023","journal-title":"Signal Transduct Target Ther."},{"issue":"1","key":"B40-20260819","doi-asserted-by":"crossref","first-page":"408","DOI":"10.3390\/ijms22010408","article-title":"Fibrosis in chronic kidney disease: pathogenesis and consequences","volume":"22","author":"Panizo","year":"2021","journal-title":"Int J Mol Sci."},{"issue":"4","key":"B41-20260819","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.kint.2023.10.016","article-title":"Executive summary of the KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease: known knowns and known unknowns","volume":"105","author":"Levin","year":"2024","journal-title":"Kidney Int."},{"issue":"4","key":"B42-20260819","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1681\/ASN.V24832","article-title":"Is there a \u201cpoint of no return\u201d in progressive renal disease?","volume":"2","author":"Maschio","year":"1991","journal-title":"J Am Soc Nephrol."},{"issue":"9","key":"B43-20260819","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1681\/ASN.2010121220","article-title":"Colonic contribution to uremic solutes","volume":"22","author":"Aronov","year":"2011","journal-title":"J Am Soc Nephrol."},{"issue":"6","key":"B44-20260819","doi-asserted-by":"crossref","first-page":"1986","DOI":"10.3390\/ijms21061986","article-title":"Isolation and quantification of uremic toxin precursor-generating gut bacteria in chronic kidney disease patients","volume":"21","author":"Gryp","year":"2020","journal-title":"Int J Mol Sci."},{"issue":"3","key":"B45-20260819","doi-asserted-by":"crossref","first-page":"101484","DOI":"10.1016\/j.beem.2021.101484","article-title":"Intestinal microbiota and diabetic kidney diseases: the role of microbiota and derived metabolites inmodulation of renal inflammation and disease progression","volume":"35","author":"Mosterd","year":"2021","journal-title":"Best Pract Res Clin Endocrinol Metab."},{"key":"B46-20260819","doi-asserted-by":"crossref","first-page":"156195","DOI":"10.1016\/j.phymed.2024.156195","article-title":"Suyin detoxification granule alleviates trimethylamine N-oxide-induced tubular ferroptosis and renal fibrosis to prevent chronic kidney disease progression","volume":"135","author":"Ge","year":"2024","journal-title":"Phytomedicine."},{"issue":"6","key":"B47-20260819","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1016\/j.kint.2024.01.040","article-title":"Antibiotic-induced intestinal microbiota depletion can attenuate the acute kidney injury to chronic kidney disease transition via NADPH oxidase 2 and trimethylamine-N-oxide inhibition","volume":"105","author":"Lee","year":"2024","journal-title":"Kidney Int."},{"issue":"1","key":"B48-20260819","doi-asserted-by":"crossref","first-page":"5843","DOI":"10.1038\/s41467-023-39824-4","article-title":"Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide","volume":"14","author":"Andrikopoulos","year":"2023","journal-title":"Nat Commun."},{"issue":"11","key":"B49-20260819","doi-asserted-by":"crossref","first-page":"2877","DOI":"10.1681\/ASN.2021030336","article-title":"Impaired tubular secretion of organic solutes in advanced chronic kidney disease","volume":"32","author":"Mair","year":"2021","journal-title":"J Am Soc Nephrol."},{"issue":"36","key":"B50-20260819","doi-asserted-by":"crossref","first-page":"13546","DOI":"10.1021\/acs.analchem.3c02069","article-title":"Multitargeted internal calibration for the quantification of chronic kidney disease-related endogenous metabolites using liquid chromatography-mass spectrometry","volume":"95","author":"Visconti","year":"2023","journal-title":"Anal Chem."},{"issue":"17","key":"B51-20260819","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1056\/NEJMoa1109400","article-title":"Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk","volume":"368","author":"Tang","year":"2013","journal-title":"N Engl J Med."},{"issue":"11","key":"B52-20260819","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1136\/gutjnl-2015-309957","article-title":"High-level adherence to a mediterranean diet beneficially impacts the gut microbiota and associated metabolome","volume":"65","author":"De Filippis","year":"2016","journal-title":"Gut."},{"issue":"5","key":"B53-20260819","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1093\/advances\/nmz012","article-title":"Modulation of circulating trimethylamine N-oxide concentrations by dietary supplements and pharmacological agents: a systematic review","volume":"10","author":"Kalagi","year":"2019","journal-title":"Adv Nutr."},{"issue":"5","key":"B54-20260819","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1093\/ajcn\/nqaa203","article-title":"A randomized crossover trial on the effect of plant-based compared with animal-based meat on trimethylamine-N-oxide and cardiovascular disease risk factors in generally healthy adults: study with appetizing plantfood-meat eating alternative trial (SWAP-MEAT)","volume":"112","author":"Crimarco","year":"2020","journal-title":"Am J Clin Nutr."},{"issue":"7","key":"B55-20260819","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1093\/jn\/nxab046","article-title":"Evaluation of an 8-week vegan diet on plasma trimethylamine-N-oxide and postchallenge glucose in adults with dysglycemia or obesity","volume":"151","author":"Argyridou","year":"2021","journal-title":"J Nutr."},{"issue":"5","key":"B56-20260819","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.3390\/nu14051093","article-title":"Fasting-mimicking diet reduces trimethylamine N-oxide levels and improves serum biochemical parameters in healthy volunteers","volume":"14","author":"Videja","year":"2022","journal-title":"Nutrients."},{"issue":"19","key":"B57-20260819","doi-asserted-by":"crossref","first-page":"3135","DOI":"10.3390\/nu17193135","article-title":"Short-term mediterranean dietary intervention reduces plasma trimethylamine-N-oxide levels in healthy individuals","volume":"17","author":"Deniz","year":"2025","journal-title":"Nutrients."},{"issue":"5","key":"B58-20260819","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.amjcard.2022.05.010","article-title":"Relation of statin use to gut-microbial trimethylamine N-oxide and cardiovascular risk","volume":"178","author":"Li","year":"2022","journal-title":"Am J Cardiol"},{"issue":"1","key":"B59-20260819","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s12944-022-01673-3","article-title":"The associations between TMAO-related metabolites and blood lipids and the potential impact of rosuvastatin therapy","volume":"21","author":"Xiong","year":"2022","journal-title":"Lipids Health Dis."},{"issue":"17","key":"B60-20260819","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1161\/CIRCULATIONAHA.116.025338","article-title":"Gut microbe-generated trimethylamine N-oxide from dietary choline is prothrombotic in subjects","volume":"135","author":"Zhu","year":"2017","journal-title":"Circulation."},{"issue":"6","key":"B61-20260819","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1016\/j.cmet.2017.04.033","article-title":"A guide for the design of pre-clinical studies on sex differences in metabolism","volume":"25","author":"Mauvais-Jarvis","year":"2017","journal-title":"Cell Metab."},{"issue":"1","key":"B62-20260819","doi-asserted-by":"crossref","first-page":"16635","DOI":"10.1038\/s41598-023-42670-5","article-title":"Both sexes develop DKD in the CD1 uninephrectomized streptozotocin mouse model","volume":"13","author":"Trink","year":"2023","journal-title":"Sci Rep."},{"issue":"1","key":"B63-20260819","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.kint.2024.08.038","article-title":"Sex dimorphism in kidney health and disease: mechanistic insights and clinical implication","volume":"107","author":"Steiger","year":"2025","journal-title":"Kidney Int."},{"key":"B64-20260819","doi-asserted-by":"crossref","first-page":"e63998","DOI":"10.7554\/eLife.63998","article-title":"Gut microbe-targeted choline trimethylamine lyase inhibition improves obesity via rewiring of host circadian rhythms","volume":"11","author":"Schugar","year":"2022","journal-title":"eLife."}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001171","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:00:42Z","timestamp":1787137242000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.0000001171"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":63,"URL":"https:\/\/doi.org\/10.1681\/asn.0000001171","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,10]]},"assertion":[{"value":"2025-12-18","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-07","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}