{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T13:21:35Z","timestamp":1762867295077,"version":"3.41.2"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,12,14]],"date-time":"2017-12-14T00:00:00Z","timestamp":1513209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008578","name":"Jubil\u00e4umsstiftung der Schweizerischen Lebensversicherungs- und Rentenanstalt f\u00fcr Volksgesundheit und medizinische Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008578","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic kidney disease (<jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>) exacerbates the risk of death due to cardiovascular disease (<jats:styled-content style=\"fixed-case\">CVD<\/jats:styled-content>). Modifications to blood lipid metabolism which manifest as increases in circulating triglycerides and reductions in high\u2010density lipoprotein (<jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>) cholesterol are thought to contribute to increased risk. In <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content> patients, higher <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content> cholesterol levels were not associated with reduced mortality risk. Recent research has revealed numerous mechanisms by which <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content> could favourably influence <jats:styled-content style=\"fixed-case\">CVD<\/jats:styled-content> risk. In this study, we compared plasma levels of sphingosine\u20101\u2010phosphate (S1P), <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>\u2010associated S1P (<jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>\u2010S1P) and <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>\u2010mediated protection against oxidative stress between <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content> and control patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>High\u2010density lipoprotein was individually isolated from 20 <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content> patients and 20 controls. Plasma S1P, apolipoprotein M (apoM) concentrations, <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>\u2010S1P content and the capacity of <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content> to protect cardiomyocytes against doxorubicin\u2010induced oxidative stress in\u00a0vitro were measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Chronic kidney disease patients showed a typical profile with significant reductions in plasma <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content> cholesterol and albumin and an increase in triglycerides and pro\u2010inflammatory cytokines (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010alpha and <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20106). Unexpectedly, <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>\u2010S1P content (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.001) and <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content> cardioprotective capacity (<jats:italic>P<\/jats:italic>\u00a0=\u00a0.034) were increased significantly in <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content> patients. Linear regression analysis of which factors could influence <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>\u2010S1P content showed an independent, negative and positive association with plasma albumin and apoM levels, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The novel and unexpected observation in this study is that uremic <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content> is more effective than control <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content> for protecting cardiomyocytes against oxidative stress. It is explained by its higher S1P content which we previously demonstrated to be the determinant of <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>\u2010mediated cardioprotective capacity. Interestingly, lower concentrations of albumin in <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content> are associated with higher <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>\u2010S1P.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.12866","type":"journal-article","created":{"date-parts":[[2017,11,27]],"date-time":"2017-11-27T11:43:00Z","timestamp":1511782980000},"source":"Crossref","is-referenced-by-count":19,"title":["High\u2010density lipoprotein from end\u2010stage renal disease patients exhibits superior cardioprotection and increase in sphingosine\u20101\u2010phosphate"],"prefix":"10.1111","volume":"48","author":[{"given":"Jonas W.","family":"Brinck","sequence":"first","affiliation":[{"name":"Division of Endocrinology Diabetology, Hypertension and Nutrition Department of Internal Medicine Specialities Medical Faculty Geneva University Geneva Switzerland"},{"name":"Metabolism Unit Department of Endocrinology, Metabolism and Diabetes Molecular Nutrition Unit Center for Innovative Medicine Huddinge Sweden"},{"name":"KI\/AZ Integrated CardioMetabolic Center Department of Medicine Karolinska Institutet at Karolinska University Hospital Huddinge Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aur\u00e9lien","family":"Thomas","sequence":"additional","affiliation":[{"name":"Unit of Toxicology University Centre of Legal Medicine Lausanne Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie\u2010Claude","family":"Brulhart\u2010Meynet","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Diabetology, Hypertension and Nutrition Department of Internal Medicine Specialities Medical Faculty Geneva University Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estelle","family":"Lauer","sequence":"additional","affiliation":[{"name":"Unit of Toxicology University Centre of Legal Medicine Lausanne Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Frej","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine Division of Clinical Chemistry Sk\u00e5ne University Hospital Lund University Malm\u00f6 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f6rn","family":"Dahlb\u00e4ck","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine Division of Clinical Chemistry Sk\u00e5ne University Hospital Lund University Malm\u00f6 Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Stenvinkel","sequence":"additional","affiliation":[{"name":"Division of Renal Medicine Department of Clinical Science, Intervention and Technology Karolinska University Hospital Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard W.","family":"James","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Diabetology, Hypertension and Nutrition Department of Internal Medicine Specialities Medical Faculty Geneva University Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6884-4793","authenticated-orcid":false,"given":"Miguel A.","family":"Frias","sequence":"additional","affiliation":[{"name":"Division of Endocrinology Diabetology, Hypertension and Nutrition Department of Internal Medicine Specialities Medical Faculty Geneva University Geneva Switzerland"},{"name":"Division of Laboratory Medicine Department of Genetics and Laboratory Medicine Geneva University Hospitals Geneva Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,12,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30788-2"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0158765"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2796.2010.02269.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa041031"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2015.180"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.01.005"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.300935"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013050482"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.114.304172"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.02.009"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2013.02.003"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119664"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.607135"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp289"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.307049"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.07.057"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1797.2012.01572.x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00600.x"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2011.08.049"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00422.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2009.02234.x"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-015-9008-4"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M700113-JLR200"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2015.06.005"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2008.11.007"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M050021"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gft103"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-10-744060"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.10251011"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.D068866"}],"container-title":["European Journal of Clinical Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Feci.12866","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/eci.12866","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T13:09:10Z","timestamp":1695042550000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/eci.12866"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,14]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1111\/eci.12866"],"URL":"https:\/\/doi.org\/10.1111\/eci.12866","archive":["Portico"],"relation":{},"ISSN":["0014-2972","1365-2362"],"issn-type":[{"type":"print","value":"0014-2972"},{"type":"electronic","value":"1365-2362"}],"subject":[],"published":{"date-parts":[[2017,12,14]]},"article-number":"e12866"}}