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Correlation of prechemotherapy urinary megalin ectodomain (A-megalin) levels with the development of cisplatin-induced nephrotoxicity : a prospective observational study
http://hdl.handle.net/10191/00051810
http://hdl.handle.net/10191/0005181089b6766e-ff57-46b7-a665-bafd53798cfc
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2020-08-31 | |||||
| タイトル | ||||||
| タイトル | Correlation of prechemotherapy urinary megalin ectodomain (A-megalin) levels with the development of cisplatin-induced nephrotoxicity : a prospective observational study | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Chemotherapy | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Cisplatin | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Nephrotoxicity | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Urinary megalin | |||||
| 資源タイプ | ||||||
| 資源 | http://purl.org/coar/resource_type/c_46ec | |||||
| タイプ | thesis | |||||
| その他のタイトル | ||||||
| その他のタイトル | 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 | |||||
| 著者 |
Shoji, Satoshi
× Shoji, Satoshi |
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| 著者別名 | ||||||
| 識別子Scheme | WEKO | |||||
| 識別子 | 178024 | |||||
| 姓名 | 庄子, 聡 | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 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. | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | BMC Cancer. 2019, 19(1), 1170. | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | info:doi/10.1186/s12885-019-6398-2 | |||||
| 権利 | ||||||
| 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/). | |||||
| 著者版フラグ | ||||||
| 値 | ETD | |||||
| 学位名 | ||||||
| 学位名 | 博士(医学) | |||||
| 学位授与機関 | ||||||
| 学位授与機関名 | 新潟大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2020-03-23 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 13101甲第4687号 | |||||
| 学位記番号 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 新大院博(医)甲第921号 | |||||
