{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:03:20Z","timestamp":1780470200748,"version":"3.54.1"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004948","name":"Astellas Pharma","doi-asserted-by":"publisher","award":["TransplantLines Biobank and Cohort study"],"award-info":[{"award-number":["TransplantLines Biobank and Cohort study"]}],"id":[{"id":"10.13039\/501100004948","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007560","name":"Chiesi Farmaceutici","doi-asserted-by":"publisher","award":["(PA-SP\/PRJ 2020-9136"],"award-info":[{"award-number":["(PA-SP\/PRJ 2020-9136"]}],"id":[{"id":"10.13039\/100007560","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["14939"],"award-info":[{"award-number":["14939"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016238","name":"Ministerie van Economische Zaken en Klimaat","doi-asserted-by":"publisher","award":["PPP-2019-032"],"award-info":[{"award-number":["PPP-2019-032"]}],"id":[{"id":"10.13039\/501100016238","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016238","name":"Ministerie van Economische Zaken en Klimaat","doi-asserted-by":"publisher","award":["PPP-2022-015"],"award-info":[{"award-number":["PPP-2022-015"]}],"id":[{"id":"10.13039\/501100016238","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["ELIMINATE-CKD, ERC-COG 101125516"],"award-info":[{"award-number":["ELIMINATE-CKD, ERC-COG 101125516"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Transplant."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Kidney transplantation is the only curative treatment for end-stage kidney disease, providing markedly improved outcomes over dialysis. In search of optimized long-term outcomes, recent studies have demonstrated alterations in the metabolic state of kidney transplant recipients (KTRs) may contribute to chronic graft outcomes. Here, we sought to benchmark metabolic perturbations associated with the post-transplant state using a set of extensively characterized kidney transplant donors as healthy control.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this cross-sectional, single-center study, we used untargeted GC-MS to profile the 24\u2005h urine from 121 stable KTRs (0.2\u201338.9 yrs post-transplant) and 94 extensively screened healthy potential kidney donors (HC) from the TransplantLines Biobank and Cohort Study. We assessed group differences using linear models adjusted for baseline covariates including eGFR, and the multivariable OPLS-DA model for global separation. ROC analysis was performed on the top discriminants. GlobalTest Pathway enrichment was used to map differentially abundant metabolites in metabolic pathways from the KEGG database.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In KTRs, 28 metabolites were significantly altered compared to HC; 13 of which were elevated and 15 decreased in KTRs. Among them, methylmalonic acid (AUROC 0.886), citric acid (AUROC 0.870), and glycolic acid (AUROC 0.804) were all reduced in KTRs and showed the strongest in-sample separation between the groups. OPLS-DA achieved good group separation (R\n                      <jats:sup>2<\/jats:sup>\n                      Y\u2009=\u20090.733, Q\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.621) with no signs of overfitting. Twenty pathways were significantly perturbed, led by the TCA cycle, glyoxylate and dicarboxylate metabolism and branched-chain amino acid degradation. Sensitivity analyses examining alternative normalizations, excluding patients with diabetes or proteinuria, adjusting for statin use, and stratifying by eGFR and transplant vintage, were highly concordant with the main analysis (Spearman\n                      <jats:italic>\u03c1<\/jats:italic>\n                      \u2009&amp;gt;\u20090.87 for all pairwise comparisons).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Urinary metabolic profiles in KTRs are consistent with alterations in TCA cycle, glyoxylate and dicarboxylate metabolism, and branched chain amino acid degradation after transplantation. Although causality cannot be established from this cross-sectional design, these findings may reflect altered energy metabolism in the post-transplant state.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/frtra.2026.1833811","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T06:07:29Z","timestamp":1780466849000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Benchmarking the urinary transplant metabolome of kidney transplant recipients using healthy organ donors"],"prefix":"10.3389","volume":"5","author":[{"given":"Naser B. N.","family":"Shehab","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen","place":["Groningen, Netherlands"]},{"name":"Intelligent Systems Group, Faculty of Science and Engineering, University of Groningen, Bernoulli Institute for Mathematics, Computer Science and Artificial Intelligence","place":["Groningen, Netherlands"]},{"name":"Transplantation Research Center, Division of Nephrology, Department of Internal Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim C. M.","family":"Lammers-Jannink","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen","place":["Groningen, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margriet H.","family":"Riphagen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen","place":["Groningen, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siawosh K.","family":"Eskandari","sequence":"additional","affiliation":[{"name":"Transplantation Research Center, Division of Nephrology, Department of Internal Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamil R.","family":"Azzi","sequence":"additional","affiliation":[{"name":"Transplantation Research Center, Division of Nephrology, Department of Internal Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin H.","family":"de Borst","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen","place":["Groningen, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Bunte","sequence":"additional","affiliation":[{"name":"Intelligent Systems Group, Faculty of Science and Engineering, University of Groningen, Bernoulli Institute for Mathematics, Computer Science and Artificial Intelligence","place":["Groningen, Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan J. 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