{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:30:30Z","timestamp":1786480230488,"version":"build-2736575974"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01 DK101674"],"award-info":[{"award-number":["R01 DK101674"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01 NS054791"],"award-info":[{"award-number":["R01 NS054791"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 DK118426"],"award-info":[{"award-number":["R01 DK118426"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01 DK101674"],"award-info":[{"award-number":["R01 DK101674"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["R01 NS054791"],"award-info":[{"award-number":["R01 NS054791"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 DK118426"],"award-info":[{"award-number":["R01 DK118426"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2025,5]]},"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>Hemodialysis can relieve uremic symptoms only by lowering the plasma levels of causative solutes below what they were at dialysis initiation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>This can happen only when the ratio of a solute's dialytic clearance to the clearance of the failing kidney is very high.<\/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>If GFR falls far enough, uremic symptoms, such as anorexia and nausea, prompt the initiation of dialysis. Thrice-weekly hemodialysis can prevent recurrence of these symptoms even when patients become anuric. To accomplish this, it must maintain the plasma levels of the uremic solutes, which cause these symptoms to be lower than they were when dialysis was initiated. This study examined kinetic properties that solutes must possess for hemodialysis to accomplish this. We also sought to identify uremic solutes that possess these properties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mathematical modeling analyzed how a solute's kinetic properties would determine the relation of its level in an anuric patient on dialysis to its level when uremic symptoms prompt dialysis initiation. The previously unstudied solute methylurea (MU) was assayed by liquid chromatography tandem mass spectrometry in 13 participants on hemodialysis, nine participants with advanced CKD, and ten participants without kidney disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mathematical modeling showed that conventional dialysis can effectively control the plasma levels better than the failing native kidneys only of solutes, which have a high dialytic clearance relative to their native kidney clearance and a large volume of distribution. Liquid chromatography tandem mass spectrometry measurements showed that MU has these properties. The dialytic clearance of MU was 255\u00b132 ml\/min, and its volume of distribution was 1.09\u00b10.25 times the body water volume in patients on hemodialysis. The MU clearance was lower than the GFR in patients without kidney disease (fractional clearance 0.44\u00b10.19) and patients with advanced CKD (fractional clearance 0.53\u00b10.10). A literature review revealed that urea was the only solute previously known to possess these properties.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A further search for solutes whose properties include a high dialytic clearance, a relatively low native kidney clearance, and a high volume of distribution could help identify solutes that contribute to uremic symptoms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.34067\/kid.0000000712","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T12:02:28Z","timestamp":1737979348000},"page":"814-823","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Properties of Uremic Solutes That Allow Their Effective Control by Hemodialysis"],"prefix":"10.34067","volume":"6","author":[{"given":"Tanuja","family":"Yalamarti","sequence":"first","affiliation":[{"name":"Departments of Medicine, Stanford University and VA Palo Alto HCS, Palo Alto, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy L.","family":"Sirich","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Stanford University and VA Palo Alto HCS, Palo Alto, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0360-8973","authenticated-orcid":false,"given":"Xin","family":"Hai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Harbin Medical University, Harbin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6754-1299","authenticated-orcid":false,"given":"Josef K.","family":"Suba","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Stanford University and VA Palo Alto HCS, Palo Alto, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7742-4913","authenticated-orcid":false,"given":"Lindsey S.","family":"Keo","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Stanford University and VA Palo Alto HCS, Palo Alto, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5347-3501","authenticated-orcid":false,"given":"Kristy H.C.","family":"Chan","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Stanford University and VA Palo Alto HCS, Palo Alto, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9707-5399","authenticated-orcid":false,"given":"Timothy W.","family":"Meyer","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Stanford University and VA Palo Alto HCS, Palo Alto, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"issue":"2","key":"B1-20250530","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.semnephrol.2014.02.001","article-title":"Introduction: uremic toxicity - state of the art 2014","volume":"34","author":"Vanholder","year":"2014","journal-title":"Semin Nephrol."},{"issue":"7","key":"B2-20250530","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1097\/MAT.0000000000001074","article-title":"Quantifying the effect of plasma viscosity on in vivo dialyzer performance","volume":"66","author":"Schneditz","year":"2020","journal-title":"ASAIO J."},{"issue":"7","key":"B3-20250530","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1016\/j.bbamem.2007.04.010","article-title":"Comparative transport efficiencies of urea analogues through urea transporter UT-B","volume":"1768","author":"Zhao","year":"2007","journal-title":"Biochim Biophys Acta."},{"key":"B4-20250530","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1152\/ajplegacy.1965.209.1.188","article-title":"Mechanism of renal excretion of methylurea and acetamide in the dog","volume":"209","author":"Rabinowitz","year":"1965","journal-title":"Am J Physiol."},{"issue":"11","key":"B5-20250530","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":"9","key":"B6-20250530","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.2215\/CJN.03150318","article-title":"Characteristics of colon-derived uremic solutes","volume":"13","author":"Mair","year":"2018","journal-title":"Clin J Am Soc Nephrol."},{"issue":"17","key":"B7-20250530","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1056\/NEJM198710223171717","article-title":"Simplified calculation of body-surface area","volume":"317","author":"Mosteller","year":"1987","journal-title":"N Engl J Med."},{"issue":"1","key":"B8-20250530","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/ajcn\/33.1.27","article-title":"Total body water volumes for adult males and females estimated from simple anthropometric measurements","volume":"33","author":"Watson","year":"1980","journal-title":"Am J Clin Nutr."},{"issue":"5","key":"B9-20250530","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1053\/j.ajkd.2009.06.033","article-title":"Solute-solver: a web-based tool for modeling urea kinetics for a broad range of hemodialysis schedules in multiple patients","volume":"54","author":"Daugirdas","year":"2009","journal-title":"Am J Kidney Dis."},{"issue":"3","key":"B10-20250530","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1681\/ASN.2013060597","article-title":"Prominent accumulation in hemodialysis patients of solutes normally cleared by tubular secretion","volume":"25","author":"Sirich","year":"2014","journal-title":"J Am Soc Nephrol."},{"issue":"11","key":"B11-20250530","doi-asserted-by":"crossref","first-page":"e0242254","DOI":"10.1371\/journal.pone.0242254","article-title":"Rate of decline in residual kidney function pre and post peritoneal dialysis initiation: a post hoc analysis of the IDEAL study","volume":"15","author":"Ethier","year":"2020","journal-title":"PLoS One."},{"issue":"3","key":"B12-20250530","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.kint.2021.07.025","article-title":"A multicenter feasibility randomized controlled trial to assess the impact of incremental versus conventional initiation of hemodialysis on residual kidney function","volume":"101","author":"Vilar","year":"2022","journal-title":"Kidney Int."},{"issue":"7","key":"B13-20250530","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1681\/ASN.2011121175","article-title":"Normal and pathologic concentrations of uremic toxins","volume":"23","author":"Duranton","year":"2012","journal-title":"J Am Soc Nephrol."},{"issue":"6","key":"B14-20250530","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1681\/ASN.2009111132","article-title":"Gerszten RE: metabolite profiling identifies markers of uremia","volume":"21","author":"Rhee","year":"2010","journal-title":"J Am Soc Nephrol."},{"issue":"2","key":"B15-20250530","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.kint.2021.10.035","article-title":"A metabolomics approach identified toxins associated with uremic symptoms in advanced chronic kidney disease","volume":"101","author":"Hu","year":"2022","journal-title":"Kidney Int."},{"issue":"1","key":"B16-20250530","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1056\/NEJM195201032460105","article-title":"The artificial kidney","volume":"246","author":"Merrill","year":"1952","journal-title":"N Engl J Med."},{"key":"B17-20250530","first-page":"114","article-title":"The treatment of chronic uremia by means of intermittent hemodialysis: a preliminary report","volume":"6","author":"Scribner","year":"1960","journal-title":"Trans Am Soc Artif Intern Organs."},{"key":"B18-20250530","first-page":"81","article-title":"The genesis of the square meter-hour hypothesis","volume":"17","author":"Babb","year":"1971","journal-title":"Trans Am Soc Artif Intern Organs."},{"issue":"3","key":"B19-20250530","first-page":"42","article-title":"The artificial kidney","volume":"8","author":"Schreiner","year":"1959","journal-title":"Heart Bull."},{"issue":"1","key":"B20-20250530","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/j.1525-1594.1978.tb01002.x","article-title":"Uremic neuropathy: evidence of middle molecule toxicity","volume":"2","author":"Milutinovic","year":"1978","journal-title":"Artif Organs."},{"key":"B21-20250530","first-page":"107","article-title":"Uremic blood cleansing by diafiltration using a hollow fiber ultrafilter","volume":"16","author":"Henderson","year":"1970","journal-title":"Trans Am Soc Artif Intern Organs."},{"issue":"5","key":"B22-20250530","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1097\/01.MAT.0000085985.34472.91","article-title":"The beginning of clinical hemofiltration: a personal account","volume":"49","author":"Henderson","year":"2003","journal-title":"ASAIO J."},{"issue":"suppl 3","key":"B23-20250530","doi-asserted-by":"crossref","first-page":"iii22","DOI":"10.1093\/ndt\/gfy228","article-title":"Membrane innovation: closer to native kidneys","volume":"33","author":"Storr","year":"2018","journal-title":"Nephrol Dial Transplant."},{"issue":"suppl 3","key":"B24-20250530","doi-asserted-by":"crossref","first-page":"iii53","DOI":"10.1093\/ndt\/gfy218","article-title":"Clinical evidence on haemodiafiltration","volume":"33","author":"Blankestijn","year":"2018","journal-title":"Nephrol Dial Transplant."},{"issue":"1","key":"B25-20250530","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1053\/j.jrn.2011.10.026","article-title":"An update on protein-bound uremic retention solutes","volume":"22","author":"Vanholder","year":"2012","journal-title":"J Ren Nutr."},{"issue":"6","key":"B26-20250530","doi-asserted-by":"crossref","first-page":"402","DOI":"10.3390\/toxins14060402","article-title":"The dual roles of protein-bound solutes as toxins and signaling molecules in uremia","volume":"14","author":"Masereeuw","year":"2022","journal-title":"Toxins (Basel)."},{"issue":"suppl 1","key":"B27-20250530","first-page":"1","article-title":"Improving solute clearances by hemodialysis","volume":"51","author":"Lee","year":"2022","journal-title":"Blood Purif."},{"issue":"2","key":"B28-20250530","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1053\/j.ajkd.2007.05.009","article-title":"Complex compartmental behavior of small water-soluble uremic retention solutes: evaluation by direct measurements in plasma and erythrocytes","volume":"50","author":"Eloot","year":"2007","journal-title":"Am J Kidney Dis."},{"issue":"4","key":"B29-20250530","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1111\/j.1523-1755.2005.00238.x","article-title":"Kinetic behavior of urea is different from that of other water-soluble compounds: the case of the guanidino compounds","volume":"67","author":"Eloot","year":"2005","journal-title":"Kidney Int."},{"issue":"2","key":"B30-20250530","doi-asserted-by":"crossref","first-page":"e0246765","DOI":"10.1371\/journal.pone.0246765","article-title":"Metabolomic analysis of uremic pruritus in patients on hemodialysis","volume":"16","author":"Bolanos","year":"2021","journal-title":"PLoS One."},{"issue":"5","key":"B31-20250530","first-page":"341","article-title":"Factors affecting the metabolic production of methylguanidine","volume":"48","author":"Gonella","year":"1975","journal-title":"Clin Sci Mol Med."},{"issue":"3","key":"B32-20250530","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1159\/000186149","article-title":"Production of methylguanidine from creatinine in normal rats and rats with renal failure","volume":"56","author":"Yokozawa","year":"1990","journal-title":"Nephron."},{"issue":"1","key":"B33-20250530","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1159\/000186376","article-title":"Production of methylguanidine from creatinine via creatol by active oxygen species: analyses of the catabolism in vitro","volume":"58","author":"Nakamura","year":"1991","journal-title":"Nephron."},{"issue":"3","key":"B34-20250530","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1038\/s41589-022-01154-9","article-title":"Hepatic glutamine synthetase controls N(5)-methylglutamine in homeostasis and cancer","volume":"19","author":"Villar","year":"2023","journal-title":"Nat Chem Biol."},{"issue":"8","key":"B35-20250530","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1139\/o83-108","article-title":"Metabolism of NG-monomethyl-L-arginine","volume":"61","author":"Paik","year":"1983","journal-title":"Can J Biochem Cell Biol."},{"issue":"3","key":"B36-20250530","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1053\/j.ajkd.2016.02.037","article-title":"Patient and caregiver priorities for outcomes in hemodialysis: an international nominal group technique study","volume":"68","author":"Urquhart-Secord","year":"2016","journal-title":"Am J Kidney Dis."},{"issue":"11","key":"B37-20250530","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.2215\/CJN.05880420","article-title":"Validation of a core patient-reported outcome measure for fatigue in patients receiving hemodialysis: the SONG-HD fatigue instrument","volume":"15","author":"Ju","year":"2020","journal-title":"Clin J Am Soc Nephrol."},{"issue":"2","key":"B38-20250530","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1111\/sdi.13080","article-title":"\u201cWhat matters to you?\u201d: the relevance of patient priorities in dialysis care for assessment and clinical practice","volume":"36","author":"Tommel","year":"2023","journal-title":"Semin Dial."},{"issue":"9","key":"B39-20250530","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1681\/ASN.2013101062","article-title":"The uremic toxicity of indoxyl sulfate and p-cresyl sulfate: a systematic review","volume":"25","author":"Vanholder","year":"2014","journal-title":"J Am Soc Nephrol."},{"issue":"5","key":"B40-20250530","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":"11","key":"B41-20250530","doi-asserted-by":"crossref","first-page":"3479","DOI":"10.1681\/ASN.2015121302","article-title":"Microbiota-derived phenylacetylglutamine associates with overall mortality and cardiovascular disease in patients with CKD","volume":"27","author":"Poesen","year":"2016","journal-title":"J Am Soc Nephrol."}],"container-title":["Kidney360"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0000000712","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T19:59:13Z","timestamp":1786478353000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0000000712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,27]]},"references-count":41,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025]]}},"URL":"https:\/\/doi.org\/10.34067\/kid.0000000712","relation":{},"ISSN":["2641-7650"],"issn-type":[{"value":"2641-7650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,27]]},"assertion":[{"value":"2024-10-16","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-16","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}