Faculty Profiles - KUWAHARA Shoji

Papers - KUWAHARA Shoji

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Rice Endosperm Protein Improves the Anti-Inflammatory Effects of High-Density Lipoprotein and Produces Lower Atherosclerotic Lesion Accelerated by the Renal Mass Reduction than Casein in a Mouse Model Reviewed International journal

Ryohei Kaseda,Michihiro Hosojima,Shoji Kuwahara,Hideyuki Kabasawa,Hiroyuki Aoki,Yuki Higuchi,Valentina Kon,Ichiei Narita, Akihiko Saito

Journal of the American Nutrition Association 2022.11

Efficacy of Low-Protein Rice for Dietary Protein Restriction in CKD Patients: A Multicenter, Randomized, Controlled Study Reviewed International journal

Michihiro Hosojima, Hideyuki Kabasawa, Ryohei Kaseda, Tomomi Ishikawa-Tanaka, Yoshitsugu Obi, Toshiko Murayama, Shoji Kuwahara, Yoshiki Suzuki, Ichiei Narita, Akihiko Saito

Kidney360 2022.10

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

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 11 ( 1 ) 2020.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Scientific Reports

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.

DOI： 10.1038/s41598-020-80853-6

Scopus

Other Link： https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85099201373&origin=inward

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

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 19 ( 1 ) 2019.12

Language：English Publishing type：Research paper (scientific journal) Publisher：BMC Cancer

© 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.

DOI： 10.1186/s12885-019-6398-2

Scopus

Other Link： https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85076083752&origin=inward

Rice Endosperm Protein Administration to Juvenile Mice Regulates Gut Microbiota and Suppresses the Development of High-Fat Diet-Induced Obesity and Related Disorders in Adulthood Reviewed International journal

Yuki Higuchi, Michihiro Hosojima, Hideyuki Kabasawa, Shoji Kuwahara, Sawako Goto, Koji Toba, Ryohei Kaseda, Takahiro Tanaka, Nobutaka Kitamura, Hayato Takihara, Shujiro Okuda, Masayuki Taniguchi, Hitoshi Arao, Ichiei Narita, Akihiko Saito

Nutrients 2019.12

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 Reviewed

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 20 ( 1 ) 2019.11

Language：English Publishing type：Research paper (scientific journal) Publisher：BMC nephrology

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.

DOI： 10.1186/s12882-019-1591-8

Scopus

Other Link： https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85075524103&origin=inward

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

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 2018.11

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

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 2017.12

Megalin Blockade with Cilastatin Suppresses Drug-Induced Nephrotoxicity. Reviewed International journal

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 2017.6

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

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 2017.5

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 Reviewed

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

Megalin-Mediated Tubuloglomerular Alterations in High-Fat Diet-Induced Kidney Disease. Reviewed International journal

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 2016.7

The endocytic receptor megalin and its associated proteins in proximal tubule epithelial cells. Reviewed International journal

De S, Kuwahara S, Saito A

Membranes 2014.7

Dietary inorganic phosphorus regulates the intestinal peptide transporter PepT1. Reviewed International journal

Furutani J, Segawa H, Aranami F, Kuwahara S, Sugano M, Bannai K, Yamato H, Ito M, Miyamoto K

Journal of Renal Nutrition 2013.3

Identification and functional analysis of a splice variant of mouse sodium-dependent phosphate transporter Npt2c. Reviewed

Kuwahara S, Aranami F, Segawa H, Onitsuka A, Honda N, Tominaga R, Hanabusa E, Kaneko I, Yamanaka S, Sasaki S, Ohi A, Nomura K, Tatsumi S, Kido S, Ito M, Miyamoto K

THE JOURNAL OF MEDICAL INVESTIGATION 2012

リン酸トランスポーターをめぐる最近の話 Invited

桑原頌治　他

消化と吸収 2012

Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b⁺/⁻ mice. Reviewed International journal

Ohi A, Hanabusa E, Ueda O, Segawa H, Horiba N, Kaneko I, Kuwahara S, Mukai T, Sasaki S, Tominaga R, Furutani J, Aranami F, Ohtomo S, Oikawa Y, Kawase Y, Wada NA, Tachibe T, Kakefuda M, Tateishi H, Matsumoto K, Tatsumi S, Kido S, Fukushima N, Jishage K, Miyamoto K.

American Journal of Physiology-Renal Physiology 2011.11

Sodium-dependent phosphate cotransporters: lessons from gene knockout and mutation studies. Reviewed International journal

Miyamoto K, Haito-Sugino S, Kuwahara S, Ohi A, Nomura K, Ito M, Kuwahata M, Kido S, Tatsumi S, Kaneko I, Segawa H.

Journal of Pharmaceutical Sciences 2011

Hypophosphatemia in vitamin D receptor null mice: effect of rescue diet on the developmental changes in renal Na+ -dependent phosphate cotransporters. Reviewed International journal

Kaneko I, Segawa H, Furutani J, Kuwahara S, Aranami F, Hanabusa E, Tominaga R, Giral H, Caldas Y, Levi M, Kato S, Miyamoto K.

Pflugers Archiv: European Journal of Physiology 2011

Phosphaturic action of fibroblast growth factor 23 in Npt2 null mice. Reviewed International journal

Tomoe Y, Segawa H, Shiozawa K, Kaneko I, Tominaga R, Hanabusa E, Aranami F, Furutani J, Kuwahara S, Tatsumi S, Matsumoto M, Ito M, Miyamoto K.

American Journal of Physiology-Renal Physiology 2010.6

Fibroblast growth factor 23 mediates the phosphaturic actions of cadmium. Reviewed

Aranami F, Segawa H, Furutani J, Kuwahara S, Tominaga R, Hanabusa E, Tatsumi S, Kido S, Ito M, Miyamoto K.

THE JOURNAL OF MEDICAL INVESTIGATION 2010.2

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Papers - KUWAHARA Shoji