{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:50:41Z","timestamp":1778154641760,"version":"3.51.4"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Transplant Infectious Dis"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Valganciclovir (VGCV) prophylaxis effectively prevents cytomegalovirus infection in lung transplant patients. However, VGCV\u2010induced neutropenia causes early cessation. Nucleoside diphosphate\u2010linked moiety X\u2010type motif (NUDT) 15 degrades the ganciclovir (GCV) triphosphate, an active metabolite. We assessed the effects of\n                      <jats:italic>NUDT15<\/jats:italic>\n                      variants on neutropenia and VGCV cessation in recipients of lung transplants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We recruited 28 patients who had received lung transplants and VGCV prophylaxis and genotyped\n                      <jats:italic>NUDT15<\/jats:italic>\n                      exons 1\u20133 using Sanger sequencing. Neutrophil counts were monitored from 1 month to 1 year in the wild\u2010type and NUDT15 reduced\u2010function variant groups. Cumulative incidences of neutropenia (&lt;\u00a01500\/mm\n                      <jats:sup>3<\/jats:sup>\n                      ) and neutropenia\u2010related cessation within 1 year, including late\u2010onset neutropenia, were assessed using Kaplan\u2013Meier analysis. A subgroup analysis was conducted focusing on patients with stable renal function, the primary route of excretion for GCV.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 28 patients, nine carried\n                      <jats:italic>NUDT15<\/jats:italic>\n                      variants (Arg139Cys, Val18Ile, Val18_Val19insGlyVal, Arg139Cys\/Val18Ile). The neutrophil count nadir within 1 month of treatment was lower in the NUDT15\u2010variant group than in the wild\u2010type group. A higher incidence of neutropenia and VGCV cessation was observed in the NUDT15\u2010variant group, but without statistical significance. Among 13 patients with stable renal function, all four in the NUDT15\u2010variant group developed neutropenia and cessation within 60 days, compared with two of nine in the wild\u2010type group. Covariance analysis showed that\n                      <jats:italic>NUDT15<\/jats:italic>\n                      variants were associated with decreased neutrophil counts, independent of GCV trough concentration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>NUDT15<\/jats:italic>\n                      variants increase the risk of early neutropenia during VGCV prophylaxis in lung transplant recipients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/tid.70108","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T06:11:39Z","timestamp":1758262299000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<i>NUDT15<\/i>\n                    Genetic Polymorphism as a Risk Factor for Early Neutropenia During Valganciclovir Prophylaxis in Lung Transplant Patients"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3003-3238","authenticated-orcid":false,"given":"Yurie","family":"Katsube","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Umemura","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuzuki","family":"Urabe","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miori","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiki","family":"Katada","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"},{"name":"Department of Infection Control and Prevention Kyoto University Hospital  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiki","family":"Hira","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Ohsumi","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Tsuda","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"},{"name":"Department of Clinical Pharmacy and Education Graduate School of Pharmaceutical Sciences Kyoto University  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunsaku","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyuki","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Division of Translational and Clinical Pharmacology Cincinnati Children's Hospital Medical Center  Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati College of Medicine  Cincinnati Ohio USA"},{"name":"Department of Pharmacometrics and Systems Pharmacology Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miki","family":"Nagao","sequence":"additional","affiliation":[{"name":"Department of Infection Control and Prevention Kyoto University Hospital  Kyoto Japan"},{"name":"Department of Clinical Laboratory Medicine Graduate School of Medicine Kyoto University  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Date","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Education Graduate School of Pharmaceutical Sciences Kyoto University  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiro","family":"Terada","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,18]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw668"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2004.00505.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00408-022-00551-0"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000005374"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/icvts\/ivx226"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/tid.14141"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40780-024-00352-y"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/358162a0"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv342"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2021.06.001"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24509-7"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-018-1486-7"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3060"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/cc2872"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2024.07.010"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2015.43"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16600"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.16600"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2730"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v30.i12.1751"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0000000000000925"}],"container-title":["Transplant Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/tid.70108","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/tid.70108","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/tid.70108","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T08:34:08Z","timestamp":1768206848000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/tid.70108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,18]]},"references-count":21,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1111\/tid.70108"],"URL":"https:\/\/doi.org\/10.1111\/tid.70108","archive":["Portico"],"relation":{},"ISSN":["1398-2273","1399-3062"],"issn-type":[{"value":"1398-2273","type":"print"},{"value":"1399-3062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,18]]},"assertion":[{"value":"2025-09-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication 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