{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T14:32:30Z","timestamp":1768833150198,"version":"3.49.0"},"reference-count":135,"publisher":"American Physiological Society","issue":"3","funder":[{"name":"no funding was received for the conception of this paper"}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2021,3,1]]},"abstract":"<jats:p> Patients treated with hemodialysis (HD) repeatedly undergo intradialytic low arterial oxygen saturation and low central venous oxygen saturation, reflecting an imbalance between upper body systemic oxygen supply and demand, which are associated with increased mortality. Abnormalities along the entire oxygen cascade, with impaired diffusive and convective oxygen transport, contribute to the reduced tissue oxygen supply. HD treatment impairs pulmonary gas exchange and reduces ventilatory drive, whereas ultrafiltration can reduce tissue perfusion due to a decline in cardiac output. In addition to these factors, capillary rarefaction and reduced mitochondrial efficacy can further affect the balance between cellular oxygen supply and demand. Whereas it has been convincingly demonstrated that a reduced perfusion of heart and brain during HD contributes to organ damage, the significance of systemic hypoxia remains uncertain, although it may contribute to oxidative stress, systemic inflammation, and accelerated senescence. These abnormalities along the oxygen cascade of patients treated with HD appear to be diametrically opposite to the situation in Tibetan highlanders and Sherpa, whose physiology adapted to the inescapable hypobaric hypoxia of their living environment over many generations. Their adaptation includes pulmonary, vascular, and metabolic alterations with enhanced capillary density, nitric oxide production, and mitochondrial efficacy without oxidative stress. Improving the tissue oxygen supply in patients treated with HD depends primarily on preventing hemodynamic instability by increasing dialysis time\/frequency or prescribing cool dialysis. Whether dietary or pharmacological interventions, such as the administration of L-arginine, fermented food, nitrate, nuclear factor erythroid 2-related factor 2 agonists, or prolyl hydroxylase 2 inhibitors, improve clinical outcome in patients treated with HD warrants future research. <\/jats:p>","DOI":"10.1152\/ajprenal.00540.2020","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T11:46:27Z","timestamp":1609155987000},"page":"F249-F261","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["The oxygen cascade in patients treated with hemodialysis and native high-altitude dwellers: lessons from extreme physiology to benefit patients with end-stage renal disease"],"prefix":"10.1152","volume":"320","author":[{"given":"Jeroen P.","family":"Kooman","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8785-4820","authenticated-orcid":false,"given":"Peter","family":"Stenvinkel","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine, Department of Clinical Science Technology and Intervention, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul G.","family":"Shiels","sequence":"additional","affiliation":[{"name":"Institute of Cancer Sciences, College of Medical, Veterinary and Life         Sciences, University of Glasgow, Glasgow, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Feelisch","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences and Integrative Physiology and Critical Illness Group, Faculty of Medicine, Southampton General Hospital and Institute for Life Sciences, University of Southampton, Southampton, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Canaud","sequence":"additional","affiliation":[{"name":"Montpellier University, School of         Medicine, Montpellier, France, and Global Medical Office,         Fresenius Medical Care, Bad Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Kotanko","sequence":"additional","affiliation":[{"name":"Renal Research Institute, New York, New York"},{"name":"Icahn School of Medicine at Mount Sinai, New York, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016060686"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/sdi.12704"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2017101088"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-09233-x"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1186\/cc10351"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.08510815"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00018.2014"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1042\/BST20170502"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1113\/EP086083"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1186\/cc5142"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/hdi.12129"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.133"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1007\/s10877-012-9350-4"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1186\/cc2353"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1159\/000441271"},{"key":"B16","first-page":"1","author":"Guven G","year":"2019","journal-title":"Blood Purif"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.4187\/respcare.03357"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfx309"},{"key":"B19","first-page":"297","volume":"18","author":"De Broe ME","year":"1989","journal-title":"Adv Nephrol Necker Hosp"},{"key":"B20","first-page":"820","volume":"38","author":"Ganss R","year":"1992","journal-title":"ASAIO J"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.chest.2019.09.004"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0195585"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.12659\/msm.896305"},{"key":"B24","first-page":"315","volume":"41","author":"Alfakir M","year":"2011","journal-title":"Ann Clin Lab Sci"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gft051"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.09.022"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010195"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1700527114"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2007111181"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.624544"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701985104"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002443107"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00605.2013"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006675"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2007.05.001"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1979.47.2.337"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.02160214"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1080\/00365519850186256"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1088\/1752-7155\/1\/2\/026005"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1088\/1752-7155\/2\/2\/026004"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1053\/j.jvca.2016.02.011"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1515\/CCLM.2003.137"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/396527"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1111\/sdi.12679"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-017-0483-z"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfx271"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12784"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfp267"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V961018"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0166050"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1053\/j.jrn.2017.04.012"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1960"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2015111219"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1113\/EP087236"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707462104"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/srep00109"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.221381098"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1113\/JP277590"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1126\/science.aab3896"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-3414fje"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1417566112"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-24024-8"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201901936RR"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00202.2019"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2016.05.011"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00442.2014"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.12780"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aeu404"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-38832-z"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1186\/cc9078"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00093.2016"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.169"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2017.01.051"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20123094"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.23876\/j.krcp.19.063"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.annemergmed.2009.08.014"},{"key":"B77","first-page":"93","volume":"50","author":"Barratt-Boyes BG","year":"1957","journal-title":"J Lab Clin Med"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1186\/cc5144"},{"key":"B79","first-page":"1049","volume":"79","author":"Ducrocq N","year":"2013","journal-title":"Minerva Anestesiol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1186\/cc1824"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-010-1980-8"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2369-15-4"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013101086"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0910283"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00391.2011"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.05.004"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA117.000470"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200800232"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2016.05.003"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12982"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-019-0233-3"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.4414\/smw.2017.14400"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2020.02.026"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101395"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-58906-7"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(99)06154-1"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.00125"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1097\/00002480-199207000-00039"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5000088"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V4121987"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1089\/ham.2017.0159"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.33594\/000000173"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2013.12.027"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7083"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2012.01.011"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2019.101113"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1016\/j.cophys.2019.04.009"},{"key":"B108","first-page":"1","author":"Sars B","year":"2019","journal-title":"Blood Purif"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.05200610"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V1181512"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31826a44f6"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfy376"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfx210"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1113\/EP087122"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2015.00058"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20153668"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneph0143"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1038\/s41514-017-0013-z"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2013.11.010"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900067R"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.07.027"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1007\/s40279-017-0744-9"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2019.10.004"},{"key":"B124","author":"Stenvinkel P","year":"2019","journal-title":"Nephrol Dial Transplant"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1042\/BST20190110"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.05.024"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13031"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1111\/joim.13021"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1007\/s12088-010-0058-1"},{"key":"B130","first-page":"285","volume":"89","author":"Jones RM","year":"2016","journal-title":"Yale J Biol Med"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-019-0235-1"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2018.00121"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11104"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2016.10.017"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2018.12.022"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00540.2020","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T17:33:55Z","timestamp":1629826435000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajprenal.00540.2020"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,1]]},"references-count":135,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3,1]]}},"alternative-id":["10.1152\/ajprenal.00540.2020"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00540.2020","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,1]]},"assertion":[{"value":"2020-10-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}