{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:29:17Z","timestamp":1760142557096,"version":"build-2065373602"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Transplantation"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Tacrolimus has a narrow therapeutic index with substantial inter\u2010 and intra\u2010patient variability, requiring therapeutic drug monitoring (TDM). Influences beyond genetic and developmental factors need to be better understood. Recent studies among adult patients suggest that hemoglobin affects the apparent clearance (CL\/F) of tacrolimus, whereas this and other potential factors in children are under\u2010investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>After ethics approval, we performed a single\u2010center retrospective cohort study of pediatric renal transplant recipients between January 1, 2004, and June 30, 2018. Patients without tacrolimus therapy or those with concomitant sirolimus were excluded. Apparent clearance (CL\/F) was predicted for this analysis using a regression equation derived from 12\u2010point pharmacokinetic (PK) profiles. The equation allowed for the estimation of the area under the curve (AUC) from trough levels, which were then used to calculate CL\/F. Data were collected from electronic health records, and univariate and multivariate mixed\u2010effect regression analyses were performed to evaluate the impact of hemoglobin, albumin, cholesterol, and HDL on CL\/F.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty\u2010three patients were included. The median age at transplantation was 10\u2009years, 52% were female, and the median tacrolimus AUC was 133\u2009ng\u2022h\/mL. CL\/F correlated with hemoglobin (<jats:italic>n<\/jats:italic>\u2009=\u20091257, <jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.3767, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), HDL\u2010cholesterol (<jats:italic>n<\/jats:italic>\u2009=\u2009236, <jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.3973, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), and total cholesterol (<jats:italic>n<\/jats:italic>\u2009=\u2009373, <jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.1821, <jats:italic>p<\/jats:italic>\u2009=\u20090.0004). In multivariate mixed\u2010effect regression, hemoglobin and cholesterol remained significant predictors of CL\/F.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present study suggests a moderate impact of hemoglobin and cholesterol on tacrolimus CL\/F. Lower hemoglobin appears to increase CL\/F, while higher cholesterol reduces it. These findings highlight the potential value of integrating biochemical parameters into dosing strategies to optimize TDM in pediatric kidney transplant recipients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/petr.70065","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T01:11:43Z","timestamp":1741828303000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hemoglobin and Cholesterol Affect Apparent Tacrolimus Clearance in Pediatric Transplant Recipients\u2014A Retrospective Cohort Study"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8905-7481","authenticated-orcid":false,"given":"Carmen In\u00e9s","family":"Rodr\u00edguez Cuellar","sequence":"first","affiliation":[{"name":"Department of Pediatrics Universidad del Rosario  Bogota Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6848-8933","authenticated-orcid":false,"given":"Mara","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Universidad Nacional Aut\u00f3noma de M\u00e9xico  Mexico City Mexico"},{"name":"Unidad de Investigaci\u00f3n y Diagn\u00f3stico en Nefrolog\u00eda y Metabolismo Mineral \u00d3seo Hospital Infantil de M\u00e9xico Federico G\u00f3mez  Mexico City Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1694-886X","authenticated-orcid":false,"given":"Maria Esther","family":"D\u00edaz Gonz\u00e1lez de Ferris","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of North Carolina at Chapel Hill  Chapel Hill North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1891-6765","authenticated-orcid":false,"given":"Guido","family":"Filler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Schulich School of Medicine &amp; Dentistry  London Ontario Canada"},{"name":"Department of Medicine, Schulich School of Medicine &amp; Dentistry University of Western Ontario  London Ontario Canada"},{"name":"Lilibeth Caberto Kidney Clinical Research Unit, London Health Sciences Centre; and Department of Medicine, Schulich School of Medicine &amp; Dentistry University of Western Ontario  London Ontario Canada"},{"name":"Children's Health Research Institute University of Western Ontario  London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"issue":"3","key":"e_1_2_11_2_1","first-page":"S1","article-title":"KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients","volume":"9","author":"Kidney Disease: Improving Global Outcomes Transplant Work G","year":"2009","journal-title":"American Journal of Transplantation"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.12396"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12703"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3046.2007.00782.x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-200410000-00008"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2003.02008.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/petr.12559"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/petr.12637"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000403"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-015-3303-3"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/03602532.2016.1151037"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-003-1271-5"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/pch\/7.8.525"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0109464"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trre.2011.01.001"},{"key":"e_1_2_11_17_1","first-page":"1","article-title":"Chronic Kidney Disease Stage Affects Small, Dense Low\u2010Density Lipoprotein but Not Glycated Low\u2010Density Lipoprotein in Younger Chronic Kidney Disease Patients: A Cross\u2010Sectional Study","volume":"11","author":"Filler G.","year":"2017","journal-title":"Clinical Kidney Journal"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ki.5001608"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/12.8.1668"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-017-0567-8"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1702588"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200140040-00004"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e3182708edf"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-2277.2012.01513.x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3046.2005.00334.x"}],"container-title":["Pediatric Transplantation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/petr.70065","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T10:29:01Z","timestamp":1760092141000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/petr.70065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,12]]},"references-count":24,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1111\/petr.70065"],"URL":"https:\/\/doi.org\/10.1111\/petr.70065","archive":["Portico"],"relation":{},"ISSN":["1397-3142","1399-3046"],"issn-type":[{"type":"print","value":"1397-3142"},{"type":"electronic","value":"1399-3046"}],"subject":[],"published":{"date-parts":[[2025,3,12]]},"assertion":[{"value":"2024-10-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70065"}}