桑原 頌治 (クワハラ ショウジ)

KUWAHARA Shoji

写真a

職名

講師

研究分野・キーワード

栄養、腎臓

学内職務経歴 【 表示 / 非表示

  • 滋賀県立大学  人間文化学部  生活栄養学科  講師   2019年04月 ~ 現在

  • 滋賀県立大学  人間文化学部  生活栄養学科  助教   2018年11月 ~ 2019年03月

所属学会・委員会 【 表示 / 非表示

  • 日本栄養・食糧学会  

 

論文 【 表示 / 非表示

  • Combination therapy of cisplatin with cilastatin enables an increased dose of cisplatin, enhancing its antitumor effect by suppression of nephrotoxicity

    Arita M., Watanabe S., Aoki N., Kuwahara S., Suzuki R., Goto S., Abe Y., Takahashi M., Sato M., Hokari S., Ohtsubo A., Shoji S., Nozaki K., Ichikawa K., Kondo R., Hayashi M., Ohshima Y., Kabasawa H., Hosojima M., Koya T., Saito A., Kikuchi T.

    Scientific Reports  Scientific Reports  11 (1)    2020年12月

    10.1038/s41598-020-80853-6  共著  

    [概要]

    Cisplatin, one of the most active anticancer agents, is widely used in standard chemotherapy for various cancers. Cisplatin is more poorly tolerated than other chemotherapeutic drugs, and the main dose-limiting toxicity of cisplatin is its nephrotoxicity, which is dose-dependent. Although less toxic methods of cisplatin administration have been established, cisplatin-induced nephrotoxicity remains an unsolved problem. Megalin is an endocytic receptor expressed at the apical membrane of proximal tubules. We previously demonstrated that nephrotoxic drugs, including cisplatin, are reabsorbed through megalin and cause proximal tubular cell injury. We further found that cilastatin blocked the binding of cisplatin to megalin in vitro. In this study, we investigated whether cilastatin could reduce cisplatin-induced nephrotoxicity without influencing the antitumor effects of cisplatin. Nephrotoxicity was decreased or absent in mice treated with cisplatin and cilastatin, as determined by kidney injury molecule-1 staining and the blood urea nitrogen content. Combined with cilastatin, a twofold dose of cisplatin was used to successfully treat the mice, which enhanced the antitumor effects of cisplatin but reduced its nephrotoxicity. These findings suggest that we can increase the dose of cisplatin when combined with cilastatin and improve the outcome of cancer patients.

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

    Shoji S., Hosojima M., Kabasawa H., Kondo R., Miura S., Watanabe S., Aoki N., Kaseda R., Kuwahara S., Tanabe N., Hirayama Y., Narita I., Kikuchi T., Kagamu H., Saito A.

    BMC Cancer  BMC Cancer  19 (1)    2019年12月

    10.1186/s12885-019-6398-2  共著  

    [概要]

    © 2019 The Author(s). 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 receive chemotherapy 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, β2-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.

  • Higher estimated net endogenous acid production with lower intake of fruits and vegetables based on a dietary survey is associated with the progression of chronic kidney disease

    Toba K., Hosojima M., Kabasawa H., Kuwahara S., Murayama T., Yamamoto-Kabasawa K., Kaseda R., Wada E., Watanabe R., Tanabe N., Suzuki Y., Narita I., Saito A.

    BMC nephrology  BMC nephrology  20 (1)    2019年11月

    10.1186/s12882-019-1591-8  共著  

    [概要]

    BACKGROUND: Dietary acid load has been suggested to mediate the progression of chronic kidney disease (CKD). However, it is unclear what kinds of foods are actually associated with dietary acid load in patients with CKD. The self-administered diet history questionnaire (DHQ), which semi-quantitatively assesses the dietary habits of Japanese individuals through 150 question items, can estimate average daily intake of various foods and nutrients during the previous month. Using the DHQ, we investigated the association of dietary acid load with CKD progression. We also analyzed the kinds of food that significantly affect dietary acid load. METHODS: Subjects were 96 outpatients with CKD (average estimated glomerular filtration rate [eGFR], 53.0 ± 18.1 ml/min/1.73 m2) at Niigata University Hospital, who had completed the DHQ in 2011. We calculated net endogenous acid production (NEAP) from potassium and protein intake evaluated by the DHQ in order to assess dietary acid load. CKD progression was assessed by comparing eGFR between 2008 and 2014. RESULTS: NEAP was not correlated with protein intake (r = 0.088, p = 0.398), but was negatively correlated with potassium intake (r = - 0.748, p < 0.001). Reduction in eGFR from 2008 to 2014 was estimated to be significantly greater in patients with higher NEAP (NEAP > 50.1 mEq/day, n = 45) than in those with lower NEAP (NEAP ≤50.1 mEq/day, n = 50) by 5.9 (95% confidence interval [95%CI], 0.1 to 11.6) ml/min/1.73 m2. According to multiple logistic regression analysis, higher NEAP was significantly associated with lower intake of fruits (odds ratio [OR], 6.454; 95%CI, 2.19 to 19.00), green and yellow vegetables (OR, 5.18; 95%CI, 1.83 to14.66), and other vegetables (OR, 3.87; 95%CI, 1.29 to 11.62). CONCLUSIONS: Elevated NEAP could be a risk factor for CKD progression. Low intake of fruits and vegetables would increase dietary acid load and might affect the progression of renal dysfunction in Japanese CKD patients.

  • Circulating FABP4 is eliminated by the kidney via glomerular filtration followed by megalin-mediated reabsorption.

    Suman Shrestha, Hiroaki Sunaga, Hirofumi Hanaoka, Aiko Yamaguchi, Shoji Kuwahara, Yogi Umbarawan, Kiyomi Nakajima, Tetsuo Machida, Masami Murakami, Akihiko Saito, Yoshito Tsushima, Masahiko Kurabayashi, Tatsuya Iso

     SCIENTIFIC REPORTS    2018年11月

    共著  共同(副担当)

  • A Randomized, Double-Blind, Crossover Pilot Trial of Rice Endosperm Protein Supplementation in Maintenance Hemodialysis Patients.

    Michihiro Hosojima, Hisaki Shimada, Yoshitsugu Obi, Shoji Kuwahara, Ryohei Kaseda, Hideyuki Kabasawa, Hazuki Kondo, Mikio Fujii, Reiko Watanabe, Yoshiki Suzuki, Motoni Kadowaki, Shigeru Miyazaki, Akihiko Saito

     SCIENTIFIC REPORTS    2017年12月

    共著  共同(主担当)

  • Megalin Blockade with Cilastatin Suppresses Drug-Induced Nephrotoxicity.

    Yoshihisa Hori, Nobumasa Aoki, Shoji Kuwahara, Michihiro Hosojima, Ryohei Kaseda, Sawako Goto, Tomomichi Iida, Shankhajit De, Hideyuki Kabasawa, Reika Kaneko, Hiroyuki Aoki, Yoshinari Tanabe, Hiroshi Kagamu, Ichiei Narita, Toshiaki Kikuchi, Akihiko Saito

     Journal of the American Society of Nephrology    2017年06月

    共著  共同(主担当)

  • Exocytosis-Mediated Urinary Full-Length Megalin Excretion Is Linked With the Pathogenesis of Diabetic Nephropathy.

    De S, Kuwahara S, Hosojima M, Ishikawa T, Kaseda R, Sarkar P, Yoshioka Y, Kabasawa H, Iida T, Goto S, Toba K, Higuchi Y, Suzuki Y, Hara M, Kurosawa H, Narita I, Hirayama Y, Ochiya T, Saito A

     Diabetes    2017年05月

    共著  共同(主担当)

  • SGLT2阻害薬開始前後で食事記録を確認できた肥満2型糖尿病患者の一例

    和田恵梨, 細島康宏, 蒲澤秀門, 石川友美, 桑原頌治, 忰田亮平, 成田一衛, 本間則行, 鈴木芳樹, 斎藤亮彦

     日本病態栄養学会誌    2017年

    共著  共同(副担当)

  • Megalin-Mediated Tubuloglomerular Alterations in High-Fat Diet-Induced Kidney Disease.

    Kuwahara S, Hosojima M, Kaneko R, Aoki H, Nakano D, Sasagawa T, Kabasawa H, Kaseda R, Yasukawa R, Ishikawa T, Suzuki A, Sato H, Kageyama S, Tanaka T, Kitamura N, Narita I, Komatsu M, Nishiyama A, Saito A

     Journal of the American Society of Nephrology    2016年07月

    共著  共同(主担当)

  • The endocytic receptor megalin and its associated proteins in proximal tubule epithelial cells.

    De S, Kuwahara S, Saito A

     Membranes    2014年07月

    共著  共同(主担当)

全件表示 >>

著書 【 表示 / 非表示

  • エキスパート管理栄養士養成シリーズ基礎栄養学[第5版]

    坂井堅太郎 編

    化学同人  210p  2021年02月

    教科書  共著

  • 糖尿病性腎症病期分類に基づいた腎病理診断の手引き

    和田隆志、湯澤由紀夫、乳原善文、古市賢吾 編集

    東京医学社  2019年04月

    調査報告書  共著

総説・解説記事 【 表示 / 非表示

  • 腎疾患におけるエクソソームバイオマーカー

    細島康宏、蒲澤秀門、桑原頌治、斎藤亮彦

     CLINICAL CALCIUM    2018年02月

     共著  共同(副担当)

  • メガリンをターゲットとした慢性腎臓病の新規治療法の開発

    桑原頌治、細島康宏、蒲澤秀門、忰田亮平、斎藤亮彦

     腎と骨代謝    2018年

     共著  共同(主担当)

  • 腎障害の「入り口」分子としてのメガリン

    桑原 頌治、細島 康宏、蒲澤 秀門、 忰田 亮平、斎藤 亮彦

     腎臓内科・泌尿器科    2017年

     共著  共同(主担当)

  • メガリンを入り口とした腎障害機序とそれに基づく診断・治療法の開発

    桑原 頌治, 細島 康宏, 斎藤 亮彦

     臨床病理    2017年

     共著  共同(主担当)

  • 近位尿細管細胞と蛋白尿

    桑原頌治, 細島康宏, 忰田亮平, 斎藤亮彦

     腎と透析    2016年

     共著  共同(主担当)

  • タンパク質代謝臓器としての腎

    富野康日己、柏原 直樹 他

     In: Annual Review 腎臓 2015    2015年01月

     共著  共同(主担当)

  • メガリンとその関連分子をめぐる最近の話題

    富野 康日己, 成田 一衛, 柏原 直樹 他

     In: Annual Review 腎臓 2014    2014年

     共著  共同(主担当)

  • メガリンとCKD

    桑原 頌治 , 細島 康宏 , 斎藤 亮彦

     腎と骨代謝    2013年07月

     共著  共同(主担当)

  • FGF23およびklothoによる尿細管でのリン輸送制御機構

    桑原頌治, 野村憲吾, 大井彰子, 宮本賢一

     腎と透析    2012年

     共著  共同(主担当)

  • 栄養・食品機能とトランスポーター

    竹谷豊、 薩秀夫、 伊藤美紀子、 武田英二  他

     栄養・食品機能とトランスポーター    2011年05月

     共著  共同(副担当)

全件表示 >>

研究シーズ 【 表示 / 非表示

  • リンの代謝調節機構の解明と健康