{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:02:45Z","timestamp":1787022165158,"version":"build-2736575974"},"reference-count":74,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T00:00:00Z","timestamp":1736899200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004348","name":"Stockholms L\u00e4ns Landsting","doi-asserted-by":"publisher","award":["2020 and 2021"],"award-info":[{"award-number":["2020 and 2021"]}],"id":[{"id":"10.13039\/501100004348","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008035","name":"Njurfonden","doi-asserted-by":"publisher","award":["F2017\u20130048"],"award-info":[{"award-number":["F2017\u20130048"]}],"id":[{"id":"10.13039\/501100008035","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2021-02251_VR"],"award-info":[{"award-number":["2021-02251_VR"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The causes of reduced aerobic exercise capacity (ExCap) in chronic kidney disease (CKD) are multifactorial, possibly involving the accumulation of tryptophan (TRP) metabolites such as kynurenine (KYN) and kynurenic acid (KYNA), known as kynurenines. Their relationship to ExCap has yet to be studied in CKD. We hypothesised that aerobic ExCap would be negatively associated with plasma levels of TRP, KYN and KYNA in CKD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We included 102 patients with non-dialysis CKD stages 2\u20135 (CKD 2\u20133, n = 54; CKD 4\u20135, n = 48) and 54 healthy controls, age- and sex-matched with the CKD 2\u20133 group. ExCap was assessed as peak workload during a maximal cycle ergometer test. Plasma KYN, KYNA and TRP were determined by high-performance liquid chromatography. Kidney function was evaluated by glomerular filtration rate (GFR) and estimated GFR. The CKD 2\u20133 group and healthy controls repeated tests after five years. The association between TRP, KYN, KYNA and ExCap in CKD was assessed using a generalised linear model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At baseline, there were significant differences between all groups in aerobic ExCap, KYN, KYNA, TRP and KYN\/TRP. KYNA increased in CKD 2\u20133 during the follow-up period. In CKD 2\u20135, KYNA, KYN\/TRP and KYNA\/KYN were all significantly negatively associated with ExCap at baseline, whereas KYN and TRP were not. Kynurenines were significantly correlated with GFR (p &lt; 0.001 for all). Including GFR in the statistical model, no kynurenines were independently associated with ExCap at baseline. At follow-up, the increase in KYN and KYN\/TRP was related to a decrease in ExCap in CKD 2\u20133. After adjusting for GFR, increase in KYN\/TRP remained an independent significant predictor of a decline in ExCap in CKD 2\u20133.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Aerobic ExCap was inversely associated with plasma levels of kynurenines in CKD at baseline and follow-up.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0317201","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T13:37:30Z","timestamp":1736948250000},"page":"e0317201","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Kynurenines and aerobic exercise capacity in chronic kidney disease: A cross-sectional and longitudinal study"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9187-2426","authenticated-orcid":true,"given":"Helena","family":"Wallin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Jansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Erhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7063-2925","authenticated-orcid":true,"given":"Carin","family":"Wallquist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Britta","family":"Hylander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan H.","family":"Jacobson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5079-9696","authenticated-orcid":true,"given":"Kenneth","family":"Caidahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anette","family":"Rickenlund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria J.","family":"Eriksson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"issue":"2","key":"pone.0317201.ref001","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1111\/j.1523-1755.2004.00411.x","article-title":"Exercise capacity as a predictor of survival among ambulatory patients with end-stage renal disease","volume":"65","author":"KE Sietsema","year":"2004","journal-title":"Kidney Int"},{"issue":"4","key":"pone.0317201.ref002","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1002\/pri.287","article-title":"Living with chronic renal failure: patients\u2019 experiences of their physical and functional capacity","volume":"8","author":"S Heiwe","year":"2003","journal-title":"Physiother Res Int"},{"issue":"4","key":"pone.0317201.ref003","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.jsams.2014.07.005","article-title":"Cardiorespiratory fitness and cardiovascular burden in chronic kidney disease","volume":"18","author":"EJ Howden","year":"2015","journal-title":"J Sci Med Sport"},{"issue":"12","key":"pone.0317201.ref004","doi-asserted-by":"crossref","first-page":"e0209325","DOI":"10.1371\/journal.pone.0209325","article-title":"Gradual reduction in exercise capacity in chronic kidney disease is associated with systemic oxygen delivery factors","volume":"13","author":"H Wallin","year":"2018","journal-title":"PLoS One"},{"issue":"12","key":"pone.0317201.ref005","doi-asserted-by":"crossref","first-page":"2064","DOI":"10.1093\/ndt\/gfw303","article-title":"Impaired vascular function contributes to exercise intolerance in chronic kidney disease","volume":"31","author":"AH Van Craenenbroeck","year":"2016","journal-title":"Nephrol Dial Transplant"},{"issue":"2","key":"pone.0317201.ref006","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1053\/j.ajkd.2015.02.335","article-title":"Reduced Cardiovascular Reserve in Chronic Kidney Failure: A Matched Cohort Study","volume":"66","author":"SM Ting","year":"2015","journal-title":"Am J Kidney Dis"},{"issue":"7","key":"pone.0317201.ref007","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1681\/ASN.2020091319","article-title":"Cardiac and Noncardiac Determinants of Exercise Capacity in CKD","volume":"32","author":"S Chinnappa","year":"2021","journal-title":"J Am Soc Nephrol"},{"issue":"6","key":"pone.0317201.ref008","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1053\/j.ackd.2009.09.002","article-title":"Determinants of exercise capacity in CKD patients treated with hemodialysis","volume":"16","author":"P. 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