{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T11:33:38Z","timestamp":1785929618773,"version":"3.56.0"},"reference-count":52,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"European Society for Paediatric Nephrology"},{"name":"Chiesi Deutschland"},{"DOI":"10.13039\/501100010441","name":"Medizinischen Fakult\u00e4t Heidelberg, Universit\u00e4t Heidelberg","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010441","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018936","name":"Universit\u00e4tsklinikum Heidelberg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018936","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Nephrol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Data on the relevance of tacrolimus intrapatient variability (TacIPV) and concentration-to-dose ratio (C\/D ratio) as an approximation of tacrolimus metabolism for predicting outcomes in pediatric kidney transplant (pKTx) recipients are scarce.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a multicenter retrospective study of 255 pKTx recipients from the CERTAIN registry. TacIPV was quantified as the coefficient of variation (CV%) during months 6\u201312 post-transplant. In addition, the C\/D ratio, corrected for body surface area, was calculated for the first 6\u00a0months post-transplant. Cutoffs were determined by minimization of log-rank\n                      <jats:italic>P<\/jats:italic>\n                      values: 23% for TacIPV and 1.0 for C\/D ratio. Rejection episodes were classified according to the Banff criteria in the period following marker quantification.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 13,159 tacrolimus trough blood levels were analyzed, with a median of 52 (IQR, 41\u201363) measurements per patient. High TacIPV (&gt;\u200923%) during months 6\u201312 post-transplant was associated with an increased risk of rejection beyond 12\u00a0months post-transplant (hazard ratio (HR) 1.04, 95% CI 1.01\u20131.06,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.002; Kaplan\u2013Meier analysis\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.002). Similarly, a low C\/D ratio (&lt;\u20091.0), i.e., rapid tacrolimus metabolism, during the first 6\u00a0months was associated with a higher risk of rejection between months 6 and 12 (inverse HR 3.13, 95% CI 1.01\u20139.09,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.04; Kaplan\u2013Meier analysis\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.011).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This largest to date multicenter study determines pediatric-specific cutoff values for TacIPV and tacrolimus C\/D ratio as a predictive marker for graft rejection. Patients with these risk factors should be closely monitored and their immunosuppressive therapy adjusted accordingly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00467-025-06872-5","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T16:38:23Z","timestamp":1753115903000},"page":"3743-3754","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Association of intrapatient tacrolimus variability and concentration-to-dose ratio with outcomes in pediatric kidney transplantation"],"prefix":"10.1007","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8957-7767","authenticated-orcid":false,"given":"Maral","family":"Baghai Arassi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Fisch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5016-9731","authenticated-orcid":false,"given":"Manuel","family":"Fei\u00dft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0409-5196","authenticated-orcid":false,"given":"Kai","family":"Krupka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4131-2273","authenticated-orcid":false,"given":"Britta","family":"H\u00f6cker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9939-4059","authenticated-orcid":false,"given":"Alexander","family":"Fichtner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4865-4906","authenticated-orcid":false,"given":"Nele","family":"Kanzelmeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9732-8656","authenticated-orcid":false,"given":"Jens","family":"K\u00f6nig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8164-6318","authenticated-orcid":false,"given":"Anette","family":"Melk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1846-675X","authenticated-orcid":false,"given":"Jun","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3635-6418","authenticated-orcid":false,"given":"Lars","family":"Pape","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4116-598X","authenticated-orcid":false,"given":"Lutz T.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1696-5646","authenticated-orcid":false,"given":"Marcus","family":"Weitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6598-6910","authenticated-orcid":false,"given":"Burkhard","family":"T\u00f6nshoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the CERTAIN Research Network, the ESPN working group on transplantation","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,21]]},"reference":[{"key":"6872_CR1","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1097\/TP.0b013e3182708ea8","volume":"95","author":"A Gondos","year":"2013","unstructured":"Gondos A, D\u00f6hler B, Brenner H, Opelz G (2013) Kidney graft survival in Europe and the United States: strikingly different long-term outcomes. 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