{"created":"2021-03-01T06:40:27.477137+00:00","id":34012,"links":{},"metadata":{"_buckets":{"deposit":"6e4ee462-d9ca-4224-9297-5cc9d0cb973c"},"_deposit":{"id":"34012","owners":[],"pid":{"revision_id":0,"type":"depid","value":"34012"},"status":"published"},"_oai":{"id":"oai:niigata-u.repo.nii.ac.jp:00034012","sets":["453:455","471:561:562"]},"item_6_alternative_title_1":{"attribute_name":"その他のタイトル","attribute_value_mlt":[{"subitem_alternative_title":"化学療法前尿中Aメガリン値とシスプラチンによる腎障害発症の相関性 : 前向き観察研究"}]},"item_6_date_granted_51":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2020-03-23"}]},"item_6_degree_grantor_49":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_name":"新潟大学"}]}]},"item_6_degree_name_48":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士(医学)"}]},"item_6_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Background: Cisplatin is a potent chemotherapeutic agent used to treat a variety of solid tumors. One of the major side effects of cisplatin is dose-limiting nephrotoxicity. We recently demonstrated that the renal uptake of cisplatin and resultant cisplatin-induced nephrotoxicity are mediated in part by megalin, an endocytic receptor in proximal tubule epithelial cells (PTECs). We also developed sandwich enzyme-linked immunosorbent assays to measure the megalin ectodomain (A-megalin) and full-length megalin (C-megalin) in urine using monoclonal antibodies against the amino and carboxyl-termini of megalin, respectively. The present study examined the correlation of urinary megalin level with cisplatin-induced nephrotoxicity and its utility as a biomarker in patients with thoracic cancer. Methods: This prospective observational study involved 45 chemotherapy-naïve patients scheduled to receivechemo therapy with ≥ 60 mg/m2 cisplatin for histologically diagnosed small cell lung cancer, non-small cell lung cancer, or malignant pleural mesothelioma. Before and after the first course of chemotherapy, we measured urinary A- and C-megalin and other markers of PTEC injury, such as N-acetyl-β-D-glucosaminidase, α1-microglobulin, β_2-microglobulin, neutrophil gelatinase-associated lipocalin, and liver-type fatty acid-binding protein, and compared the values with the change in the estimated glomerular filtration rate (eGFR) and clinical risk factors for renal impairment. Results: A negative correlation was found between baseline urinary A-megalin levels and change in eGFR (r = − 0.458, P = 0.002). According to Kaplan–Meier survival curves, eGFR decline was associated with the baseline urinary A-megalin quartile (P = 0.038). In addition, according to the hazard ratios (HRs) for eGFR decline > 10 mL/min/1.73 m2 calculated using a Cox proportional hazard model, the highest quartile had a significantly higher risk of eGFR decline compared with the lowest quartile (HR 7.243; 95% confidence interval 1.545–33.962). Other baseline urinary markers showed no correlation with eGFR decline. Conclusions: This is the first report demonstrating that prechemotherapy urinary A-megalin levels are correlated with the development of cisplatin-induced nephrotoxicity. This finding has clinical implications for the identification of patients at risk for cisplatin-induced nephrotoxicity and the development of possible prophylactic therapies.","subitem_description_type":"Abstract"}]},"item_6_description_5":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"BMC Cancer. 2019, 19(1), 1170.","subitem_description_type":"Other"}]},"item_6_description_53":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_description":"新大院博(医)甲第921号","subitem_description_type":"Other"}]},"item_6_dissertation_number_52":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"13101甲第4687号"}]},"item_6_full_name_3":{"attribute_name":"著者別名","attribute_value_mlt":[{"nameIdentifiers":[{"nameIdentifier":"178024","nameIdentifierScheme":"WEKO"}],"names":[{"name":"庄子, 聡"}]}]},"item_6_relation_14":{"attribute_name":"DOI","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"info:doi/10.1186/s12885-019-6398-2","subitem_relation_type_select":"DOI"}}]},"item_6_rights_15":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"【○!C】 The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)."}]},"item_6_select_19":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_select_item":"ETD"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"Shoji, Satoshi"}],"nameIdentifiers":[{"nameIdentifier":"178023","nameIdentifierScheme":"WEKO"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-08-31"}],"displaytype":"detail","filename":"r1nmk921.pdf","filesize":[{"value":"618.3 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"本文","url":"https://niigata-u.repo.nii.ac.jp/record/34012/files/r1nmk921.pdf"},"version_id":"21579135-ab43-47e9-a713-282efe0750a3"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-08-31"}],"displaytype":"detail","filename":"r1nmk921_a.pdf","filesize":[{"value":"571.0 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"要旨","url":"https://niigata-u.repo.nii.ac.jp/record/34012/files/r1nmk921_a.pdf"},"version_id":"342de421-6cbf-4464-8090-4dce047ac92f"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Chemotherapy","subitem_subject_scheme":"Other"},{"subitem_subject":"Cisplatin","subitem_subject_scheme":"Other"},{"subitem_subject":"Nephrotoxicity","subitem_subject_scheme":"Other"},{"subitem_subject":"Urinary megalin","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"thesis","resourceuri":"http://purl.org/coar/resource_type/c_46ec"}]},"item_title":"Correlation of prechemotherapy urinary megalin ectodomain (A-megalin) levels with the development of cisplatin-induced nephrotoxicity : a prospective observational study","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Correlation of prechemotherapy urinary megalin ectodomain (A-megalin) levels with the development of cisplatin-induced nephrotoxicity : a prospective observational study"}]},"item_type_id":"6","owner":"1","path":["455","562"],"pubdate":{"attribute_name":"公開日","attribute_value":"2020-08-31"},"publish_date":"2020-08-31","publish_status":"0","recid":"34012","relation_version_is_last":true,"title":["Correlation of prechemotherapy urinary megalin ectodomain (A-megalin) levels with the development of cisplatin-induced nephrotoxicity : a prospective observational study"],"weko_creator_id":"1","weko_shared_id":null},"updated":"2022-12-15T04:04:21.451536+00:00"}