{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T19:02:53Z","timestamp":1774033373586,"version":"3.50.1"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,12,31]],"date-time":"2022-12-31T00:00:00Z","timestamp":1672444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2021A1515011308"],"award-info":[{"award-number":["2021A1515011308"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010883","name":"Traditional Chinese Medicine Bureau of Guangdong Province","doi-asserted-by":"publisher","award":["20201302"],"award-info":[{"award-number":["20201302"]}],"id":[{"id":"10.13039\/501100010883","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Study Objective<\/jats:title><jats:p>The pharmacokinetics and pharmacodynamics of tacrolimus (TAC) vary greatly among individuals, hindering its precise utilization. Moreover, effective models for the early prediction of TAC efficacy in patients with nephrotic syndrome (NS) are lacking. We aimed to identify key factors affecting TAC efficacy and develop efficacy prediction models for childhood NS using machine learning algorithms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>This was an observational cohort study of patients with pediatric refractory NS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Guangzhou Women and Children's Medical Center between June 2013 and December 2018.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients<\/jats:title><jats:p>203 patients with pediatric refractory NS were used for model generation and 35 patients were used for model validation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Intervention<\/jats:title><jats:p>All patients regularly received double immunosuppressive therapy comprising TAC and low\u2010dose prednisone or methylprednisolone. In this observational cohort study of 203 pediatric patients with refractory NS, clinical and genetic variables, including single\u2010nucleotide polymorphism (SNPs), were identified. TAC efficacy was evaluated 3\u2009months after administration according to two different evaluation criteria: response or non\u2010response (Group 1) and complete remission, partial remission, or non\u2010remission (Group 2).<\/jats:p><\/jats:sec><jats:sec><jats:title>Measurements<\/jats:title><jats:p>Logistic regression, extremely random trees, gradient boosting decision trees, random forest, and extreme gradient boosting algorithms were used to develop and validate the models. Prediction models were validated among a cohort of 35 patients with NS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Results<\/jats:title><jats:p>The random forest models performed best in both groups, and the area under the receiver operating characteristics curve of these two models was 80.7% (Group 1) and 80.3% (Group 2). These prediction models included urine erythrocyte count before administration, steroid types, and eight SNPs (<jats:italic>ITGB4<\/jats:italic> rs2290460, <jats:italic>TRPC6<\/jats:italic> rs3824934, <jats:italic>CTGF<\/jats:italic> rs9399005, <jats:italic>IL13<\/jats:italic> rs20541, <jats:italic>NFKBIA<\/jats:italic> rs8904, <jats:italic>NFKBIA<\/jats:italic> rs8016947, <jats:italic>MAP3K11<\/jats:italic> rs7946115, and <jats:italic>SMARCAL1<\/jats:italic> rs11886806).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Two pre\u2010administration models with good predictive performance for TAC response of patients with NS were developed and validated using machine learning algorithms. These accurate models could assist clinicians in predicting TAC efficacy in pediatric patients with NS before utilization to avoid treatment failure or adverse effects.<\/jats:p><\/jats:sec>","DOI":"10.1002\/phar.2749","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T20:23:25Z","timestamp":1671135805000},"page":"43-52","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Tacrolimus in the treatment of childhood nephrotic syndrome: Machine learning detects novel biomarkers and predicts efficacy"],"prefix":"10.1002","volume":"43","author":[{"given":"Xiaolan","family":"Mo","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Guangzhou Women and Children's Medical Center Guangzhou Medical University  Guangzhou China"},{"name":"Institute of Clinical Pharmacology, School of Pharmaceutical Sciences Sun Yat\u2010sen University  Guangzhou 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