Correlation of prechemotherapy urinary megalin ectodomain (A-megalin) levels with the development of cisplatin-induced nephrotoxicity : a prospective observational study

• 資料種別: 博士論文
• タイトル: Correlation of prechemotherapy urinary megalin ectodomain (A-megalin) levels with the development of cisplatin-induced nephrotoxicity : a prospective observational study
• 著者・編者: Shoji, Satoshi
• 出版年月日等: 2020-03-23
• 出版年（W3CDTF）: 2020-03-23
• 並列タイトル等: 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
• 授与機関名: 新潟大学
• 授与年月日: 2020-03-23
• 授与年月日（W3CDTF）: 2020-03-23
• 報告番号: 甲第4687号
• 学位: 博士(医学)
• 博論授与番号: 甲第4687号
• 本文の言語コード: eng
• 件名標目: Chemotherapy; Cisplatin; Nephrotoxicity; Urinary megalin
• 一般注記: 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.; BMC Cancer. 2019, 19(1), 1170.; 新大院博(医)甲第921号; 元資料の権利情報 : 【○!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/).
• DOI: info:doi/10.1186/s12885-019-6398-2; https://doi.org/info:doi/10.1186/s12885-019-6398-2
• 国立国会図書館永続的識別子: info:ndljp/pid/11538615; https://dl.ndl.go.jp/pid/11538615
• コレクション（共通）: 障害者向け資料
• コレクション（障害者向け資料：レベル1）: テキストデータ
• コレクション（個別）: 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• 収集根拠: 博士論文（自動収集）
• 受理日（W3CDTF）: 2020-09-07T06:04:08+09:00
• 作成日（W3CDTF）: 2020-08-31
• 記録形式（IMT）: application/pdf
• オンライン閲覧公開範囲: 国立国会図書館内限定公開
• デジタル化資料送信: 図書館・個人送信対象外
• 遠隔複写可否（NDL）: 可
• 掲載誌（URI）: http://hdl.handle.net/10191/00051810
• 連携機関・データベース: 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp