Updated on 2023/02/05

写真a

 
TANAKA Mototsugu
 
Organization
University Medical and Dental Hospital Clinical and Translational Research Center Associate Professor
Title
Associate Professor
Contact information
メールアドレス
External link

Degree

  • 博士(医学) ( 2015.3 )

Research Interests

  • Bacteriology

  • Regulatory Science

  • Clinical pharmacology

  • Nephrology

  • Hemodialysis

  • Peritoneal dialysis

Research Areas

  • Life Science / Clinical pharmacy  / Regulatory Science

  • Life Science / Nephrology  / Chronic Kidney Disease, Hemodialysis, Peritoneal Dialysis, PD+HD

  • Life Science / Bacteriology  / Bacteriology

Research History (researchmap)

  • Niigata University Medical and Dental Hospital   Clinical and Translational Research Center   Associate Professor

    2021.4

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  • Pharmaceuticals and Medical Devices Agency   Office of New Drug I   Reviewer

    2017.4 - 2021.3

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    Country:Japan

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  • The University of Tokyo   Faculty of Medicine University Hospital Clinical Research Support Center the University of Tokyo Hospital   Specially Appointed Assistant Professor

    2015.8 - 2017.3

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    Country:Japan

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  • The University of Tokyo   Faculty of Medicine University Hospital Nephrology and Endocrinology   Clinical Fellow

    2015.4 - 2015.8

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    Country:Japan

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  • Mitsui Memorial Hospital   Division of Medicine   Clinical Fellow

    2008.10 - 2011.3

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    Country:Japan

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  • The University of Tokyo   Faculty of Medicine University Hospital Nephrology and Endocrinology   Senior resident

    2008.4 - 2008.9

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    Country:Japan

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  • Nagasaki Medical Center   Junior resident

    2006.4 - 2008.3

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    Country:Japan

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  • The University of Tokyo   Faculty of Medicine University Hospital Nephrology and Endocrinology   Postdoctoral fellow

    2019.4 - 2021.3

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    Country:Japan

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  • The University of Tokyo   Faculty of Medicine University Hospital Nephrology and Endocrinology   Postdoctoral fellow

    2017.4 - 2019.3

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    Country:Japan

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Research History

  • Niigata University   Clinical and Translational Research Center, University Medical and Dental Hospital   Associate Professor

    2021.4

Education

  • The University of Tokyo   Graduate School of Medicine

    2011.4 - 2015.3

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    Country: Japan

    Notes: Doctor course

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  • Saga University   Faculty of Medicine   School of Medicine

    2000.4 - 2006.3

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    Country: Japan

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Professional Memberships

  • International Society of Nephrology

    2022.8

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  • Japanese Society for Peritoneal Dialysis

    2021.12

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  • The Japanese Society of Clinical Pharmacology and Therapeutics

    2021.3

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  • The Japanese Society for Dialysis Therapy

    2006.6

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  • The Japanese Society of Nephrology

    2006.6

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  • The Japanese Society of Internal Medicine

    2006.4

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Committee Memberships

  • Pharmaceuticals and Medical Devices Agency   Scientific Adviser  

    2021.5   

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    Committee type:Government

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Qualification acquired

  • Doctor

 

Papers

  • Aortic arch calcification affects causes of death in patients on hemodialysis: a retrospective cohort study Reviewed International journal

    Toyohiro Hashiba, Mototsugu Tanaka, Tomoko Honda, Satoru Kishi, Yoshiyasu Ogura, Yuto Takenaka, Satoshi Furuse, Kyosuke Nishio, Kazunobu Masaki, Tatsuya Kano, Naobumi Mise

    Renal Replacement Therapy   8 ( 1 )   2022.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    <title>Abstract</title><sec>
    <title>Background</title>
    Aortic arch calcification (AAC) is a well-known risk factor for death in patients on hemodialysis (HD); however, the causes of death among them have not been well studied. The study aimed to investigate the distribution of causes of death and long-term prognosis among different degrees of AAC in HD patients.


    </sec><sec>
    <title>Methods</title>
    A retrospective cohort study was conducted on patients undergoing HD at two clinics in Japan. AAC grades 0 to 3 were categorized by chest radiograph at baseline, and mortality and causes of death were collected. A subgroup analysis was performed to evaluate the relationship between causes of death and age, diabetes mellitus, and dialysis vintage in each AAC grade.


    </sec><sec>
    <title>Results</title>
    A total of 321 patients were included in the analysis. During 5.2 ± 2.1 years, 117 patients died, and the death rates in AAC grades 0, 1, 2, and 3 were 19.3% (17/88), 35.2% (51/145), 46.3% (25/54), and 70.6% (24/34), respectively. The major causes of death were cardiovascular disease (CVD, 39.3%), infection (20.5%), and malignancy (15.4%) in the entire cohort. In AAC grade 3, CVD mortality (33.3%) remains as the most common cause of death, although death of infection (29.2%) and malnutrition (16.7%) increased markedly. A subgroup analysis showed that AAC grade 3 was mostly old, non-diabetic patients with a long dialysis vintage and was susceptible to death of infection or malnutrition.


    </sec><sec>
    <title>Conclusions</title>
    CVD was the most common cause of death among all AAC grades, although death of infection and malnutrition markedly increased in those with severe AAC. Attention should be paid to CVD, infection, and malnutrition in HD patients with severe AAC.


    </sec>

    File: Hashiba_et al_Cause of death AAC HD_RRT2022.pdf

    DOI: 10.1186/s41100-022-00394-8

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    Other Link: https://link.springer.com/article/10.1186/s41100-022-00394-8/fulltext.html

  • Effluent N‐terminal expressed in renal cell carcinoma/mesothelin predicts increased peritoneal permeability in patients undergoing peritoneal dialysis Reviewed International journal

    Mayumi Idei, Masaaki Abe, Mototsugu Tanaka, Junichiro Nakata, Miwa Isshiki, Okio Hino, Takashi Miida

    Therapeutic Apheresis and Dialysis   2022.1

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

    INTRODUCTION: We investigated whether N-terminal and C-terminal products of expressed in renal cell carcinoma/mesothelin (N-ERC and C-ERC) in peritoneal effluent can predict peritoneal permeability in patients undergoing peritoneal dialysis (PD). METHODS: Thirty-seven peritoneal effluent samples were obtained from 26 PD patients. High transport status was determined by the peritoneal equilibration test as a dialysate/plasma ratio of creatinine (D/P Cr) ≥ 0.81. Effluent cancer antigen 125 (CA125) was used as a reference. RESULTS: Effluent N-ERC concentration was better correlated with D/P Cr than effluent C-ERC or CA125 concentration. In multivariate analyses, effluent N-ERC and C-ERC, but not CA125, were significant predictors of high transport status after adjusting for age, PD duration, and residual renal Kt/V. ROC analysis showed that effluent N-ERC was the best predictor of high transport status among those three biomarkers. CONCLUSION: Effluent N-ERC predicts increased peritoneal permeability in patients undergoing PD.

    DOI: 10.1111/1744-9987.13786

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    Other Link: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1744-9987.13786

  • A bacterial small RNA regulates the adaptation of Helicobacter pylori to the host environment Reviewed International journal

    Ryo Kinoshita-Daitoku, Kotaro Kiga, Masatoshi Miyakoshi, Ryota Otsubo, Yoshitoshi Ogura, Takahito Sanada, Zhu Bo, Tuan Vo Phuoc, Tokuju Okano, Tamako Iida, Rui Yokomori, Eisuke Kuroda, Sayaka Hirukawa, Mototsugu Tanaka, Arpana Sood, Phawinee Subsomwong, Hiroshi Ashida, Tran Thanh Binh, Lam Tung Nguyen, Khien Vu Van, Dang Quy Dung Ho, Kenta Nakai, Toshihiko Suzuki, Yoshio Yamaoka, Tetsuya Hayashi, Hitomi Mimuro

    Nature Communications   12 ( 1 )   2021.12

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    <title>Abstract</title>Long-term infection of the stomach with <italic>Helicobacter pylori</italic> can cause gastric cancer. However, the mechanisms by which the bacteria adapt to the stomach environment are poorly understood. Here, we show that a small non-coding RNA of <italic>H. pylori</italic> (HPnc4160, also known as IsoB or NikS) regulates the pathogen’s adaptation to the host environment as well as bacterial oncoprotein production. In a rodent model of <italic>H. pylori</italic> infection, the genomes of bacteria isolated from the stomach possess an increased number of T-repeats upstream of the HPnc4160-coding region, and this leads to reduced HPnc4160 expression. We use RNA-seq and iTRAQ analyses to identify eight targets of HPnc4160, including genes encoding outer membrane proteins and oncoprotein CagA. Mutant strains with HPnc4160 deficiency display increased colonization ability of the mouse stomach, in comparison with the wild-type strain. Furthermore, HPnc4160 expression is lower in clinical isolates from gastric cancer patients than in isolates derived from non-cancer patients, while the expression of HPnc4160’s targets is higher in the isolates from gastric cancer patients. Therefore, the small RNA HPnc4160 regulates <italic>H. pylori</italic> adaptation to the host environment and, potentially, gastric carcinogenesis.

    File: Kinoshita et al_Small RNA regulates H.pylori adaptation_Nat Commun2021.pdf

    DOI: 10.1038/s41467-021-22317-7

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    Other Link: http://www.nature.com/articles/s41467-021-22317-7

  • The PMDA’s view on the limited pipeline of nephrology drugs in Japan Reviewed International journal

    Mototsugu Tanaka, Mutsuhiro Ikuma

    Kidney International   100 ( 1 )   241 - 242   2021.7

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    DOI: 10.1016/j.kint.2021.03.034

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  • The PMDA Perspectives on New Oral Prolyl Hydroxylase Domain Enzyme Inhibitors for Renal Anemia Reviewed International journal

    Mototsugu Tanaka, Mutsuhiro Ikuma, Wataru Asakura, Yasuhiro Fujiwara

    Clinical Pharmacology & Therapeutics   111 ( 2 )   358 - 361   2021.5

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1002/cpt.2275

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    Other Link: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cpt.2275

  • Achievements and challenges of the Sakigake designation system in Japan Reviewed International journal

    Mototsugu Tanaka, Mayumi Idei, Hiroshi Sakaguchi, Ryosuke Kato, Daisuke Sato, Kenji Sawanobori, Shuichi Kawarasaki, Toshiyuki Hata, Asako Yoshizaki, Miki Nakamura, Mutsuhiro Ikuma

    British Journal of Clinical Pharmacology   87 ( 10 )   4027 - 4035   2021.3

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    DOI: 10.1111/bcp.14807

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  • Association between age at disease onset of anti-neutrophil cytoplasmic antibody–associated vasculitis and clinical presentation and short-term outcomes Reviewed International journal

    Sara Monti, Anthea Craven, Catherine Klersy, Carlomaurizio Montecucco, Roberto Caporali, Richard Watts, Peter A Merkel, Raashid Luqmani, Katerina Achilleos, Matthew Adler, Marco A Alba, Marco A Alba, Daniel A Albert, Fatma Alibaz-Oner, Paul Allcoat, Koichi Amano, Manishka Amarasuriya, Naomi A Amudala, Jacqueline Andrews, Amy M Archer, Yoshihiro Arimura, Inoshi Atukorala, Elsa Azevedo, Shruti Bajad, Corisande Baldwin, Lillian J Barra, Bo Baslund, Neil Basu, Mahire Baykal, Christoph Berger, Ewa Berglin, Emilio Besada, Mamta Bhardwaj, Antje Bischof, Daniel Blockmans, Janet Blood, Juliana Bordignon Draibe, Sarah Brand, Mariana Brandao, Ian N Bruce, Amanda Butler, Leonard H Calabrese, Daniel Camprubi Ferrer, Simon Carette, Diana Carmona, Helga Ceunen, Kuntal Chakravarty, Peter T Chapman, Zdenka Chocova, Sharon A Chung, Weiping Ci, Maria C Cid, Tiffany M Clark, Michael R Clarkson, Felipe de Jesus Contreras-Rodríguez, Richard Conway, Kelly Cooke, Xavier Corbella Virós, Ana Cordeiro, Andreia Costa, Anthea Craven, Karen Culfear, Thomas Daikeler, Debashish Danda, Siddharth K Das, Bhaskar Dasgupta, Alice M De Castro, Natasha Dehghan, Roni Devassy, Navjot Dhindsa, Andreas P Diamantopoulos, Haner Direskeneli, Hiroaki Dobashi, Du Juan, Maumer Durrani, Clive Edelsten, Johanna Eifert, Sallie Elhayek, Sunhoury Elsideeg, Tomomi Endo, Abdulsamet Erden, Burak Erer, Per Eriksson, Zeynep Erturk, Georgina Espígol-Frigolé, Mara Felicetti, Alaistair Ferraro, José M Ferro, Aurore Fifi-Mah, Luis Felipe Flores-Suárez, Oliver Flossmann, Deirdre Flynn, João Eurico Fonseca, Jayne Foot, Michelle Foote, Lindsy Forbess, Shouichi Fujimoto, Kazuhito Fukuoka, Carolina Furtado, Shunsuke Furuta, Angelo L Gaffo, Phil Gallagher, Na Gao, Paul Gatenby, Nagui Gendi, Ruth Geraldes, Anneleen Gerits, Andrea Gioffredi, Luke Gomples, Maria João Gonçalves, Prisca Gondo, Anne Graham, Rebecca Grainger, David T Gray, Peter C Grayson, Laura Griffiths, Yanqiu Guo, Rajiva Gupta, Micael Gylling, Rula A Hajj-Ali, Nevin Hammam, Masayoshi Harigai, Lorraine Hartley, Janine Haslett, Alaa Hassan, Gulen Hatemi, Bernhard Hellmich, Liesbet Henckaerts, Joerg C Henes, Joanna Hepburn, Vera Herd, Christoph Hess, Catherine Hill, Andrea Hinojosa-Azaola, Junichi Hirahashi, Fumio Hirano, Alojzija Hočevar, Julia Holle, Nicole Hollinger, Sakae Homma, Theresa Howard, Rachel K Hoyles, Zdenka Hruskova, Gayle Hutcheon, Maria Ignacak, Annette Igney-Oertel, Kei Ikeda, Noriko Ikegaya, Samyukta Jagadeesh, Jane Jaquith, David R W Jayne, Teresa Jewell, Colin Jones, Abhay Joshi, Umut Kalyoncu, Sevil Kamalı, Sanjeet Kamath, Kan Sow Lai, Shinya Kaname, Suresh Kanchinadham, Ömer Karadağ, Miho Karube, Marek Kaszuba, Ramanjot Kaur, Tamihiro Kawakami, Soko Kawashima, Nader Khalidi, Asad Khan, Masao Kikuchi, Levent Kilic, Makiko Kimura, Maria J King, Sebastian Klapa, Rainer Klocke, Tatsuo Kobayashi, Shigeto Kobayashi, Yoshinori Komagata, Andreas Kronbichler, Pawel Kuczia, Mandal Santosh Kumar, Miho Kurosawa, Peter Lamprecht, Carol A Langford, Peter Lanyon, Catherine Laversuch, Sang Jin Lee, Simona Leoni, Jing Li, Kimberly Liang, Patrick Liang, Hua Liao, Lim Ai Lee, Raashid A Luqmani, Amanda Lyle, Matthew MacDonald, Sarah L Mackie, Leah Madden, Malgorzata Magliano, Hirofumi Makino, Ashima Makol, Ritu Malaiya, Anshuman Malaviya, Ramesh Manthri, Federica Maritati, Ana Martins da Silva, Justin C Mason, Cecilia Matara, Kazuo Matsui, Eric L Matteson, Dawn McBride, Keith McCullough, Lucy McGeoch, John McLaren, Caitlin McMillian, Naval Mendiratta, Ajit Menon, Dimos Merinopoulos, Peter A Merkel, Peter Merkel, Sandra Messier, Robert G Micheletti, Karen Mills, Nataliya Milman, Masahiro Minoda, Ranjana Walker Minz, Claudia Möck, Aladdin J Mohammad, Sergey Moiseev, Marta Moitinho, Eamonn Molloy, Paul A Monach, Marian Montgomery, Frank Moosig, Manoosh Moradizadeh, Matthew Morgan, Ann W Morgan, Ann-Marie Morgan, Alice Muir, Chetan Mukhtyar, Antje Müller, Francesco Muratore, Eri Muso, Ritambhra Nada, Hiroshi Nakajima, Toshiki Nakajima, Hiroto Nakano, Anupapama Nandagudi, Thomas Neumann, Ying Fun Ng, Kooi Heng Ng, Estela L Nogueira, Nilesh Nolkha, Dan Nordström, Pavel Novikov, Asanka Nugaliyadde, John L O’Donnell, Jennifer O’Donoghue, Lorraine O’Neill, Edmond O’Riordan, Margaret Oatley, Koshu Okubo, Elena Oliva, Hideto Oshikawa, Yuichiro Ota, Roberto Padoan, Christian Pagnoux, Lili Pan, Kalliopi Panaritis, Jin Kyun Park, Sanjeev Patel, Pravin Patil, Giulia Pazzola, Adrian Peall, Fiona Pearce, Seval Pehlevan, Liliana Pereira, Tom Pettersson, Christian A Pineau, Laura Pirilä, Bartlomiej Poglodek, Cristina Ponte, Sergio Prieto-González, Sangeetha R Priya, Bally Purewal, Silke Purschke, Jukka Putaala, Stefanie Quickert, Vicki Quincey, Subhra Raghuvanshi, Liza Rajasekhar, Dwarakanathan Ranganathan, Manish Rathi, David Rees, Frances Rees, Ulrike Renken, Giovanna Restuccia, Rennie L Rhee, Brian Rice, Diane Robins, Joanna Robson, Joanna Robson, Miguel Rodrigues, Vasco C Romão, Žiga Rotar, Carlee Ruediger, Abraham Rutgers, Ana C Sá, Maria João Saavedra, Ken-ei Sada, Ilfita Sahbudin, Carlo Salvarani, Namneet Sandhu, Ernestina Santos, Yuji Sato, Valentin S Schäfer, Franco Schiavon, Wolfgang A Schmidt, Mårten Segelmark, Amira Shahin, Aman Sharma, Julie Shotton, Cristiana Silva, Ora Gewurz Singer, Goutham Sivasuthan, Susan Smolen, Xavier Solanich-Moreno, Laura Soldevila Boixader, Yeong Wook Song, Jason Springer, Antoine G Sreih, Antoine G Sreih, Ragini Srivastava, Lisa K Stamp, Robert Stevens, Daniel Strbian, Keishi Sugino, Cord Sunderkötter, Ravi Suppiah, Katsuya Suzuki, Kazuo Suzuki, Zoltán Szekanecz, Jan Sznajd, Kirsi Taimen, Paul P Tak, Tsutomu Takeuchi, Naoho Takizawa, Lilian Tames, Bee Eng Tan, Mototsugu Tanaka, Man Wai Tang, Turgut Tatlisumak, Vladimir Tesar, Alan Thomas, Xinping Tian, Kenichiro Tokunaga, Enrico Tombetti, Matija Tomšič, Bahtiyar Toz, Tatsuo Tsukamoto, Shunya Uchida, Ali Ugur Unal, Maria L Urban, Joichi Usui, Augusto Vaglio, Srinivasan Venkatachalam, Erin Vermaak, Vishad Viswanath, Takashi Wada, Shrikant Wagh, Daniel J Wallace, Giles Walters, Bastian Walz, Jin Wan, Tian Wang, Guochun Wang, Kenneth J Warrington, Richard A Watts, Katarzyna Wawrzycka-Adamczyk, Praveen Weeratunga, Michael H Weisman, Sugeesha Wickramasinghe, Mark Williams, Megan Williams, Krzysztof Wojcik, Laticia Woodruff, Theodoros Xenitidis, Hidehiro Yamada, Kunihiro Yamagata, Chee-Seng Yee, Myeongjae Yoon, Kazuki Yoshida, Hajime Yoshifuji, Steven R Ytterberg, Wako Yumura, Hania Zayed, Xiaofeng Zeng, Ming-Hui Zhao, Anna Zugaj, Joanna Zuk

    Rheumatology   60 ( 2 )   617 - 628   2021.2

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:Oxford University Press (OUP)  

    <title>Abstract</title>
    <sec>
    <title>Objectives</title>
    ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- and older-onset patients are still incompletely understood.


    </sec>
    <sec>
    <title>Methods</title>
    We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: &amp;lt;65 years or ≥65 years. We adjusted associations for the type of AAV and the type of ANCA (anti-MPO, anti-PR3 or negative).


    </sec>
    <sec>
    <title>Results</title>
    A total of 1338 patients with AAV were included: 66% had disease onset at &amp;lt;65 years of age [female 50%; mean age 48.4 years (s.d. 12.6)] and 34% had disease onset at ≥65 years [female 54%; mean age 73.6 years (s.d. 6)]. ANCA (MPO) positivity was more frequent in the older group (48% vs 27%; P = 0.001). Younger patients had higher rates of musculoskeletal, cutaneous and ENT manifestations compared with older patients. Systemic, neurologic,cardiovascular involvement and worsening renal function were more frequent in the older-onset group. Damage accrual, measured with the Vasculitis Damage Index (VDI), was significantly higher in older patients, 12% of whom had a 6 month VDI ≥5, compared with 7% of younger patients (P = 0.01). Older age was an independent risk factor for early death within 6 months from diagnosis [hazard ratio 2.06 (95% CI 1.07, 3.97); P = 0.03].


    </sec>
    <sec>
    <title>Conclusion</title>
    Within 6 months of diagnosis of AAV, patients &amp;gt;65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients.


    </sec>

    File: Monti et al_DCVAS_Rheumatology2021.pdf

    DOI: 10.1093/rheumatology/keaa215

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  • Ultrafiltration volume by once‐weekly hemodialysis is a predictor of technique survival of combination therapy with peritoneal dialysis and hemodialysis Reviewed International journal

    Mototsugu Tanaka, Yoshitaka Ishibashi, Yoshifumi Hamasaki, Yuka Kamijo, Mayumi Idei, Takahiro Nishi, Michio Takeda, Hiroshi Nonaka, Masaomi Nangaku, Naobumi Mise

    Therapeutic Apheresis and Dialysis   2021.2

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    Overhydration is a major cause of technique failure of peritoneal dialysis (PD). Hence, we investigated the impact of ultrafiltration (UF) volume by once-weekly hemodialysis (HD), excess volume beyond their dry weight, on technique survival of PD and HD combination therapy (PD+HD). Forty-six anuric PD+HD patients were divided into three groups according to baseline UF volume by HD: low-UF (<mean - 1SD), middle-UF (≥mean - 1SD and <mean + 1SD), and high-UF (≥mean + 1SD). High-UF group showed larger extracellular water normalized to height (P = .038) and longer HD sessions (P < .001) compared with low-UF group, whereas low-UF group was older than middle-UF group (P = .001). Technique survival rate was significantly lower in high-UF group than in low and middle-UF groups (P < .001), and the rates at 44 months were 80%, 90%, 20% in low, middle, and high-UF groups, respectively. Chronic overhydration was the leading cause of technique failure for all. This study suggests that fluid overload remains a major cause of technique failure of PD even after once-weekly HD is added.

    DOI: 10.1111/1744-9987.13509

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    Other Link: https://onlinelibrary.wiley.com/doi/full-xml/10.1111/1744-9987.13509

  • Rationales of delay and difference in regulatory review by Japan, the USA and Europe among new drugs first approved in Japan Reviewed International journal

    Mototsugu Tanaka, Mayumi Idei, Hiroshi Sakaguchi, Ryosuke Kato, Daisuke Sato, Kenji Sawanobori, Shuichi Kawarasaki, Toshiyuki Hata, Asako Yoshizaki, Miki Nakamura, Mutsuhiro Ikuma

    British Journal of Clinical Pharmacology   87 ( 8 )   3279 - 3291   2021.1

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    DOI: 10.1111/bcp.14749

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  • Need for evidence on long-term prognosis of PD+HD: a commentary Reviewed International journal

    Mototsugu Tanaka, Naobumi Mise

    BMC Nephrology   22 ( 1 )   2021.1

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    Authorship:Lead author, Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Springer Science and Business Media LLC  

    <title>Abstract</title>Combination therapy with peritoneal dialysis and hemodialysis (PD+HD) is an alternative dialysis method for patients with end-stage kidney disease (ESKD). The complementary use of once-weekly HD expedites to achieve adequate dialysis and enables to prolong PD duration. Although PD+HD has been widely employed among Japanese PD patients, it is much less common outside Japan. Clinical evidences are still not enough, especially in long-term prognosis and appropriate treatment duration, suitable patients, and generalizability. A retrospective cohort study by Chung et al. (BMC Nephrol 21:348, 2020) compared the risk of mortality and hospitalization between PD patients who were transferred to PD+HD and those who were transferred to HD in Taiwan. Because the mortality and hospitalization rates did not differ between the groups, the authors concluded that, PD+HD may be a rational and cost-effective treatment option. It should be noted that the effects of PD+HD on long-term prognosis are still unknown due to too-short PD+HD duration. However, the study identified the high-risk patient population and showed the generalizability of PD+HD. PD+HD is a treatment of choice in patients with ESKD who prefer PD lifestyles even after decline in residual kidney function.

    File: Tanaka and Mise_ commentary_BMC Nephrol2021.pdf

    DOI: 10.1186/s12882-020-02212-x

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    Other Link: http://link.springer.com/article/10.1186/s12882-020-02212-x/fulltext.html

  • Evolving Landscape of New Drug Approval in Japan and Lags from International Birth Dates: Retrospective Regulatory Analysis Reviewed International journal

    Mototsugu Tanaka, Mayumi Idei, Hiroshi Sakaguchi, Ryosuke Kato, Daisuke Sato, Kenji Sawanobori, Shuichi Kawarasaki, Toshiyuki Hata, Asako Yoshizaki, Miki Nakamura, Mutsuhiro Ikuma

    Clinical Pharmacology & Therapeutics   2020.11

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    The Pharmaceuticals and Medical Devices Agency (PMDA) have approved hundreds of new drugs in recent years. We retrospectively analyzed the new drugs approved in Japan from 2008 to 2019, and identify the first-in-world approvals and clarify the current drug lag. The new drug and the drug lag were defined as a drug with a new active substance and a difference between the approval date in Japan and the international birth date, respectively. Among 400 new drugs approved in Japan during the last 12 years, 80 (20.0%) were first approved in Japan, and 320 were outside Japan (the United States: 202, 50.5%; Europe: 82, 20.5%; other regions: 36, 9.0%). Of these, 45 new drugs have not yet been approved outside Japan, and the remaining 355 have been globally approved in Japan and overseas. The number of new drug approvals were the largest in oncology followed by metabolic/endocrine and infectious diseases. The median drug lags (year) among all 400 new drugs and 355 new drugs with global approvals were 4.3 and 4.7 in the 1st tertile (2008-2011), 1.5 and 2.6 in the 2nd tertile (2012-2015), and reduced to 1.3 and 2.2 in the 3rd tertile (2016-2019), respectively. Substantial drug lag remains in neurology, psychiatry, and therapeutic areas where the number of new drug approvals was relatively small. Collectively, one-fifth of the new drugs approved in Japan are first-in-world approvals. Drug lag has been greatly decreased, although it still exists.

    File: Tanaka et al_400NAS_Clin Pharmacol Ther2020.pdf

    DOI: 10.1002/cpt.2080

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  • International consensus definitions of clinical trial outcomes for kidney failure: 2020 Reviewed International journal

    Adeera Levin, Rajiv Agarwal, William G. Herrington, Hiddo L. Heerspink, Johannes F.E. Mann, Shahnaz Shahinfar, Katherine R. Tuttle, Jo-Ann Donner, Vivekanand Jha, Masaomi Nangaku, Dick de Zeeuw, Meg J. Jardine, Kenneth W. Mahaffey, Aliza M. Thompson, Mary Beaucage, Kate Chong, Glenda V. Roberts, Duane Sunwold, Hans Vorster, Madeleine Warren, Sandrine Damster, Charu Malik, Vlado Perkovic, Shuchi Anand, Nicholas Argent, Elena Babak, Debasish Banerjee, Jonathan Barratt, Aminu K. Bello, Angelito A. Bernardo, Jaime Blais, William Canovatchel, Fergus J. Caskey, Josef Coresh, Ian H. de Boer, Kai-Uwe Eckardt, Rhys DR. Evans, Harold I. Feldman, Agnes B. Fogo, Hrefna Gudmundsdottir, Takayuki Hamano, David C.H. Harris, Sibylle J. Hauske, Richard Haynes, Charles A. Herzog, Thomas Hiemstra, Thomas Idorn, Lesley Inker, Julie H. Ishida, David W. Johnson, Charlotte Jones-Burton, Amer Joseph, Audrey Koitka-Weber, Matthias Kretzler, Robert Lawatscheck, Adrian Liew, Louise Moist, Saraladevi Naicker, Reiko Nakashima, Uptal Patel, Roberto Pecoits Filho, Jennifer B. Rose, Noah L. Rosenberg, Marvin Sinsakul, William E. Smoyer, Laura Sola, Amy R. Sood, Benedicte Stengel, Maarten W. Taal, Mototsugu Tanaka, Marcello Tonelli, Allison Tong, Robert Toto, Michele Trask, Ifeoma I. Ulasi, Christoph Wanner, David C. Wheeler, Benjamin O. Wolthers, Harold M. Wright, Yoshihisa Yamada, Elena Zakharova

    Kidney International   98 ( 4 )   849 - 859   2020.10

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    Kidney failure is an important outcome for patients, clinicians, researchers, healthcare systems, payers, and regulators. However, no harmonized international consensus definitions of kidney failure and key surrogates of progression to kidney failure exist specifically for clinical trials. The International Society of Nephrology convened an international multi-stakeholder meeting to develop consensus on this topic. A core group, experienced in design, conduct, and outcome adjudication of clinical trials, developed a database of 64 randomized trials and the 163 included definitions relevant to kidney failure. Using an iterative process, a set of proposed consensus definitions were developed and subsequently vetted by the larger multi-stakeholder group of 83 participants representing 18 different countries. The consensus of the meeting participants was that clinical trial kidney failure outcomes should be comprised of a composite that includes receipt of a kidney transplant, initiation of maintenance dialysis, and death from kidney failure; it may also include outcomes based solely on laboratory measurements of glomerular filtration rate: a sustained low glomerular filtration rate and a sustained percent decline in glomerular filtration rate. Discussion included important considerations, such as (i) recognition of existing nomenclature for kidney failure; (ii) applicability across resource settings; (iii) ease of understanding for all stakeholders; and (iv) avoidance of inappropriate complexity so that the definitions can be used across ranges of populations and trial methodologies. The final definitions reflect the consensus for use in clinical trials.

    File: Kidney failure clinical trial outcome definitions_A Levin et al_KI2020.pdf

    DOI: 10.1016/j.kint.2020.07.013

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  • Role of Roxadustat for ESA-Resistant Renal Anemia? —Read with Caution Reviewed International journal

    Mototsugu Tanaka, Kayo Shinohara, Akiko Ono, Mutsuhiro Ikuma

    Journal of the American Society of Nephrology   31 ( 11 )   ASN.2020060821 - ASN.2020060821   2020.9

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    File: Tanaka M, et al_Role of Roxadustat for ESA-Resistant Renal Anemia —Read with Caution_letter_JASN2020.pdf

    DOI: 10.1681/asn.2020060821

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  • Bioimpedance Spectroscopy‐Based Fluid Status in Combined Dialysis Compared With Hemodialysis and Peritoneal Dialysis: A Cross‐Sectional Study Reviewed International journal

    Mototsugu Tanaka, Yoshitaka Ishibashi, Yoshifumi Hamasaki, Yuka Kamijo, Mayumi Idei, Takahiro Nishi, Michio Takeda, Hiroshi Nonaka, Masaomi Nangaku, Naobumi Mise

    Therapeutic Apheresis and Dialysis   24 ( 4 )   373 - 379   2020.8

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    Combination therapy with peritoneal dialysis and hemodialysis (PD+HD) is widely used in Japan for PD patients with decreased residual renal function. However, fluid status in PD+HD patients has not been well studied. In this cross-sectional study, we compared fluid status in 41 PD+HD patients with that in 103 HD and 92 PD patients using the bioimpedance spectroscopy. Extracellular water normalized to patient height (NECW, kg/m) was the highest in pre-HD (8.3 ± 1.6) followed by PD (7.9 ± 2.7), PD+HD (7.5 ± 2.5), and post-HD patients (6.9 ± 1.5) (P < 0.01). By multiple linear regression analysis, PD+HD was associated with a significantly lower NECW than pre-HD (β = -0.8, P = 0.03) and similar to PD (β = -0.5, P = 0.24) and post-HD (β = 0.6, P = 0.08) after adjustment for age, sex, diabetic nephropathy, ischemic heart disease, dialysis period, and daily urine volume. There was no correlation between NECW and daily urine volume in all dialysis groups. Average daily fluid removal (a sum of urine volume and ultrafiltration volume by dialysis) was positively correlated with NECW in PD+HD and pre-HD, but not in PD and post-HD patients. Our results suggest that fluid status in PD+HD patients with decreased residual renal function is acceptable as compared with that in HD and PD patients.

    DOI: 10.1111/1744-9987.13444

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  • Mutational diversity in mutY deficient Helicobacter pylori and its effect on adaptation to the gastric environment Reviewed International journal

    Ryo Kinoshita-Daitoku, Kotaro Kiga, Takahito Sanada, Yoshitoshi Ogura, Zhu Bo, Tamako Iida, Rui Yokomori, Eisuke Kuroda, Mototsugu Tanaka, Arpana Sood, Toshihiko Suzuki, Kenta Nakai, Tetsuya Hayashi, Hitomi Mimuro

    Biochemical and Biophysical Research Communications   525 ( 3 )   806 - 811   2020.5

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    Helicobacter pylori, a pathogenic bacterium that colonizes in the human stomach, harbors DNA repair genes to counter the gastric environment during chronic infection. In addition, H. pylori adapts to the host environment by undergoing antigenic phase variation caused by genomic mutations. The emergence of mutations in nucleotide sequences is one of the major factors underlying drug resistance and genetic diversity in bacteria. However, it is not clear how DNA repair genes contribute to driving the genetic change of H. pylori during chronic infection. To elucidate the physiological roles of DNA repair genes, we generated DNA repair-deficient strains of H. pylori (ΔuvrA, ΔuvrB, ΔruvA, Δnth, ΔmutY, ΔmutS, and Δung). We performed susceptibility testing to rifampicin in vitro and found that ΔmutY exhibited the highest mutation frequency among the mutants. The number of bacteria colonizing the stomach was significantly lower with ΔmutY strain compared with wild-type strains in a Mongolian gerbil model of H. pylori infection. Furthermore, we performed a genomic sequence analysis of the strains isolated from the Mongolian gerbil stomachs eight weeks after infection. We found that the isolated ΔmutY strains exhibited a high frequency of spontaneous G:C to T:A mutations. However, the frequency of phase variations in the ΔmutY strain was almost similar to the wild-type strain. These results suggest that MutY may play a role in modes of gastric environmental adaptation distinct from phase variation.

    DOI: 10.1016/j.bbrc.2020.02.087

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  • Hospitalization for Patients on Combination Therapy With Peritoneal Dialysis and Hemodialysis Compared With Hemodialysis Reviewed International journal

    Mototsugu Tanaka, Yoshitaka Ishibashi, Yoshifumi Hamasaki, Yuka Kamijo, Mayumi Idei, Takuya Kawahara, Takahiro Nishi, Michio Takeda, Hiroshi Nonaka, Masaomi Nangaku, Naobumi Mise

    Kidney International Reports   5 ( 4 )   468 - 474   2020.4

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    Introduction: Combination therapy with peritoneal dialysis and hemodialysis (PD+HD) is widely used for PD patients with decreased residual kidney function in Japan; however, hospitalization for this combined dialysis has not been investigated so far. We compared the risk of hospitalization for PD+HD with that for HD.
    Methods: A multicenter, prospective observational study was conducted on 42 PD+HD and 42 HD patients matched for age and diabetic nephropathy. The main outcome measure was the cumulative incidence of hospitalization for any cause assessed with the Kaplan-Meier method. Hospitalization rates (the number of admissions per 100 patient-years) associated with dialysis modality were also calculated. The impact of dialysis modality on time to hospitalization was analyzed using the Cox proportional hazard model.
    Results: There was no significant difference between groups in terms of age, sex, dialysis vintage, diabetic nephropathy, and comorbidities. The cumulative incidence of hospitalization did not significantly differ between the groups (log-rank test, P = 0.36). Although total hospitalization rates were 66.0 in PD+HD and 59.2 in HD, hospitalization rates for the sum of PD-related infections (a composite of catheter-related infection and peritonitis) and vascular access troubles were 21.7 in PD+HD and 7.2 in HD. On univariate Cox proportional hazard analysis, dialysis modality had no significant impact on time to hospitalization.
    Conclusion: The risk of hospitalization was not significantly different between PD+HD and HD, although PD+HD patients had a higher risk of dialysis access-related complications than HD patients.

    File: Tanaka M, et al. Hospitalization for PD+HD Versus HD_KI rep2020.pdf

    DOI: 10.1016/j.ekir.2020.01.004

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  • Group A Streptococcus establishes pharynx infection by degrading the deoxyribonucleic acid of neutrophil extracellular traps Reviewed International journal

    Mototsugu Tanaka, Ryo Kinoshita-Daitoku, Kotaro Kiga, Takahito Sanada, Bo Zhu, Tokuju Okano, Chihiro Aikawa, Tamako Iida, Yoshitoshi Ogura, Tetsuya Hayashi, Koshu Okubo, Miho Kurosawa, Junichi Hirahashi, Toshihiko Suzuki, Ichiro Nakagawa, Masaomi Nangaku, Hitomi Mimuro

    Scientific Reports   10 ( 1 )   3251 - 3251   2020.2

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    Group A Streptococcus (GAS) secretes deoxyribonucleases and evades neutrophil extracellular killing by degrading neutrophil extracellular traps (NETs). However, limited information is currently available on the interaction between GAS and NETs in the pathogenicity of GAS pharyngitis. In this study, we modified a mouse model of GAS pharyngitis and revealed an essential role for DNase in this model. After intranasal infection, the nasal mucosa was markedly damaged near the nasal cavity, at which GAS was surrounded by neutrophils. When neutrophils were depleted from mice, GAS colonization and damage to the nasal mucosa were significantly decreased. Furthermore, mice infected with deoxyribonuclease knockout GAS mutants (∆spd, ∆endA, and ∆sdaD2) survived significantly better than those infected with wild-type GAS. In addition, the supernatants of digested NETs enhanced GAS-induced cell death in vitro. Collectively, these results indicate that NET degradation products may contribute to the establishment of pharyngeal infection caused by GAS.

    File: Tanaka M, et al. GAS_SciRep2020.pdf

    DOI: 10.1038/s41598-020-60306-w

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  • Health-related quality of life on combination therapy with peritoneal dialysis and hemodialysis in comparison with hemodialysis and peritoneal dialysis: A cross-sectional study Reviewed International journal

    Mototsugu Tanaka, Yoshitaka Ishibashi, Yoshifumi Hamasaki, Yuka Kamijo, Mayumi Idei, Takuya Kawahara, Takahiro Nishi, Michio Takeda, Hiroshi Nonaka, Masaomi Nangaku, Naobumi Mise

    Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis   40 ( 5 )   462 - 469   2020.1

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    Background: The health-related quality of life (HRQOL) of dialysis patients has not been well examined, especially in combination therapy with peritoneal dialysis and hemodialysis (PD+HD) patients. We compared the HRQOL of PD+HD patients with that of HD and PD patients.
    Methods: A multicenter, cross-sectional study was conducted on 36 PD+HD, 103 HD, and 90 PD patients in Japan who completed the Kidney Disease Quality of Life Short Form 36, version 1.3. HRQOL scores were summarized into physical- (PCS), mental- (MCS), role/social- (RCS), and kidney disease component summaries (KDCS).
    Results: Of the PD+HD patients, 31 (86%) transferred from PD and 5 (14%) transferred from HD. They had the longest dialysis vintage and the smallest urine volume. PCS, MCS, and KDCS HRQOL scores of PD+HD patients were comparable with those of HD and PD patients. However, the RCS score for PD+HD was significantly higher than that for HD (p = 0.020) and comparable with that for PD. PD+HD and PD were associated with significantly higher RCS scores than HD after adjusting for age, gender, diabetic nephropathy, dialysis vintage, ischemic heart disease, and peripheral arterial disease.
    Conclusions: For RCS, HRQOL in PD+HD patients was better than that in HD and comparable with that in PD patients, whereas the PCS, MCS, and KDCS HRQOL scores of PD+HD patients were comparable with those of HD and PD patients.

    DOI: 10.1177/0896860819894066

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  • ESA Resistance May Be a Potential Confounder for Mortality among Different ESA Types Reviewed International journal

    Mototsugu Tanaka, Kayo Shinohara, Akiko Ono, Mutsuhiro Ikuma

    Journal of the American Society of Nephrology   30 ( 9 )   1772.1 - 1772   2019.9

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    File: Tanaka M, et al_ESA resistance may be a potential confounder for mortality among different ESA types_JASN2020.pdf

    DOI: 10.1681/asn.2019060556

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  • A multicenter, randomized controlled trial comparing the identification rate of stigmata of recent hemorrhage and rebleeding rate between early and elective colonoscopy in outpatient-onset acute lower gastrointestinal bleeding: study protocol for a randomized controlled trial Reviewed International journal

    Ryota Niikura, Naoyoshi Nagata, Atsuo Yamada, Hisashi Doyama, Yasutoshi Shiratori, Tsutomu Nishida, Shu Kiyotoki, Tomoyuki Yada, Tomoki Fujita, Tetsuya Sumiyoshi, Kenkei Hasatani, Tatsuya Mikami, Tetsuro Honda, Katsuhiro Mabe, Kazuo Hara, Katsumi Yamamoto, Mariko Takeda, Munenori Takata, Mototsugu Tanaka, Tomohiro Shinozaki, Mitsuhiro Fujishiro, Kazuhiko Koike

    Trials   19 ( 1 )   214 - 214   2018.12

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    Background: The clinical benefit of early colonoscopy within 24 h of arrival in patients with severe acute lower gastrointestinal bleeding (ALGIB) remains controversial. This trial will compare early colonoscopy (performed within 24 h) versus elective colonoscopy (performed between 24 and 96 h) to examine the identification rate of stigmata of recent hemorrhage (SRH) in ALGIB patients. We hypothesize that, compared with elective colonoscopy, early colonoscopy increases the identification of SRH and subsequently improves clinical outcomes.
    Methods: This trial is an investigator-initiated, multicenter, randomized, open-label, parallel-group trial examining the superiority of early colonoscopy over elective colonoscopy (standard therapy) in ALGIB patients. The primary outcome measure is the identification of SRH. Secondary outcomes include 30-day rebleeding, success of endoscopic treatment, need for additional endoscopic examination, need for interventional radiology, need for surgery, need for transfusion during hospitalization, length of stay, 30-day thrombotic events, 30-day mortality, preparation-related adverse events, and colonoscopy-related adverse events. The sample size will enable detection of a 9% SRH rate in elective colonoscopy patients and a SRH rate of ≥ 26% in early colonoscopy patients with a risk of type I error of 5% and a power of 80%.
    Discussion: This trial will provide high-quality data on the benefits and risks of early colonoscopy in ALGIB patients.

    File: Niikura R, Tanaka M, et al. Trials2018.pdf

    DOI: 10.1186/s13063-018-2558-y

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  • 初回前立腺針生検陰性例に対するナフトピジルによる前立腺がん発生頻度の低下効果に関する前向き無作為化比較研究 Reviewed

    山田 大介, 松島 常, 榎本 裕, 村田 高史, 牧野 克洋, 立川 隆光, 中野 敏彦, 阿部 真樹, 塩澤 廸夫, 東 剛司, 粕谷 豊, 鈴木 基文, 佐藤 ゆずり, 西松 寛明, 石川 晃, 角谷 成紀, 岡根谷 利一, 永本 将一, 山田 雄太, 中川 徹, 宮嵜 英世, 加藤 温, 橿淵 啓史, 近藤 靖司, 久米 春喜, 井川 靖彦, 藤村 哲也, 内藤 晶裕, 田中 基嗣, 高田 宗典, 上村 夕香理, 宮川 仁平, 森川 鉄平, 福原 浩, 本間 之夫

    日本泌尿器科学会総会   106回   PP2 - 068   2018.4

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  • A prospective randomized controlled study on the Suppression of Prostate Cancer by Naftopidil (SNAP) Reviewed International journal

    Daisuke Yamada, Haruki Kume, Hideyo Miyazaki, Mototsugu Tanaka, Munenori Takata, Yukari Uemura, Teppei Morikawa, Yutaka Enomoto, Motofumi Suzuki, Hiroaki Nishimatsu, Tohru Nakagawa, Tetsuya Fujimura, Hiroshi Fukuhara, Yasuhiko Igawa, Yukio Homma

    Preventive Medicine and Community Health   1 ( 1 )   2018

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    File: Yamada D, Tanaka M, et al. Naftpidil protocol_Prev Med Commun Health2018.pdf

    DOI: 10.15761/pmch.1000106

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  • Bioequivalence study of BEPOTASTINE BESILATE OD TABLETS 10 mg (NICHIIKO) on healthy adults Reviewed

    Chie Sakanaka, Shinya Ishii, Keiko Ueda, Yumi Kameyama, Akiko Kishi, Kenji Kirihara, Kazushi Suzuki, Munenori Takata, Mototsugu Tanaka, Chikako Wada, Makoto Ito, Yuriko Nishimura

    Medical Consultation & New Remedies   55 ( 2 )   91 - 99   2018

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  • Age-Related Differences of Organism-Specific Peritonitis Rates: A Single-Center Experience Reviewed International journal

    Nagaaki Kotera, Mototsugu Tanaka, Mari Aoe, Masatomo Chikamori, Tomoko Honda, Ayako Ikenouchi, Rika Miura, Mai Sugahara, Satoshi Furuse, Katsunori Saito, Naobumi Mise

    Therapeutic Apheresis and Dialysis   20 ( 6 )   655 - 660   2016.12

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    Peritonitis remains an important cause of morbidity and mortality in peritoneal dialysis (PD) patients, but its incidence and the distribution of causative organisms vary widely between institutions and age groups. This study was performed to investigate the recent status and risk factors of PD-related peritonitis and to clarify differences between age groups. We retrospectively reviewed the medical records of 119 PD patients treated at our department between January 2002 and January 2013. We calculated both overall and organism-specific peritonitis rates and also analyzed risk factors. Sixty-three episodes of peritonitis occurred during 261.5 patient-years for an incident rate of 0.24 episodes/patient-year. Multivariate analysis showed that older age (≥65 years) and hypoalbuminemia (<3.0 g/dL) were associated with an increased risk of peritonitis (P = 0.035 and P = 0.029, respectively). In elderly patients (≥65 years old), the rate of peritonitis due to Gram-positive and Gram-negative bacteria was 0.17 and 0.08 episodes/patient-year, respectively, and Gram-positive peritonitis was markedly more frequent than in younger patients (<65 years old). In particular, there was a high frequency of Staphylococcus aureus peritonitis in elderly patients (0.09 episodes/patient-year) and it had a poor outcome. At our department, the risk of peritonitis was increased in older patients and patients with hypoalbuminemia. The distribution of causative organisms was markedly different between age groups and analysis of organism-specific peritonitis rates helped to identify current problems with our PD program.

    DOI: 10.1111/1744-9987.12449

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  • Lactoferrin Suppresses Neutrophil Extracellular Traps Release in Inflammation

    Koshu Okubo, Mako Kamiya, Yasuteru Urano, Hiroshi Nishi, Jan M. Herter, Tanya Mayadas, Daigoro Hirohama, Kazuo Suzuki, Hiroshi Kawakami, Mototsugu Tanaka, Miho Kurosawa, Shinji Kagaya, Keiichi Hishikawa, Masaomi Nangaku, Toshiro Fujita, Matsuhiko Hayashi, Junichi Hirahashi

    EBioMedicine   10   204 - 215   2016.8

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    DOI: 10.1016/j.ebiom.2016.07.012

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  • Immunomodulation with eicosapentaenoic acid supports the treatment of autoimmune small-vessel vasculitis Reviewed International journal

    Junichi Hirahashi, Kimito Kawahata, Makoto Arita, Ryo Iwamoto, Keiichi Hishikawa, Mie Honda, Yoshifumi Hamasaki, Mototsugu Tanaka, Koshu Okubo, Miho Kurosawa, Osamu Takase, Masanori Nakakuki, Kan Saiga, Kazuo Suzuki, Shoji Kawachi, Akihiro Tojo, George Seki, Takeshi Marumo, Matsuhiko Hayashi, Toshiro Fujita

    Scientific Reports   4 ( 1 )   2015.5

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    Small-vessel vasculitis is a life-threatening autoimmune disease that is frequently associated with anti-neutrophil cytoplasmic antibodies (ANCAs). Conventional immunotherapy including steroids and cyclophosphamide can cause serious adverse events, limiting the efficacy and safety of treatment. Eicosapentaenoic acid (EPA), a key component of fish oil, is an omega-3 polyunsaturated fatty acid widely known to be cardioprotective and beneficial for vascular function. We report two elderly patients with systemic ANCA-associated vasculitis (AAV) in whom the administration of EPA in concert with steroids safely induced and maintained remission, without the use of additioal immunosuppressants. To explore the mechanisms by which EPA enhances the treatment of AAV, we employed SCG/Kj mice as a spontaneous murine model of AAV. Dietary enrichment with EPA significantly delayed the onset of crescentic glomerulonephritis and prolonged the overall survival. EPA-derived anti-inflammatory lipid mediators and their precursors were present in the kidney, plasma, spleen, and lungs in the EPA-treated mice. Furthermore, a decrease in ANCA production and CD4/CD8-double negative T cells, and an increase in Foxp3(+) regulatory T cells in the lymph nodes of the kidney were observed in the EPA-treated mice. These clinical and experimental observations suggest that EPA can safely support and augment conventional therapy for treating autoimmune small-vessel vasculitis.

    File: Hirahashi J, Tanaka M, et al. EPA for small-vessel vasculitis. Sci Rep2014.pdf

    DOI: 10.1038/srep06406

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  • Dialysis Amyloid Deposition in the Aortic Valve and Its Association with Aortic Stenosis Reviewed International journal

    Noriaki Kurita, Akiko Fujii, Nagaaki Kotera, Mototsugu Tanaka, Shinji Tanaka, Takeshi Miyairi, Tokuichiro Sugimoto, Masaya Mori, Shunichi Fukuhara, Naobumi Mise

    Blood Purification   40 ( 2 )   146 - 154   2015

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    Background: The relationship between dialysis amyloid (DA) deposition in the aortic valve (AV) and aortic stenosis (AS) is unknown.
    Methods: This was a cross-sectional study. AV specimens of dialysis patients (median vintage: 8.8 years) consecutively collected from cardiac surgeries (n = 56) or autopsies (n = 13) were examined by a board-certified pathologist blinded to clinical data. DAs were considered to be present if deposits were stained both by Congo red with apple-green birefringence under polarized light and by anti-β2-microblobulin antibody. Degree of deposition was graded as follows: Amyloid (-), no deposit; Amyloid (1+), occasional small deposits; Amyloid (2+), multiple small to large deposits or a single large deposit. Calcification was defined as a calcified deposit with a diameter >1 mm in the specimen. Severe AS (sAS) was defined as a mean gradient >50 mm Hg by echocardiogram. We examined the proportion of DAs and the association between DAs and the sAS.
    Results: DAs were present in 71% (n = 49) of specimens and primarily co-localized with calcification. Non-dialysis related amyloid was found in one specimen. After excluding this specimen, sAS was associated with ‘Amyloid (1+) and Calcification >1 mm' and ‘Amyloid (2+) and Calcification >1 mm' (vs. ‘Amyloid (-) and Calcification ≤1 mm', odds ratios (ORs): 13.5 and 34.2, respectively). Furthermore, after adjustment for covariates, sAS was found to be associated with ‘Amyloid (2+) and Calcification >1 mm' (OR: 24.3).
    Conclusions: DA deposition in the AV was prevalent among dialysis patients. DA deposition with accompanying calcification might contribute to the severity of AS.

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  • Increased peritoneal permeability at peritoneal dialysis initiation is a potential cardiovascular risk in patients using biocompatible peritoneal dialysis solution Reviewed International journal

    Yoshifumi Hamasaki, Kent Doi, Mototsugu Tanaka, Haruki Kume, Yoshitaka Ishibashi, Yutaka Enomoto, Toshiro Fujita, Yukio Homma, Masaomi Nangaku, Eisei Noiri

    BMC Nephrology   15 ( 1 )   173 - 173   2014.12

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    Background: Cardiovascular disease is a frequent cause of death in peritoneal dialysis patients. Biocompatible peritoneal dialysis solutions with neutral pH have been anticipated to reduce cardiovascular disease more than conventional peritoneal dialysis solutions with low pH, but it remains unclear which factors at peritoneal dialysis initiation increase cardiovascular risk in patients using biocompatible peritoneal dialysis solutions. This study was undertaken to investigate which clinical factors at peritoneal dialysis initiation, including peritoneal transport status, are associated with cardiovascular event in patients using biocompatible peritoneal dialysis solution.
    Methods: This retrospective cohort study of peritoneal dialysis patients using biocompatible solutions with neutral pH assessed relations of clinical parameters at peritoneal dialysis initiation to cardiovascular event during the subsequent five years.
    Results: Of 102 patients who started peritoneal dialysis, cardiovascular event occurred in 18. Age, history of cardiovascular disease before peritoneal dialysis initiation, hemoglobin, serum albumin, C-reactive protein, peritoneal permeability defined by the ratio of dialysate to plasma creatinine concentration at 4 hr (D/Pcre) in peritoneal equilibration test (PET), number of patients in each PET category defined by D/Pcre, and peritoneal protein clearance significantly differed between patients with and without cardiovascular event. For patients divided according to PET category using Kaplan-Meier method, the group of high average to high peritoneal transporters exhibited significantly high incidence of cardiovascular event and mortality compared with the groups of low and low-average peritoneal transporters (Log rank; p=0.0003 and 0.005, respectively). A Cox proportional hazards model showed independent association of PET category classification with cardiovascular event.
    Conclusions: Peritoneal permeability expressed as PET category at peritoneal dialysis initiation is an independent cardiovascular risk factor in peritoneal dialysis patients using biocompatible peritoneal dialysis solution with neutral pH. Greater peritoneal permeability at peritoneal dialysis initiation might reflect subclinical vascular disorders.

    File: Hamasaki Y, Tanaka M, et al. CV risk and peritoneal permeability BMC Nephrol2014.pdf

    DOI: 10.1186/1471-2369-15-173

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  • Successful Treatment of Acute Kidney Injury in Patients with Idiopathic Nephrotic Syndrome Using Human Atrial Natriuretic Peptide Reviewed International journal

    Kohei Ueda, Junichi Hirahashi, George Seki, Mototsugu Tanaka, Natsuki Kushida, Yusuke Takeshima, Yoshitaka Nishikawa, Toshiro Fujita, Masaomi Nangaku

    Internal Medicine   53 ( 8 )   865 - 869   2014

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    The acute onset of idiopathic nephrotic syndrome (NS) is often accompanied by acute kidney injury, which can lead to congestive heart failure and lung edema. In this report, we present two cases of NS-induced acute kidney injury successfully treated with a low dose of carperitide, a human atrial natriuretic peptide. In combination with standard diuretic therapy and immunotherapy, carperitide retained the renal function and spared the need for renal replacement therapy, including hemodialysis. Although further investigation in clinical trials is required to validate these findings, carperitide may be useful for maintaining the renal function in cases of NS-induced acute kidney injury.

    DOI: 10.2169/internalmedicine.53.1724

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  • Peritoneal Dialysis Combined with Extracorporeal Ultrafiltration in Refractory Heart Failure: A Case Report Reviewed International journal

    Yu Ishimoto, Naobumi Mise, Mototsugu Tanaka, Mai Sugahara, Takafumi Kanemitsu, Masafumi Kobayashi, Lisa Uchida, Nagaaki Kotera, Shinji Tanaka, Tokuichiro Sugimoto

    Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis   33 ( 5 )   582 - 583   2013.9

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    DOI: 10.3747/pdi.2012.00212

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  • AA amyloid nephropathy with predominant vascular deposition in Crohn's disease Reviewed International journal

    Noriaki Kurita, Nagaaki Kotera, Yu Ishimoto, Mototsugu Tanaka, Shinji Tanaka, Nobuo Toda, Akiko Fujii, Kiyonori Kobayashi, Tokuichiro Sugimoto, Naobumi Mise

    Clinical Nephrology   79 ( 03 )   229 - 232   2013.3

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    A 44-year-old man with a 17-year history of Crohn's disease (CD) was referred to our nephrology department on suspicion of drug-induced nephrotoxicity. Over the preceding 18 months, he had slowly progressive renal insufficiency with slight urinary abnormalities. His disease activity had been well controlled up to that point with 5-aminosalicylic acid and azathiopurine. Laboratory examination revealed slight proteinuria without hematuria and an elevated serum creatinine level of 1.4 mg/dl. Pathological examination revealed amyloid A (AA) deposition in the kidney, predominantly in the arterial and arteriolar walls with little to none in the glomerular capillaries. AA amyloidosis is typically accompanied by glomerular amyloid deposition and massive proteinuria. In the present case, however, vascular amyloid deposition was predominant, and the renal function was deteriorated with slight urinary abnormalities. The present case confirmed the importance of conducting a definitive pathological diagnosis of renal insufficiency in CD patients.

    DOI: 10.5414/cn107151

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  • Acute Kidney Injury after a Pelvic Surgery Reviewed International journal

    Mototsugu Tanaka, Junichi Hirahashi, Takamoto Ohse, Toshiro Fujita

    Nephrology   18 ( 1 )   73 - 74   2013.1

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    DOI: 10.1111/j.1440-1797.2012.01609.x

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  • Successful Long-Term Peritoneal Dialysis in Combination with Once-Weekly Hemodialysis: A Case Report Reviewed International journal

    Naobumi Mise, Shinji Tanaka, Lisa Uchida, Yu Ishimoto, Nagaaki Kotera, Mototsugu Tanaka, Tokuichiro Sugimoto

    Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis   32 ( 5 )   572 - 573   2012.9

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    DOI: 10.3747/pdi.2011.00301

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  • Peritoneal Dialysis With Takayasu Arteritis: A Report of Three Cases Reviewed International journal

    Mototsugu Tanaka, Yoshitaka Ishibashi, Junichi Hirahashi, Toshiro Fujita

    Therapeutic Apheresis and Dialysis   16 ( 2 )   198 - 199   2012.4

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    DOI: 10.1111/j.1744-9987.2011.01041.x

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  • Glomerular capillary light chain thrombi in multiple myeloma Reviewed International journal

    Noriaki Kurita, Mototsugu Tanaka, Shinji Tanaka, Akiko Fujii, Tokuichiro Sugimoto, Yutaka Yamaguchi, Naobumi Mise

    Kidney International   80 ( 12 )   1378 - 1378   2011.12

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    File: Kurita N, Tanaka M, et al. Glomerular light chain in Myeloma case. KI2011.pdf

    DOI: 10.1038/ki.2011.342

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  • Acute systemic hypotension after arteriovenous fistula construction in a patient with severe aortic stenosis Reviewed International journal

    Naobumi Mise, Lisa Uchida, Mototsugu Tanaka, Shinji Tanaka, Hiroyoshi Nakajima, Tokuichiro Sugimoto

    Clinical and Experimental Nephrology   15 ( 5 )   788 - 790   2011.10

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    We report the case of a 53-year-old hemodialysis patient with severe aortic stenosis, who developed acute systemic hypoperfusion after arteriovenous fistula (AVF) construction. He presented with hypotension and repeated syncope soon after distal radiocephalic AVF construction, and finally developed a respiratory arrest. His blood pressure and hemodynamics recovered promptly by sub-emergent aortic valve replacement surgery. In the present case, the heart with severe aortic stenosis could not increase cardiac output in response to the reduction in peripheral vascular resistance caused by the AVF. High-output heart failure, a relatively rare AVF-associated disorder, occurs with an excessive AVF flow, usually more than 3 L/min or 30% of cardiac output. However, heart failure may develop soon after construction of an AVF with a moderate blood flow if a patient's cardiac function is severely impaired. In addition, heart failure may improve with AVF preservation if the underlying heart disease is treatable.

    DOI: 10.1007/s10157-011-0484-3

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  • Effects of Combination Therapy with Peritoneal Dialysis and Hemodialysis on Left Ventricular Hypertrophy Reviewed International journal

    Mototsugu Tanaka, Naobumi Mise, Hiroyoshi Nakajima, Lisa Uchida, Yu Ishimoto, Nagaaki Kotera, Shinji Tanaka, Noriaki Kurita, Tokuichiro Sugimoto

    Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis   31 ( 5 )   598 - 600   2011.9

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    DOI: 10.3747/pdi.2010.00273

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  • sitagliptin内服開始後に急性腎不全を呈した一例

    佐藤 信彦, 八木 喬, 田中 基嗣, 平橋 淳一, 大瀬 貴元, 山田 秀臣, 関 常司, 藤田 敏郎

    日本腎臓学会誌   53 ( 6 )   916 - 916   2011.8

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  • 高安動脈炎による重症心血管合併症を有する末期腎不全患者に対して腹膜透析が有用であった3例

    田中 基嗣, 石橋 由孝, 平橋 淳一, 佐藤 信彦, 片桐 大輔, 高良 洋平, 関 常司, 藤田 敏郎

    日本腎臓学会誌   53 ( 6 )   920 - 920   2011.8

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  • Case report: IgG4-related hypophysitis presenting with secondary adrenal insufficiency and central diabetes insipidus in a type 1 diabetes patient. Reviewed

    Kotera N, Isogawa A, Uchida L, Ishimoto Y, Tanaka M, Tanaka S, Kishi S, Kurita N, Mise N, Sugimoto T

    Nihon Naika Gakkai zasshi   100 ( 4 )   1044 - 1047   2011.4

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    DOI: 10.2169/naika.100.1044

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  • Arteriovenous Access Closure in Hemodialysis Patients With Refractory Heart Failure: A Single Center Experience Reviewed International journal

    Noriaki Kurita, Naobumi Mise, Shinji Tanaka, Mototsugu Tanaka, Keiko Sai, Takahiro Nishi, Sumio Miura, Ikutaro Kigawa, Takeshi Miyairi, Tokuichiro Sugimoto

    Therapeutic Apheresis and Dialysis   15 ( 2 )   195 - 202   2011.4

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    Arteriovenous dialysis access may impose a burden on the cardiac system. The objective of this study is to examine the usefulness of access closure in hemodialysis patients with refractory heart failure and to identify possible factors associated with symptomatic improvements. The study population comprised 33 hemodialysis patients with symptomatic heart failure (New York Heart Association [NYHA] class ≥ II), who underwent arteriovenous access closure (30 fistulas and three grafts) between 1991 and 2008. In all patients, heart failure was refractory to all possible medical and surgical treatments, and persisted after optimal dry weight control. First, short-term changes in hemodynamics, clinical symptoms and echocardiographic morphology were examined. Second, clinical and echocardiographic parameters were compared between responders (N=23), who demonstrated NYHA class improvement after access closure, and non-responders (N=10). After access closure, systolic blood pressure rose and the heart rate decreased significantly. Body weight and echocardiographic parameters did not change significantly. Twenty-three patients (70%) demonstrated NYHA class improvement and were designated as responders. In responders, the duration from access creation to closure was significantly shorter and fewer had ischemic heart disease, compared with non-responders. Access flow, cardiac output and ejection fraction were comparable between the two groups. Although the five-year survival was 20.2% in all patients, responders showed better early survival than non-responders. Arteriovenous access closure improved clinical symptoms in 70% of patients with refractory heart failure. This improvement was especially likely to be achieved in patients without ischemic heart disease and those who developed heart failure within a relatively short time after access creation.

    DOI: 10.1111/j.1744-9987.2010.00907.x

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  • Case of mesangial proliferative glomerulonephritis complicated with multicentric Castleman's disease. Reviewed

    Mototsugu Tanaka

    Nihon Jinzo Gakkai shi   53 ( 2 )   189 - 194   2011.1

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    We report a case of a 47-year-old man with multicentric Castleman's disease (MCD) and progressive renal dysfunction due to mesangial proliferative glomerulonephritis, possibly from IgA nephropathy. At age 36 years, he was referred to a hematologist due to hypergammaglobulinemia. Because of systemic lymph node swelling, he underwent right cervical lymph node biopsy at age 41 years and MCD (plasma cell type)was diagnosed. During this period, microscopic hematuria and persistent proteinuria occurred and his renal function deteriorated (serum creatinine (Cr) rising from 0.7 mg/dL to 1.4 mg/dL). Treatment with intravenous methylprednisolone at the dose of 1 g daily for 3 days followed by oral prednisolone at 20 mg daily reduced his lymphadenopathy and improved the renal function. However, his renal function deteriorated again, from Cr 0.8 mg/dL to 1.8 mg/dL over 6 years in line with gradual prednisolone tapering to 6 mg daily. At age 47 years, he was referred to our nephrology department and underwent a renal biopsy. The microscopic examination showed IgA nephropathy with crescent formation, accompanied by mild lymphoplasmacytic tubulointerstitial nephritis. Treatment with the same dose of intravenous methylprednisolone therapy followed by oral prednisolone at 40 mg daily, improved his proteinuria, hematuria and renal dysfunction. The coexistence of MCD and IgA nephropathy is a rare phenomenon. In addition, IL-6, overproduced by MCD might have influenced the mesangial cell proliferation and the activity of IgA nephropathy in the present case.

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  • Aberrantly Glycosylated IgA1 as a Factor in the Pathogenesis of IgA Nephropathy Invited Reviewed International journal

    Mototsugu Tanaka, George Seki, Tomonosuke Someya, Michio Nagata, Toshiro Fujita

    Clinical and Developmental Immunology   2011   1 - 7   2011

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    Predominant or codominant immunoglobulin (Ig) A deposition in the glomerular mesangium characterizes IgA nephropathy (IgAN). Accumulated glomerular IgA is limited to the IgA1 subclass and usually galactose-deficient. This underglycosylated IgA may play an important role in the pathogenesis of IgAN. Recently, antibodies against galactose-deficient IgA1 were found to be well associated with the development of IgAN. Several therapeutic strategies based on corticosteroids or other immunosuppressive agents have been shown to at least partially suppress the progression of IgAN. On the other hand, several case reports of kidney transplantation or acquired IgA deficiency uncovered a remarkable ability of human kidney to remove mesangial IgA deposition, resulting in the long-term stabilization of kidney function. Continuous exposure to circulating immune complexes containing aberrantly glycosylated IgA1 and sequential immune response seems to be essential in the disease progression of IgAN. Removal of mesangial IgA deposition may be a challenging, but fundamental approach in the treatment of IgAN.

    File: Tanaka M, Seki G, et al. IgAN Review. ClinDevImmunol2011.pdf

    DOI: 10.1155/2011/470803

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  • Neisseria subflava peritonitis in a type1 diabetes patient on peritoneal dialysis. Reviewed

    Nagaaki Kotera, Naobumi Mise, Lisa Uchida, Yu Ishimoto, Mototsugu Tanaka, Shinji Tanaka, Noriaki Kurita, Tokuichiro Sugimoto

    J Jpn Soc Dial Ther   44 ( 4 )   319 - 322   2011

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    A 34-year-old male with end-stage renal failure due to type1 diabetes started peritoneal dialysis (PD) via a double-cuffed Tenckhoff catheter in April 2008. He was using a double-bag system with manual connectology and underwent nocturnal intermittent PD. In January 2009, he developed his first episode of peritonitis, presenting with slight fever, abdominal pain, diarrhea, vomiting and cloudy dialysate. Physical examination demonstrated abdominal rebound tenderness. Drained dialysate was cloudy with an elevated cell count of 2,500/μL (96% polymorphonuclear leukocytes). He was admitted to the hospital and successfully treated with 8 days of intraperitoneal or intravenous cefazolin and ceftazidime, followed by oral cefotiam for 6 days. There was no recurrence of peritonitis thereafter. Neisseria subflava was isolated from the dialysate and was identified as the pathogen causing peritonitis. <I>Neisseria subflava</I> is commensal in the upper respiratory tract, but may rarely cause infections, such as endocarditis and meningitis. A few cases of <I>Neisseria peritonitis</I> have been reported in PD patients, even in those without concomitant diseases. In the present case, contamination by a droplet from the mouth was considered the most probable cause of peritonitis, because the patient did not wear a mask during bag exchanges. The importance of wearing a mask for infection control during PD bag exchanges was reconfirmed.

    DOI: 10.4009/jsdt.44.319

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  • Resolution of Henoch-Schönlein purpura nephritis after acquired IgA deficiency Reviewed International journal

    Mototsugu Tanaka, George Seki, Kenichi Ishizawa, Junichi Hirahashi, Kenichiro Miura, Takashi Sekine, Tomonosuke Someya, Hiroshi Hataya, Michio Nagata, Toshiro Fujita

    Pediatric Nephrology   25 ( 11 )   2355 - 2358   2010.11

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    We report a case of Henoch-Schönlein purpura nephritis (HSPN) with acquired IgA deficiency due to parvovirus B19 infection. The patient was diagnosed as having Henoch-Schönlein purpura (HSP) at 6 years old, and subsequently developed macrohematuria and massive proteinuria of 7.4 g/day with decreased creatinine clearance of 70.2 ml/min/1.73 m(2) and significantly elevated serum IgA level of 449 mg/dl. The first kidney biopsy yielded the diagnosis of severe HSPN. After the initiation of the immunosuppressive therapy, the patient was infected with parvovirus B19 and developed virus-associated hemophagocytic syndrome (VAHS). Thereafter, the serum level of IgA selectively decreased and remained undetectable until the present time. Repeated kidney biopsies performed over a period of 14 years revealed a remarkable histological improvement in association with stabilization of the patient's kidney function. Considering the severity of initial kidney injury, persistent acquired IgA deficiency was likely to add favorable effects to the immunosuppressive therapy in this patient with HSPN.

    DOI: 10.1007/s00467-010-1568-0

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  • A Case of Churg-Strauss Syndrome With Necrotizing Crescentic Glomerulonephritis Accompanied by Acute Coronary Syndrome Due to Vasospasm Reviewed International journal

    Mototsugu Tanaka, Naobumi Mise, Noriaki Kurita, Takeshi Suzuki, Kazuhiro Hara, Akiko Fujii, Noriko Uesugi, Tokuichiro Sugimoto

    American Journal of Kidney Diseases   56 ( 2 )   e5 - e9   2010.8

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    We report a case of Churg-Strauss syndrome coexistent with coronary vasospasm and pauci-immune necrotizing crescentic glomerulonephritis. A 54-year-old man with bronchial asthma and allergic rhinitis was admitted to our hospital because of acute coronary syndrome. Angiography showed diffuse coronary artery spasm without anatomic stenosis. Acute coronary syndrome due to vasospasm was diagnosed. However, subsequent administration of vasodilators did not suppress angina symptoms. In addition, marked eosinophilia, eosinophilic pneumonitis, chronic sinusitis, pericardial effusion, and slight hematuria with red blood cell casts were detected. Although kidney function was normal, a kidney biopsy showed necrotizing crescentic glomerulonephritis with eosinophilic infiltration in both glomeruli and interstitium. With the diagnosis of Churg-Strauss syndrome, oral prednisolone at a dose of 60 mg/d was administered. Cardiac symptoms, pulmonary and sinonasal lesions, pericardial effusion, and urine sediment resolved rapidly. Six months later, a repeated kidney biopsy showed remarkable improvement and no eosinophilic infiltration. Coronary vasospasm with eosinophilia might be refractory to vasodilators and sensitive to corticosteroid therapy and often has been related to Churg-Strauss syndrome. Slight abnormalities in urine sediment can be the clue to the diagnosis of severe kidney involvement of Churg-Strauss syndrome.

    DOI: 10.1053/j.ajkd.2010.03.011

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  • MEFV mutations in Japanese rheumatoid arthritis patients. Reviewed International journal

    Kiyoshi Migita, Tadashi Nakamura, Yumi Maeda, Taichiro Miyashita, Tomohiro Koga, Mototsugu Tanaka, Minoru Nakamura, Atsumasa Komori, Hiromi Ishibashi, Tomoki Origuchi, Hiroaki Ida, Eiji Kawasaki, Michio Yasunami, Katsumi Eguchi

    Clinical and experimental rheumatology   26 ( 6 )   1091 - 1094   2008.11

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    Objective: Familiar Mediterranean Fever (FMF) is common among Mediterranean populations, while other populations are rarely affected. The aim of this study was to assess the involvement of MEFV gene mutations among Japanese rheumatoid arthritis patients with or without amyloid A (AA) amyloidosis.

    Methods: The frequency of the MEFV mutations, which were identified in Japanese FMF patients, was determined in 126 Japanese RA patients and 76 Japanese healthy subjects.

    Results: The M694I mutation was not observed among RA patients and healthy subjects. Allele frequency of R408Q, P369S, E148Q, L110P mutations account respectively for 3.3%, 3.9%, 23.7%, 9.2% in healthy subjects and 5.6%, 6.7%, 24.2%, 9.5% in RA patients. The overall mutation rate was comparable between the RA patients and healthy subjects, as well as between the RA patients with and without amyloidosis.

    Conclusion: This study shows the high prevalence of mutations of the MEFV genes in Japanese RA patients. However, our data suggest that the MEFV gene mutations may not be a genetic factor affecting the susceptibility of RA or the development of amyloidosis in a Japanese population.

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  • Acute hepatitis in a patient with familial Mediterranean fever Reviewed International journal

    Kiyoshi Migita, Seigo Abiru, Mototsugu Tanaka, Masahiro Ito, Taichiro Miyashita, Yumi Maeda, Tomohiro Koga, Minoru Nakamura, Atsumasa Komori, Hiroshi Yatsuhashi, Hiroaki Ida, Katsumi Eguchi, Kenji Hirayama, Michio Yasunami, Hiromi Ishibashi

    Liver International   28 ( 1 )   140 - 142   2007.10

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    Familial Mediterranean fever (FMF) is a hereditary syndrome characterized by recurrent episodes of fever and serositis. In this report, we describe a Japanese patient with FMF and Sjögren's syndrome, in whom acute elevations of transaminase occurred. The histological findings from the liver biopsy specimens demonstrated a nonspecific hepatitis, with liver cell necrosis and interlobular inflammatory cell invasion, without the presence of interface hepatitis or bile duct injury. This case underscores the possibility that MEFV mutations contribute to hepatic inflammation, as seen in this case, by way of an alteration of the pyrin function.

    DOI: 10.1111/j.1478-3231.2007.01598.x

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  • A Case of Churg-Strauss Syndrome with EBV Reactivation During the Course of Corticosteroid Therapy Reviewed

    Kyushu Journal of Rheumatology   27   56 - 62   2007.9

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  • Coexistence of familial Mediterranean fever and Sjögren's syndrome in a Japanese patient. Reviewed International journal

    Mototsugu Tanaka, Kiyoshi Migita, Taichiro Miyashita, Yumi Maeda, Minoru Nakamura, Atsumasa Komori, Hiromi Ishibashi, Katsumi Eguchi, Mihoko Kikuchi, Kenji Hirayama, Michio Yasunami

    Clinical and experimental rheumatology   25 ( 5 )   792   2007.9

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  • 腹膜透析ハンドブック

    石橋, 由孝, 衣笠, 哲史, 田中, 基嗣, 塚本, 真貴

    中外医学社  2012.9  ( ISBN:9784498124905

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  • 慢性腎臓病の臨床研究の批判的吟味

    田中基嗣( Role: Contributor)

    Medical Practice 39巻6号  2022.6 

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  • 保存期慢性腎臓病治療薬の薬事承認について

    田中基嗣( Role: Contributor)

    週刊日本医事新報 5065号  2021.5 

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  • 腹膜透析・腎移植ハンドブック

    石橋, 由孝, 衣笠, 哲史( Role: Contributor ,  PD+HD併用療法)

    中外医学社  2018.10  ( ISBN:9784498224421

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    Total pages:xi, 339p   Language:Japanese

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  • 現場で役立つ腎臓内科ポケットブック

    三瀬, 直文, 石橋, 由孝( Role: Contributor ,  浮腫・体液過剰のみかた)

    文光堂  2018.3  ( ISBN:9784830620461

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    Total pages:xiv, 252p   Language:Japanese

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  • 臨牀と研究

    ( Role: Contributor ,  生化学検査―腎機能の評価)

    大道学館出版部  2013.7 

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  • 血管炎 : 基礎と臨床のクロストーク

    ( Role: Contributor ,  ANCA関連血管炎における好中球と血管内皮障害)

    日本臨牀社  2013.2 

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  • 内科レジデント実践マニュアル : 経時的流れに応じた適切な治療

    田川, 一海, 杉本, 徳一郎, 三井記念病院( Role: Contributor)

    文光堂  2012.3  ( ISBN:9784830620263

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    Total pages:x, 468p   Language:Japanese

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  • スタンダード透析療法

    腎と透析, 編集委員会( Role: Contributor ,  高齢者への透析治療)

    東京医学社  2011.6 

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  • 透析患者の合併症50 : 患者さんにもわかりやすいシートでらくらく説明できる! : 基礎知識からナースのケアまでまるわかり!

    大平, 整爾( Role: Contributor ,  高血圧;不整脈)

    メディカ出版  2010.12  ( ISBN:9784840431231

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    Total pages:249p   Language:Japanese

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  • 透析療法事典

    中本, 雅彦, 佐中, 孜, 秋沢, 忠男( Role: Contributor ,  糖尿病透析患者の脳血管障害)

    医学書院  2009.6  ( ISBN:9784260008457

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    Total pages:31, 560p   Language:Japanese

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  • 初回前立腺針生検陰性例に対するナフトピジルによる前立腺がん発生頻度の低下効果に関する前向き無作為化比較研究

    山田 大介, 松島 常, 榎本 裕, 村田 高史, 牧野 克洋, 立川 隆光, 中野 敏彦, 阿部 真樹, 塩澤 廸夫, 東 剛司, 粕谷 豊, 鈴木 基文, 佐藤 ゆずり, 西松 寛明, 石川 晃, 角谷 成紀, 岡根谷 利一, 永本 将一, 山田 雄太, 中川 徹, 宮嵜 英世, 加藤 温, 橿淵 啓史, 近藤 靖司, 久米 春喜, 井川 靖彦, 藤村 哲也, 内藤 晶裕, 田中 基嗣, 高田 宗典, 上村 夕香理, 宮川 仁平, 森川 鉄平, 福原 浩, 本間 之夫

    日本泌尿器科学会総会   106回   PP2 - 068   2018.4

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  • ベポタスチンベシル酸塩OD錠10mg「日医工」の健康成人における生物学的同等性試験

    坂中 千恵, 石井 伸弥, 上田 恵子, 亀山 祐美, 岸 暁子, 切原 賢治, 鈴木 一詩, 高田 宗典, 田中 基嗣, 和田 千賀子, 伊藤 誠, 西村 優理子

    診療と新薬   55 ( 2 )   91 - 99   2018.2

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    健康成人男性を対象に、ベポタスチンベシル酸塩OD錠10mg「日医工」(試験製剤)と先発医薬品タリオンOD錠10mg(標準製剤)の生物学的同等性試験を行った。対象は水なし投与試験24例(20〜38歳、平均年齢26.2±5.9歳:体重50.5〜74.4kg、平均体重61.3±5.3kg)、水あり投与試験24例(22〜40歳、平均年齢30.1±6.0歳:体重53.1〜76.0kg、平均体重62.5±7.1kg)に分けて検討した。検討内容は、血漿中濃度推移、生物学的同等性、安全性とした。その結果、2剤における水なし投与、水あり投与のいずれの試験も同等性試験ガイドラインの判定基準を満たしていた。また、試験製剤による重篤な副作用は認めなかった。以上より、試験製剤は標準製剤と生物学的に同等で安全であると考えられた。

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  • 腹膜透析患者の尿中L-FABPと残存腎機能低下速度

    近森正智, 菅谷健, 矢野正生, 土屋綾子, 本田智子, 三浦理加, 菅原真衣, 金光剛史, 小林昌史, 池森(上條)敦子, 木村健二郎, 小寺永章, 内田梨沙, 田中基嗣, 田中真司, 石本遊, 石澤健一, 栗田宜明, 杉本徳一郎, 三瀬直文

    日本透析医学会雑誌   47 ( Supplement 1 )   2014

  • 生化学検査 腎機能の評価 (特集 臨床検査値をどう読むか)

    田中 基嗣, 平橋 淳一, 南学 正臣

    臨牀と研究   90 ( 7 )   895 - 901   2013.7

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    Language:Japanese   Publisher:大道学館出版部  

    CiNii Article

    CiNii Books

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    Other Link: http://search.jamas.or.jp/link/ui/2013304960

  • DIALYSIS AMYLOID DEPOSITION IN THE AORTIC VALVE AND THE ASSOCIATION WITH SEVERE AORTIC STENOSIS

    Noriaki Kurita, Akiko Fujii, Nagaaki Kotera, Mototsugu Tanaka, Shinji Tanaka, Takeshi Miyairi, Tokuichiro Sugimoto, Masaya Mori, Shunichi Fukuhara, Naobumi Mise

    NEPHROLOGY DIALYSIS TRANSPLANTATION   28   40 - 40   2013.5

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    Web of Science

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  • 【血圧と体液・電解質異常】 経皮的腎動脈形成術(PTRA)により治療抵抗性心不全・高血圧が改善した動脈硬化性腎動脈狭窄症の1症例

    矢作 和之, 三瀬 直文, 石本 遊, 小寺 永章, 田中 真司, 田中 基嗣, 栗田 宜明, 原 和弘, 杉本 徳一郎

    臨床体液   37   55 - 58   2010.8

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    Language:Japanese   Publisher:臨床体液研究会  

    62歳男。虚血性心疾患(3枝病変)に対し冠動脈バイパス術を施行後、経皮的冠動脈形成術を2回施行した。血漿レニン活性(PRA)、血漿アルドステロン(PAC)が高値で、二次性高血圧を疑われていた。気管支炎を契機に心不全が増悪し緊急入院となった。BNPは著明高値で、心陰影拡大と肺うっ血を認めた。心工コーでは左室収縮能が低下していた。軽度腎機能障害と低K血症とともに、PRAとPACが高値であったため、腎動脈狭窄症を疑った。腎動脈造影にて左腎動脈入口部に99%狭窄病変を確認した。血管造影上70%以上狭窄を有し、進行性、治療抵抗性高血圧症を呈しているため、経皮的腎動脈形成術(PTRA)を施行した。PTRA後、収縮期血圧は110mmHgまで下降し、低K血症、心磯能ともに改善、BNPは低下し、心不全症状も軽快した。

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  • 虚血性腸炎による腹膜炎(開腹手術やカテーテル抜去を断念し保存的に観察したPDラストの1剖検例)

    中塚拓馬, 三瀬直文, 石本遊, 小寺永章, 田中真司, 田中基嗣, 栗田宜明, 田川一海, 杉本徳一郎

    腎と透析   69   2010

  • 多発性骨髄腫に合併した管内増殖性糸球体腎炎の1例

    田中 基嗣, 正路 久美, 衣笠 哲史, 和田 健彦, 宇於崎 宏, 藤乗 嗣泰, 関 常司, 藤田 敏郎

    日本腎臓学会誌   51 ( 6 )   667 - 667   2009.8

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  • 【血液透析処方をどのように選択するか】 慢性合併症対策からみた透析処方 循環障害

    杉本 徳一郎, 三瀬 直文, 栗田 宜明, 田中 真司, 田中 基嗣

    臨床透析   25 ( 5 )   605 - 610   2009.5

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    Language:Japanese   Publisher:(株)日本メディカルセンター  

    血液透析が循環に及ぼす影響の二つの側面は,一つは動静脈を短絡するバスキュラー・アクセス(VA)が心機能に及ぼす影響であり,もう一つは除水を中心とする透析処置そのものである.VAの作製と修復に関しては,患者の心機能に応じて,内シャントやシャントグラフトの選択の是非を判断する必要がある.時に,シャント血流の遮断とVAの変更を考慮する必要がある.心機能障害のある患者で,丸2日蓄積した体液量を4時間で除去する治療が安全であるためには,食事管理の正確性が求められる.基礎疾患の治療など心機能保持の治療とともに,透析方法の評価と選択,通院の介助などの考慮が必要である.(著者抄録)

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  • RA患者におけるMEFV遺伝子の検討

    右田 清志, 田中 基嗣, 宮下 賜一郎, 古賀 智裕, 中村 稔, 中村 正, 井田 弘明, 江口 勝美

    日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集   51回・16回   408 - 408   2007.4

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Awards

  • Niigata University Outstanding Paper Award 2022

    2022.11  

    Mototsugu Tanaka

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Research Projects

  • Current status and issues of drug lag in Japan

    Grant number:21K18094  2021.4 - 2026.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Early-Career Scientists  Grant-in-Aid for Early-Career Scientists

    Mototsugu Tanaka

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    Authorship:Principal investigator 

    Grant amount:\4680000 ( Direct Cost: \3600000 、 Indirect Cost:\1080000 )

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  • Investigation of neutrophil extracellular trap degradation products using a new model of Streptococcus pyogenes tonsillitis.

    Grant number:17K14974  2017.4 - 2021.3

    Mototsugu Tanaka

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    Authorship:Principal investigator 

    Grant amount:\4290000 ( Direct Cost: \3300000 、 Indirect Cost:\990000 )

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  • Identification and functional analysis of neutrophil extracellular traps degradation product in Streptococcus pyogenes infections.

    Grant number:15H06158  2015.8 - 2017.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity start-up  Grant-in-Aid for Research Activity start-up

    Mototsugu Tanaka

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    Authorship:Principal investigator 

    Grant amount:\2990000 ( Direct Cost: \2300000 、 Indirect Cost:\690000 )

    We analyzed the whole-genome sequences of Streptococcus pyogenes that was used in our preliminary experiments. Based on bioinformatics analysis, we identified 3 genes coding DNases (SdaD2, endA, spd) and novel 2 DNA regions coding 5'-nucleotidase that potentially degrade neutrophil extracellular traps (NETs) to yield NETs degradation product (NETDP). We have succeeded to generate deletion mutants of 4 genes of them. The DNase activity analysis showed that the strains still possessed substantial DNase activities. We also investigated the effect of the residual bacteria in the assay system prepared from supernatants of NETs co-cultivated with bacteria. Now we are trying to establish deletion mutants of dual or triple genes of the targets to analyze the effect of NETDP production.

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  • Causes and measures for delayed orphan drug development

    Grant number:22K12894  2022.4 - 2026.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)  Grant-in-Aid for Scientific Research (C)

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    Grant amount:\4160000 ( Direct Cost: \3200000 、 Indirect Cost:\960000 )

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Media Coverage

  • Asia-Pacific Roundup: PMDA puts patients at heart of push for Japan-first approvals Newspaper, magazine

    Regulatory Affairs Professionals Society  Regulatory Focus  https://www.raps.org/news-and-articles/news-articles/2020/12/asia-pacific-roundup-pmda-puts-patients-at-heart-o  2020.12

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  • PMDA Eyes More Japan-First Approvals In Access Push Newspaper, magazine

    Informa PLC  Pink Sheet Informa Pharma Intelligence  https://pink.pharmaintelligence.informa.com/PS143361/PMDA-Eyes-More-Japan-First-Approvals-In-Access-Push  2020.11

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  • To Boost Japan-first Medical Product Approvals ~ PMDA Now Looks at Next Steps ~ Promotional material

    Pharmaceuticals and Medical Devices Agency  Chief Executive’s Statement  https://www.pmda.go.jp/english/about-pmda/0001.pdf  2020.11

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