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

• Material Type: 博士論文
• Title: Correlation of prechemotherapy urinary megalin ectodomain (A-megalin) levels with the development of cisplatin-induced nephrotoxicity : a prospective observational study
• Author/Editor: Shoji, Satoshi
• Publication Date: 2020-03-23
• Publication Date (W3CDTF): 2020-03-23
• 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
• Degree Grantor: 新潟大学
• Date Granted: 2020-03-23
• Date Granted (W3CDTF): 2020-03-23
• Dissertation Number: 甲第4687号
• Degree Type: 博士(医学)
• Conferring No. (Dissertation): 甲第4687号
• Text Language Code: eng
• Subject Heading: Chemotherapy; Cisplatin; Nephrotoxicity; Urinary megalin
• Note (General): 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
• Persistent ID (NDL): info:ndljp/pid/11538615; https://dl.ndl.go.jp/pid/11538615
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• Date Accepted (W3CDTF): 2020-09-07T06:04:08+09:00
• Date Created (W3CDTF): 2020-08-31
• Format (IMT): application/pdf
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• Periodical Title (URI): http://hdl.handle.net/10191/00051810
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