Updated on 2025/11/01

写真a

 
HOSOJIMA Michihiro
 
Organization
Graduate School of Medical and Dental Sciences Specially Appointed Associate Professor
Title
Specially Appointed Associate Professor
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Degree

  • 医学博士 ( 2009.3   新潟大学 )

Research Interests

  • 糖尿病性腎臓病

  • 慢性腎臓病

  • メガリン

  • 急性腎障害

  • 病態栄養学

  • 近位尿細管

  • 腎臓病学

  • 糖尿病学

Research Areas

  • Life Science / Nephrology

  • Life Science / Nutrition science and health science

Research History (researchmap)

  • 新潟県立大学大学院   客員教授

    2023.4

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  • Niigata University   Graduate School of Medical and Dental Sciences   Specially Appointed Associate Professor

    2014.4

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  • Niigata University   Faculty of Agriculture   Specially Appointed Assistant Professor

    2012.4 - 2014.3

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  • Niigata University   Medical and Dental Hospital, Internal Medicine II

    2011.7 - 2014.3

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  • 小千谷総合病院

    2010.7 - 2011.6

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  • 長岡赤十字病院

    2008.7 - 2010.6

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  • Niigata University   Medical and Dental Hospital, Internal Medicine II

    2007.7 - 2008.6

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  • 県立津川病院

    2005.1 - 2005.6

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  • 長岡赤十字病院

    2004.7 - 2004.12

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  • Niigata University   Medical and Dental Hospital, Internal Medicine II

    2004.5 - 2004.6

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  • 信楽園病院

    2003.5 - 2004.4

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  • Niigata University   Medical and Dental Hospital

    2002.5 - 2003.4

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Research History

  • Niigata University   Graduate School of Medical and Dental Sciences   Specially Appointed Associate Professor

    2014.4

  • Niigata University   Faculty of Agriculture   Specially Appointed Assistant Professor

    2012.4 - 2014.3

Education

  • Niigata University   Graduate School of Medical and Dental Sciences

    2005.4 - 2009.3

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  • Niigata University   Faculty of Medicine

    - 2002.3

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Professional Memberships

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Committee Memberships

  • 日本病態栄養学会   中央プログラム委員  

    2024.11   

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    Committee type：Academic society

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  • 日本透析医学会   編集委員会 学会誌運営小委員会  

    2024.8   

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    Committee type：Academic society

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  • 日本腎臓リハビリテーション学会   腎臓リハビリテーションガイドライン作成委員  

    2024.5 - 2025.5   

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    Committee type：Academic society

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  • 厚生労働省   「日本人の食事摂取基準2025年版」策定検討会ワーキンググループ協力者  

    2023.9   

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    Committee type：Government

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  • 日本病態栄養学会   病態栄養専門管理栄養士委員会 eラーニング・セミナー開催委員  

    2023.6   

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    Committee type：Academic society

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  • 経済産業省   ヘルスケア社会実装基板整備事業「慢性腎臓病の発症・進展に関するヘルスケアサービスやデジタル技術介入の提言に資するエビデンスの構築」  

    2023.1   

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    Committee type：Government

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  • 日本腎臓学会   慢性腎臓病に対する食事療法基準作成委員会委員  

    2023.1   

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    Committee type：Academic society

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  • 新潟県   食育推進協議会委員  

    2022.12   

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    Committee type：Municipal

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  • 新潟県   糖尿病・CKD対策推進ワーキンググループ委員  

    2022.12 - 2026.3   

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    Committee type：Municipal

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  • 新潟市   糖尿病性腎症重症化予防事業 個別栄養相談アドバイザリー  

    2022.4   

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  • 日本透析医学会   栄養問題検討ワーキンググループ委員  

    2021.8   

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  • 日本腎臓学会   CKD診療ガイド・ガイドライン2023 改訂委員会  

    2020.8   

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    Committee type：Academic society

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  • 日本透析医学会   慢性維持透析患者に対する静脈栄養剤投与ならびに経管栄養に関する提言検討委員  

    2019.7 - 2020.6   

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  • 新潟県   CKD・糖尿病対策推進会議委員  

    2019.2 - 2026.3   

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    Committee type：Municipal

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  • 厚生労働省   「日本人の食事摂取基準2020年版」策定検討会ワーキンググループ協力者  

    2018.6 - 2020   

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  • 新潟県   地域保健医療計画の糖尿病・CKD対策推進ワーキンググループ委員  

    2017.7   

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    Committee type：Municipal

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  • 日本腎臓学会   サルコペニア・フレイルを合併したCKDの食事療法検討WG協力委員  

    2017.5 - 2020.3   

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    Committee type：Academic society

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  • 日本腎臓学会   CKD診療ガイド・ガイドライン2018 改訂委員会  

    2017.4 - 2020.3   

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  •   新潟市糖尿病性腎症重症化予防事業検討会議委員  

    2017.3   

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  • 新潟県   糖尿病・CKD地域連携推進部会委員  

       

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    Committee type：Municipal

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  • 新潟県   生活習慣病検診等管理指導協議会循環器等検診部会オブサーバー  

       

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    Committee type：Municipal

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Papers

  • Association Between Potential Renal Acid Load and 10-Year Mortality in Patients on Hemodialysis. International journal

    Mai Tanaka, Michihiro Hosojima, Hideyuki Kabasawa, Shin Goto, Ichiei Narita

    Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation   35 ( 2 )   344 - 352   2025.3

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    OBJECTIVES: Higher dietary acid load (DAL) has been linked to elevated incidence and progression of chronic kidney disease. However, the association between DAL and mortality in patients on maintenance hemodialysis (MHD) has not been evaluated. METHODS: We retrospectively analyzed baseline laboratory data, self-administered diet history questionnaire results, and 10-year mortality rates in 44 patients (26 men, 67.9 ± 10.4 years) on MHD who participated in a randomized, double-blind, crossover pilot trial of rice endosperm protein supplementation, which was conducted in 2013. DAL was estimated from nutrition intake using potential renal acid load (PRAL), and patients were divided into tertiles using this score. RESULTS: During the 10-year observation period, 19 patients (43%) died. A higher PRAL score was significantly associated with higher all-cause mortality. The multivariable-adjusted hazard ratio for all-cause mortality in the highest tertile of PRAL versus the lowest tertile was 3.88 (95% confidence interval [CI], 1.10-13.61). Multiple logistic regression analysis showed a significant association between higher PRAL and lower intake of green and yellow vegetables (odds ratio, 5.40; 95% CI, 1.37-21.26) and fruits (odds ratio, 4.76; 95% CI, 1.30-16.76). CONCLUSIONS: Higher PRAL is positively associated with all-cause mortality, and these associations might be affected by a lower intake of fruits and vegetables in Japanese patients on MHD.

    DOI： 10.1053/j.jrn.2024.11.001

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  • Association of Protein Intake With Discordance Between Cystatin C- and Creatinine-Based Estimated Glomerular Filtration Rates in Community-dwelling Japanese Adults. International journal

    Keiko Kabasawa, Ribeka Takachi, Michihiro Hosojima, Tomoyo Komata, Kazutoshi Nakamura, Norie Sawada, Shoichiro Tsugane, Yumi Ito, Junta Tanaka, Ichiei Narita, Kunihiro Matsushita

    Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation   2025.1

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    OBJECTIVE: Recent studies have reported the prognostic implications of the discordance between creatinine-based and cystatin C-based estimated glomerular filtration rates (eGFRcr and eGFRcys, respectively); however, the associations of protein intake with the eGFR discordance have not been investigated. The present study investigated whether protein intake was associated with the discordance between eGFRcr and eGFRcys. DESIGN AND METHODS: We cross-sectionally analyzed data from a Japanese community-based cohort including 6,143 participants (50.7% women; age range, 40-97 years). Protein intake was estimated by food groups derived from a validated food frequency questionnaire. As a measure of discordance, we modeled the ratio of eGFRcys and eGFRcr (eGFRcys divided by eGFRcr) continuously in multivariable linear regression models and categorically (<0.8, 0.8-1.1, and ≥1.2) in multinomial logistic regression models. We analyzed men and women separately given their distinct dietary patterns. RESULTS: The mean eGFR ratio was 1.15 in men and 1.19 in women. In multivariable linear regression analysis, total protein was positively associated with the eGFR ratio in men (regression coefficient, 0.005 [95% confidence interval, 0.003, 0.007]). When animal and plant proteins were analyzed separately, a significant positive association was seen for animal protein only in men (0.005 [0.003, 0.007]). The results were similar when we modeled protein intake categorically by multinomial logistic regression. CONCLUSION: This study suggests intake of dietary protein, especially animal protein in men, as a determinant of eGFR discordance. Future studies exploring eGFR discordance and health outcomes should consider simultaneously assessing dietary protein intake.

    DOI： 10.1053/j.jrn.2024.12.007

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  • Fanconi syndrome with acute proximal tubular injury induced by a dietary supplement containing beni-koji: a case series report. International journal

    Masato Habuka, Michihiro Hosojima, Yusuke Yata, Kenshiro Kurumada, Moeri Yamagiwa, Masataka Yonezawa, Masanori Sudo, Hideyuki Kabasawa, Asa Ogawa, Hitomi Hama, Yumi Ito, Naofumi Imai, Suguru Yamamoto, Akihiko Saito, Shin Goto

    BMC nephrology   25 ( 1 )   446 - 446   2024.12

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    BACKGROUND: Fanconi syndrome is a disorder of the proximal tubule that leads to malabsorption of various electrolytes and substances and is a common consequence of drug-induced nephrotoxicity. However, cases of dietary supplement-induced Fanconi syndrome are rare, and detailed reports on the evaluation of renal histology in patients with this syndrome are lacking. CASE PRESENTATION: We present two cases of dietary supplement-induced Fanconi syndrome that was confirmed by kidney biopsy. Based on their medical history and laboratory and histological findings, both cases were diagnosed as acute proximal tubular injury caused by ingestion of a lipid-lowering dietary supplement containing beni-koji leading to Fanconi syndrome. After discontinuation of the dietary supplement and correction of dehydration and electrolyte imbalance, renal function completely recovered in one case but progressed to chronic kidney disease in the other. CONCLUSIONS: Clinicians should consider dietary supplement-induced Fanconi syndrome as a differential diagnosis in patients who become ill while taking a dietary supplement. Kidney biopsy is useful for diagnosing acute tubular injury with Fanconi syndrome and investigating its pathogenesis. Patients who have developed dietary supplement-induced Fanconi syndrome require long-term monitoring to detect and prevent progression to chronic kidney disease.

    DOI： 10.1186/s12882-024-03903-5

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  • Development of sandwich enzyme-linked immunosorbent assays quantifying mouse urinary megalin, a novel proximal tubular biomarker. International journal

    Rina Sofuku, Sayaka Miyazaki, Michihiro Hosojima, Sawako Goto, Kazuya Takemoto, Hideyuki Kabasawa, Taeko Endo, Koichi Komochi, Nanako Sugita, Hiroyuki Aoki, Ryota Kobayashi, Ichiei Narita, Akihiko Saito

    Journal of immunological methods   534   113763 - 113763   2024.11

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    Megalin, a type I transmembrane protein, serves as a multi-ligand endocytic receptor in the apical membrane of proximal tubules. Its ectodomain and full-length forms are excreted into human urine, with the former being more abundant. We previously developed two types of sandwich enzyme-linked immunosorbent assays (ELISAs) utilizing monoclonal antibodies that target the amino-terminal ligand-binding domain-I and the carboxyl-terminal cytoplasmic region of human megalin, respectively. The former, termed "A-megalin" ELISA, primarily identifies ectodomains of megalin, whereas the latter, "C-megalin" ELISA, specifically recognizes full-length megalin originating from urinary extracellular vesicles. This study developed novel sandwich ELISAs to assess mouse urinary A-megalin and C-megalin, thereby facilitating studies involving these biomarkers in mouse disease models. Immunoblotting and immunohistochemistry of monoclonal antibodies against human megalin were performed to assess their compatibility with mouse megalin in novel sandwich ELISAs, which were constructed and validated using human assay protocols. Immunoblot analysis of megalin in urinary extracellular vesicles and supernatant was performed to investigate the ratio of ectodomain to full-length forms in mouse urine. Stable measurements having a precision and accuracy within 15 % were achieved in the measurement of quality control samples. A-megalin and C-megalin were detectable in the urine of C57BL/6 mice, whereas most urine samples from kidney-specific conditional megalin-knockout mice were below detection limits. Ectodomain forms of megalin were at least approximately 70 times more abundant than the full-length form, even in mouse urine. In conclusion, we successfully developed sandwich ELISAs for assessing mouse urinary A-megalin and C-megalin to evaluate primarily ectodomain and full-length forms of megalin, respectively.

    DOI： 10.1016/j.jim.2024.113763

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  • Changes in daily intake of nutrients and foods including confectionery after the initiation of empagliflozin in Japanese patients with type 2 diabetes: a pilot study. International journal

    Toshiko Murayama, Michihiro Hosojima, Hideyuki Kabasawa, Takahiro Tanaka, Nobutaka Kitamura, Mai Tanaka, Shoji Kuwahara, Yoshiki Suzuki, Ichiei Narita, Akihiko Saito

    BMC nutrition   10 ( 1 )   95 - 95   2024.7

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    INTRODUCTION: It is unclear how dietary intake changes after sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment is started in patients with type 2 diabetes. METHODS: We performed a non-controlled, open-label study that enrolled 51 patients with type 2 diabetes. The patients were newly administered empagliflozin, and their dietary habits were examined using a self-administered diet history questionnaire at the beginning of the study and after 24 weeks. We investigated the association of changes in HbA1c and body weight with changes in energy, nutrient, and food group intakes. RESULTS: At 24 weeks after the start of the study, HbA1c improved significantly and body weight decreased. In the food group, only the intake of confectionery increased, and there were no significant differences in the association between changes in HbA1c and body weight and changes in energy, nutrient, and food group intakes after 24 weeks. However, a significant negative correlation was found between change in HbA1c after 4 weeks and change in energy intake after 24 weeks, and principal component analysis showed an association between change in HbA1c levels after 4 weeks and change in energy intake and some food group intakes including confectionery after 24 weeks. CONCLUSION: In this study, after 24 weeks of treatment with empagliflozin, only intake of confectionery increased. Early assessment by dietitians after initiation of SGLT2i treatment might be important because our data suggested that the reduction in blood glucose levels after the start of empagliflozin was associated with a subsequent increase in energy intake. TRIAL REGISTRATION: University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) on September 5, 2016 (registration ID, UMIN000002309|| http://www.umin.ac.jp/ctr/ ).

    DOI： 10.1186/s40795-024-00902-5

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  • Cryo-EM structures elucidate the multiligand receptor nature of megalin. International journal

    Sawako Goto, Akihisa Tsutsumi, Yongchan Lee, Michihiro Hosojima, Hideyuki Kabasawa, Koichi Komochi, Satoru Nagatoishi, Kazuya Takemoto, Kouhei Tsumoto, Tomohiro Nishizawa, Masahide Kikkawa, Akihiko Saito

    Proceedings of the National Academy of Sciences of the United States of America   121 ( 22 )   e2318859121   2024.5

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    Megalin (low-density lipoprotein receptor-related protein 2) is a giant glycoprotein of about 600 kDa, mediating the endocytosis of more than 60 ligands, including those of proteins, peptides, and drug compounds [S. Goto, M. Hosojima, H. Kabasawa, A. Saito, Int. J. Biochem. Cell Biol. 157, 106393 (2023)]. It is expressed predominantly in renal proximal tubule epithelial cells, as well as in the brain, lungs, eyes, inner ear, thyroid gland, and placenta. Megalin is also known to mediate the endocytosis of toxic compounds, particularly those that cause renal and hearing disorders [Y. Hori et al., J. Am. Soc. Nephrol. 28, 1783-1791 (2017)]. Genetic megalin deficiency causes Donnai-Barrow syndrome/facio-oculo-acoustico-renal syndrome in humans. However, it is not known how megalin interacts with such a wide variety of ligands and plays pathological roles in various organs. In this study, we elucidated the dimeric architecture of megalin, purified from rat kidneys, using cryoelectron microscopy. The maps revealed the densities of endogenous ligands bound to various regions throughout the dimer, elucidating the multiligand receptor nature of megalin. We also determined the structure of megalin in complex with receptor-associated protein, a molecular chaperone for megalin. The results will facilitate further studies on the pathophysiology of megalin-dependent multiligand endocytic pathways in multiple organs and will also be useful for the development of megalin-targeted drugs for renal and hearing disorders, Alzheimer's disease [B. V. Zlokovic et al., Proc. Natl. Acad. Sci. U.S.A. 93, 4229-4234 (1996)], and other illnesses.

    DOI： 10.1073/pnas.2318859121

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  • Megalin-related mechanism of hemolysis-induced acute kidney injury and the therapeutic strategy. International journal

    Sawako Goto, Michihiro Hosojima, Hideyuki Kabasawa, Kaho Arai, Kazuya Takemoto, Hiroyuki Aoki, Koichi Komochi, Ryota Kobayashi, Nanako Sugita, Taeko Endo, Ryohei Kaseda, Yutaka Yoshida, Ichiei Narita, Yoshiaki Hirayama, Akihiko Saito

    The Journal of pathology   2024.5

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    Hemolysis-induced acute kidney injury (AKI) is attributed to heme-mediated proximal tubule epithelial cell (PTEC) injury and tubular cast formation due to intratubular protein condensation. Megalin is a multiligand endocytic receptor for proteins, peptides, and drugs in PTECs and mediates the uptake of free hemoglobin and the heme-scavenging protein α1-microglobulin. However, understanding of how megalin is involved in the development of hemolysis-induced AKI remains elusive. Here, we investigated the megalin-related pathogenesis of hemolysis-induced AKI and a therapeutic strategy using cilastatin, a megalin blocker. A phenylhydrazine-induced hemolysis model developed in kidney-specific mosaic megalin knockout (MegKO) mice confirmed megalin-dependent PTEC injury revealed by the co-expression of kidney injury molecule-1 (KIM-1). In the hemolysis model in kidney-specific conditional MegKO mice, the uptake of hemoglobin and α1-microglobulin as well as KIM-1 expression in PTECs was suppressed, but tubular cast formation was augmented, likely due to the nonselective inhibition of protein reabsorption in PTECs. Quartz crystal microbalance analysis revealed that cilastatin suppressed the binding of megalin with hemoglobin and α1-microglobulin. Cilastatin also inhibited the specific uptake of fluorescent hemoglobin by megalin-expressing rat yolk sac tumor-derived L2 cells. In a mouse model of hemolysis-induced AKI, repeated cilastatin administration suppressed PTEC injury by inhibiting the uptake of hemoglobin and α1-microglobulin and also prevented cast formation. Hemopexin, another heme-scavenging protein, was also found to be a novel ligand of megalin, and its binding to megalin and uptake by PTECs in the hemolysis model were suppressed by cilastatin. Mass spectrometry-based semiquantitative analysis of urinary proteins in cilastatin-treated C57BL/6J mice indicated that cilastatin suppressed the reabsorption of a limited number of megalin ligands in PTECs, including α1-microglobulin and hemopexin. Collectively, cilastatin-mediated selective megalin blockade is an effective therapeutic strategy to prevent both heme-mediated PTEC injury and cast formation in hemolysis-induced AKI. © 2024 The Pathological Society of Great Britain and Ireland.

    DOI： 10.1002/path.6284

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  • Questionnaire survey of the frequency of dietary intake during hemodialysis and the impact of COVID-19 in Japan.

    Hideyuki Kabasawa, Michihiro Hosojima, Ichiei Narita

    Clinical and experimental nephrology   28 ( 3 )   254 - 260   2024.3

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    BACKGROUND: There have been no coherent reports on the effects of dietary intake during hemodialysis in Japan. Furthermore, few studies have reported the impact of the COVID-19 pandemic on them. This study aimed to investigate dietary intake during hemodialysis and its impact on the spread of COVID-19. METHODS: This consecutive cross-sectional study included a survey of all hemodialysis facilities in the Niigata Prefecture. The survey form was sent via e-mail or fax. RESULTS: Fifty four facilities (98%) responded to the 2018 survey. Twenty-eight facilities (52%) provided meals, with 18% of all patients undergoing dialysis and 41% of patients undergoing nocturnal dialysis consuming meals during hemodialysis. In the 2020 survey, the number of facilities decreased to 17 (33%), and the number of all patients undergoing dialysis and nocturnal dialysis consuming meals decreased to 13% and 32%, respectively. In the 2022 survey, the number of facilities decreased to 14 (27%), and the number of all patients undergoing dialysis and nocturnal dialysis decreased to 9% and 19%, respectively. CONCLUSION: The COVID-19 pandemic has caused a decrease in both facilities serving meals and patients' food consumption during hemodialysis. To prevent the loss of meal opportunities, establishing safe methods for food intake and alternatives in hemodialysis facilities is necessary.

    DOI： 10.1007/s10157-023-02430-1

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  • Efficacy and safety of intradialytic parenteral nutrition using ENEFLUID® in malnourished patients receiving maintenance hemodialysis: An exploratory, multicenter, randomized, open-label study. International journal

    Hideyuki Kabasawa, Michihiro Hosojima, Eiichiro Kanda, Miho Nagai, Toshiko Murayama, Miyuki Tani, Satoru Kamoshita, Akiyoshi Kuroda, Yoshihiko Kanno

    PloS one   19 ( 12 )   e0311671   2024

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    The objective of this study was to investigate the efficacy and safety of intradialytic parenteral nutrition (IDPN) using ENEFLUID® (310 kcal, 550 mL) in mild-moderate malnutrition patients receiving maintenance hemodialysis. A total of 40 adult patients with a Nutritional Risk Index-Japanese Hemodialysis (NRI-JH) score of 5-10 were enrolled in this multicenter, randomized, open-label study. Patients in the intervention group received IDPN using ENEFLUID® via the dialysis circuit 3 times a week for 12 weeks; those in the control group did not. The primary endpoint was change in serum transthyretin (TTR). The secondary endpoints were changes in nutritional laboratory tests, nutritional parameters, food intake, plasma amino acids, and blood glucose. For both groups, mean age (72.1±11.4 years) and BMI (20.3±3.0), and median NRI-JH score [7.0 (interquartile range, 6-8)], did not differ. One patient withdrew before intervention, leaving 20 intervention and 19 control patients. Mean (95% confidence interval) change in serum TTR (mg/dL) at 12 weeks did not differ between groups: Intervention, 1.0 (-1.1-3.2); Control, -0.3 (-2.4-1.9); Intragroup difference, 1.3 (-1.7-4.3); P = 0.41. The values reflecting protein intake at 12 weeks compared to those on the study initiation day increased in the intervention group [the changes of blood urea nitrogen, 9.4 (2.6-16.2) mg/dL; P = 0.007, and normalized protein catabolic rate, 0.10 (0.02-0.18) g/kg/day; P = 0.02]. Mean food protein intake (g/kg/day) at 12 weeks increased in the intervention group and decreased in the control group, and differed between groups: Intervention, 0.12 (-0.03-0.28); Control, -0.18 (-0.43-0.08); Inter-group difference, 0.30 (0.00-0.60); P = 0.050. No adverse events occurred. In patients with mild to moderate malnutrition receiving ENEFLUID® for 12 weeks as IDPN, serum TTR was not improved, decreases in protein intake was mitigated, no adverse events occurred. Trial registration Name of the registry: Japan Registry of Clinical Trials Registration number: jRCTs031220296.

    DOI： 10.1371/journal.pone.0311671

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  • Megalin is involved in angiotensinogen-induced, angiotensin II-mediated ERK1/2 signaling to activate Na+-H+ exchanger 3 in proximal tubules. Reviewed International journal

    Sawako Goto, Yutaka Yoshida, Michihiro Hosojima, Shoji Kuwahara, Hideyuki Kabasawa, Hiroyuki Aoki, Tomomichi Iida, Ryuhei Sawada, Daisuke Ugamura, Yuta Yoshizawa, Kazuya Takemoto, Koichi Komochi, Ryota Kobayashi, Ryohei Kaseda, Eishin Yaoita, Satoru Nagatoishi, Ichiei Narita, Kouhei Tsumoto, Akihiko Saito

    Journal of hypertension   2023.9

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    BACKGROUND: Kidney angiotensin (Ang) II is produced mainly from liver-derived, glomerular-filtered angiotensinogen (AGT). Podocyte injury has been reported to increase the kidney Ang II content and induce Na+ retention depending on the function of megalin, a proximal tubular endocytosis receptor. However, how megalin regulates the renal content and action of Ang II remains elusive. METHODS: We used a mass spectrometry-based, parallel reaction-monitoring assay to quantitate Ang II in plasma, urine, and kidney homogenate of kidney-specific conditional megalin knockout (MegKO) and control (Ctl) mice. We also evaluated the pathophysiological changes in both mouse genotypes under the basal condition and under the condition of increased glomerular filtration of AGT induced by administration of recombinant mouse AGT (rec-mAGT). RESULTS: Under the basal condition, plasma and kidney Ang II levels were comparable in the two mouse groups. Ang II was detected abundantly in fresh spot urine in conditional MegKO mice. Megalin was also found to mediate the uptake of intravenously administered fluorescent Ang II by PTECs. Administration of rec-mAGT increased kidney Ang II, exerted renal extracellular signal-regulated kinase 1/2 (ERK1/2) signaling, activated proximal tubular Na+-H+ exchanger 3 (NHE3), and decreased urinary Na+ excretion in Ctl mice, whereas these changes were suppressed but urinary Ang II was increased in conditional MegKO mice. CONCLUSION: Increased glomerular filtration of AGT is likely to augment Ang II production in the proximal tubular lumen. Thus, megalin-dependent Ang II uptake should be involved in the ERK1/2 signaling that activates proximal tubular NHE3 in vivo, thereby causing Na+ retention.

    DOI： 10.1097/HJH.0000000000003555

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  • 原発性マクログロブリン血症に伴うメサンギウム増殖性腎炎にBTK阻害剤を導入した一例

    大塚 忠司, 細島 康宏, 山本 卓, 成田 一衛

    日本腎臓学会誌   65 ( 6-E )   587 - 587   2023.9

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  • 透析患者の甲状腺乳頭癌に対し,放射性ヨウ素内用療法を実施した経験例

    渡邉 和樹, 後藤 佐和子, 渡辺 博文, 細島 康宏, 野林 大幹, 飯田 倫理, 青柳 竜治, 海津 元樹, 山本 卓, 成田 一衛

    日本透析医学会雑誌   56 ( Suppl.1 )   540 - 540   2023.5

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  • 透析患者の甲状腺乳頭癌に対し,放射性ヨウ素内用療法を実施した経験例

    渡邉 和樹, 後藤 佐和子, 渡辺 博文, 細島 康宏, 野林 大幹, 飯田 倫理, 青柳 竜治, 海津 元樹, 山本 卓, 成田 一衛

    日本透析医学会雑誌   56 ( Suppl.1 )   540 - 540   2023.5

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  • The endocytosis receptor megalin: From bench to bedside. International journal

    Sawako Goto, Michihiro Hosojima, Hideyuki Kabasawa, Akihiko Saito

    The international journal of biochemistry & cell biology   157   106393 - 106393   2023.4

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    The large (∼600 kDa) endocytosis receptor megalin/low-density lipoprotein receptor-related protein 2 is highly expressed at the apical membrane of proximal tubular epithelial cells (PTECs). Megalin plays an important role in the endocytosis of various ligands via interactions with intracellular adaptor proteins, which mediate the trafficking of megalin in PTECs. Megalin mediates the retrieval of essential substances, including carrier-bound vitamins and elements, and impairment of the endocytic process may result in the loss of those substances. In addition, megalin reabsorbs nephrotoxic substances such as antimicrobial (colistin, vancomycin, and gentamicin) or anticancer (cisplatin) drugs and advanced glycation end product-modified or fatty acid-containing albumin. The megalin-mediated uptake of these nephrotoxic ligands causes metabolic overload in PTECs and leads to kidney injury. Blockade or suppression of the megalin-mediated endocytosis of nephrotoxic substances may represent a novel therapeutic strategy for drug-induced nephrotoxicity or metabolic kidney disease. Megalin reabsorbs urinary biomarker proteins such as albumin, α1-microglobulin, β2-microglobulin, and liver-type fatty acid-binding protein; thus, the above-mentioned megalin-targeted therapy may have an effect on the urinary excretion of these biomarkers. We have previously established a sandwich enzyme-linked immunosorbent assay to measure the ectodomain (A-megalin) and full-length (C-megalin) forms of urinary megalin using monoclonal antibodies against the amino- and carboxyl-terminals of megalin, respectively, and reported their clinical usefulness. In addition, there have been reports of patients with novel pathological anti-brush border autoantibodies targeting megalin in the kidney. Even with these breakthroughs in the characterization of megalin, a large number of issues remain to be addressed in future research.

    DOI： 10.1016/j.biocel.2023.106393

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  • Pathogenic variants of Alport syndrome and monogenic diabetes identified by exome sequencing in a family Reviewed

    Hirofumi Watanabe, Shin Goto, Michihiro Hosojima, Hideyuki Kabasawa, Naofumi Imai, Yumi Ito, Ichiei Narita

    Human Genome Variation   2023.2

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    DOI： 10.1038/s41439-023-00233-0

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  • A case of idiopathic nodular glomerulosclerosis successfully treated by intensive blockade of the renin-angiotensin-aldosterone system.

    Hiroki Yamaguchi, Michihiro Hosojima, Hideyuki Kabasawa, Yumi Ito, Yoshiki Suzuki, Akihiko Saito, Masaaki Arakawa, Ichiei Narita

    CEN case reports   12 ( 3 )   311 - 317   2022.12

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    Idiopathic nodular glomerulosclerosis has a poor renal prognosis and is characterized by diffuse nodular glomerulosclerotic lesions in the absence of diabetic mellitus. Here, we report the case of a 69-year-old woman with no smoking history who developed renal dysfunction and proteinuria in the absence of overt diabetes or obesity. A biopsy specimen showed nodular mesangial sclerosis with arteriolar hyalinosis and severe large-vessel arteriosclerosis, leading to a diagnosis of idiopathic nodular glomerulosclerosis. Addition of esaxerenone to her existing renin-angiotensin-aldosterone inhibitor therapy led to a rapid decrease in the proteinuria levels and the maintenance of renal function without any complications for more than a year. The results suggest that intensive renin-angiotensin-aldosterone blockade might be an effective treatment for idiopathic nodular glomerulosclerosis.

    DOI： 10.1007/s13730-022-00766-3

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

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

    Kidney360   3 ( 11 )   1861 - 1870   2022.11

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    BACKGROUND: The benefits of dietary protein restriction in CKD remain unclear, largely due to inadequate adherence in most clinical trials. We examined whether low-protein rice (LPR) previously developed to reduce the protein content of rice, a major staple food, would help improve adherence to dietary protein restriction. METHODS: This open-label, multicenter, randomized, controlled trial evaluated the efficacy of LPR use for reducing dietary protein intake (DPI) in patients with CKD stages G3aA2-G4. Participants were randomly assigned in a 1:1 ratio to an LPR or control group and were followed up for 24 weeks. Both groups received regular counseling by dietitians to help achieve a target DPI of 0.7 g/kg ideal body weight (IBW) per day. The amount of protein in LPR is about 4% of that in ordinary rice, and the participants in the LPR group were instructed to consume LPR with at least two meals per day. The primary outcome was estimated dietary protein intake (eDPI) determined using the Maroni formula. The secondary outcomes included creatinine clearance (CCr) and urinary protein on the basis of 24-hour urine collection. RESULTS: In total, 51 patients were randomized to either the LPR group or the control group. At baseline, mean age was 62.5 years, 70% were men, mean CCr was 52.0 ml/min, and mean eDPI was 0.99 g/kg IBW per day. At 24 weeks, mean eDPI decreased to 0.80 g/kg IBW per day in the LPR group and to 0.91 g/kg IBW per day in the control group, giving a between-group difference of 0.11 g/kg IBW per day (95% confidence interval, 0.03 to 0.19 g/kg IBW per day; P=0.006). There was no significant between-group difference in CCr, but urinary protein was lower at 24 weeks in the LPR group than in the control group. CONCLUSIONS: LPR is a feasible tool for efficiently reducing DPI in patients with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Randomized, Multicenter, Controlled Study for the Efficacy of Low-Protein Rice Diet in Patients with Chronic Kidney Disease, UMIN000015630.

    DOI： 10.34067/KID.0002982022

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  • Urinary A- and C-megalin predict progression of diabetic kidney disease: an exploratory retrospective cohort study. International journal

    Tomomichi Iida, Michihiro Hosojima, Hideyuki Kabasawa, Keiko Yamamoto-Kabasawa, Sawako Goto, Takahiro Tanaka, Nobutaka Kitamura, Mitsutaka Nakada, Shino Itoh, Shinya Ogasawara, Ryohei Kaseda, Yoshiki Suzuki, Ichiei Narita, Akihiko Saito

    Journal of diabetes and its complications   36 ( 11 )   108312 - 108312   2022.9

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    AIMS: Megalin, a proximal tubular endocytosis receptor, is excreted in urine in two forms: ectodomain (A-megalin) and full-length (C-megalin). We explored whether urinary megalin levels can be used as independent prognostic biomarkers in the progression of diabetic kidney disease (DKD). METHODS: The associations between baseline urinary A-megalin/creatinine (Cr) and/or C-megalin/Cr levels and the subsequent estimated glomerular filtration rate (eGFR) slope were analyzed using a generalized estimating equation. Patients were categorized into higher or lower groups based on the optimal cutoff values, obtained from a receiver operating characteristic curve, of the two forms of urinary megalin. RESULTS: We retrospectively analyzed 188 patients with type 2 diabetes. The eGFR slopes of the higher A-megalin/Cr and higher C-megalin/Cr groups were - 0.904 and -0.749 ml/min/1.73 m2/year steeper than those of the lower groups, respectively. Moreover, the eGFR slope was -1.888 ml/min/1.73 m2/year steeper in the group with both higher A- and higher C-megalin/Cr than in the other group. These results remained significant when adjusted for known urinary biomarkers (albumin, α1-microglobulin, β2-microglobulin, and N-acetyl-β-d-glucosaminidase). CONCLUSIONS: Urinary A- and C-megalin/Cr levels are likely to be prognostic biomarkers in the progression of DKD independent of other urinary biomarkers.

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  • Intradialytic parenteral nutrition using a standard amino acid solution not for renal failure in maintenance hemodialysis patients with malnutrition: a multicenter pilot study

    Ryota Yasukawa, Michihiro Hosojima, Hideyuki Kabasawa, Aya Takeyama, Daisuke Ugamura, Yoshiki Suzuki, Akihiko Saito, Ichiei Narita

    RENAL REPLACEMENT THERAPY   8 ( 1 )   2022.9

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    DOI： 10.1186/s41100-022-00432-5

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  • An exploratory clinical trial on the efficacy and safety of glucagon-like peptide-1 receptor agonist dulaglutide in patients with type 2 diabetes on maintenance hemodialysis

    Daisuke Ugamura, Michihiro Hosojima, Hideyuki Kabasawa, Naohito Tanabe, Yuta Yoshizawa, Yoshiki Suzuki, Akihiko Saito, Ichiei Narita

    RENAL REPLACEMENT THERAPY   8 ( 1 )   2022.6

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    DOI： 10.1186/s41100-022-00409-4

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  • エクソーム解析により新規変異を同定したAlport症候群と家族性若年糖尿病の一家系

    渡辺 博文, 後藤 眞, 細島 康宏, 成田 一衛

    日本腎臓学会誌   64 ( 3 )   230 - 230   2022.5

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  • Association of metabolic syndrome traits with urinary biomarkers in Japanese adults. International journal

    Keiko Kabasawa, Michihiro Hosojima, Yumi Ito, Kazuo Matsushima, Junta Tanaka, Masanori Hara, Kazutoshi Nakamura, Ichiei Narita, Akihiko Saito

    Diabetology & metabolic syndrome   14 ( 1 )   9 - 9   2022.1

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    BACKGROUND: Although metabolic syndrome traits are risk factors for chronic kidney disease, few studies have examined their association with urinary biomarkers. METHODS: Urinary biomarkers, including A-megalin, C-megalin, podocalyxin, albumin, α1-microglobulin, β2-microglobulin, and N-acetyl-β-D-glucosaminidase, were cross-sectionally assessed in 347 individuals (52.7% men) with a urine albumin-to-creatinine ratio (ACR)  < 300 mg/g in a health checkup. Metabolic syndrome traits were adopted from the National Cholesterol Education Program (third revision) of the Adult Treatment Panel criteria modified for Asians. RESULTS: Participants had a mean body mass index, estimated glomerular filtration rate (eGFR), and median ACR of 23.0 kg/m2, 74.8 mL/min/1.73 m2, and 7.5 mg/g, respectively. In age- and sex-adjusted logistic regression analysis, A-megalin and albumin were significantly associated with the clustering number of metabolic syndrome traits (3 or more). After further adjustment with eGFR, higher quartiles of A-megalin and albumin were each independently associated with the clustering number of metabolic syndrome traits (adjusted odds ratio for A-megalin: 1.30 per quartile, 95% CI 1.03-1.64; albumin: 1.42 per quartile, 95% CI 1.12-1.79). CONCLUSIONS: Both urinary A-megalin and albumin are associated with the clustering number of metabolic syndrome traits. Further research on urinary A-megalin is warranted to examine its role as a potential marker of kidney damage from metabolic risk factors.

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  • 【糖尿病性腎臓病を再考する】糖尿病性腎臓病患者におけるたんぱく質制限

    蒲澤 秀門, 細島 康宏, 鈴木 芳樹

    腎臓内科   15 ( 1 )   64 - 69   2022.1

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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. International journal

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

    Journal of the American College of Nutrition   41 ( 7 )   1 - 11   2021.8

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    Chronic kidney disease (CKD) impairs the anti-inflammatory effects of high-density lipoprotein (HDL) and increases cardiovascular mortality. Though the potential role of dietary interventions to manage HDL is well studied, the clinical trials aimed to increase HDL levels have failed to reduce cardiovascular risk, rendering HDL function to be explored as a more relevant clinical parameter. This study investigates the effects of rice endosperm protein (REP), a plant-based protein, on the anti-inflammatory properties of HDL and renal injury-driven atherosclerosis in comparison with casein, an animal protein. Ten-week-old apolipoprotein E-deficient hyperlipidemic mice underwent uninephrectomy. The mice (n = 6 each) were pair-fed a normal casein-based diet or a REP-based diet (both with 20.0% protein content) for seven weeks. Atherosclerotic lesions were detected by en face Sudan IV staining of the aorta. The number and sizes of the atherosclerotic lesions were significantly lower in the REP-based diet-fed group than the casein-based diet-fed group (p = 0.038). However, the REP-based diet neither elicited an ameliorative effect on kidney function or histology nor impacted the cholesterol profiles. Furthermore, HDL from the REP-based diet-fed mice significantly suppressed the inflammatory cytokine response of human umbilical vein endothelial cells than that from the casein-based diet-fed mice (MCP-1, p = 0.010; IL-6, p = 0.011; IL-1β, p = 0.028). The REP-based diet has a higher potential to lessen the atherosclerotic lesions accelerated by renal mass reduction than a casein-based diet, which could be associated with the anti-inflammatory effects of HDL.

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  • Measurement of Plasma Glucagon Levels Using Mass Spectrometry in Patients with Type 2 Diabetes on Maintenance Hemodialysis. International journal

    Yuta Yoshizawa, Michihiro Hosojima, Hideyuki Kabasawa, Naohito Tanabe, Atsushi Miyachi, Hitoshi Hamajima, Eri Mieno, Masaki Kobayashi, Tadahiro Kitamura, Ichiei Narita, Akihiko Saito

    Kidney & blood pressure research   46 ( 5 )   1 - 5   2021.8

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    BACKGROUND: Recently, attention has been focused on the effect of glucagon on blood glucose variability. The dynamics of glucagon have attracted attention as a new target in the treatment of diabetes patients. However, the dynamics of glucagon in hemodialysis (HD) patients with type 2 diabetes mellitus (T2DM) remain unclear. OBJECTIVES: The aim of this study was to assess the dynamics of glucagon in HD patients with T2DM. MATERIALS AND METHODS: We measured plasma glucagon in HD patients with T2DM by liquid chromatography-high-resolution mass spectrometry (LC-HRMS), sandwich enzyme-linked immunosorbent assay (ELISA), and radioimmunoassay (RIA). The glucagon levels measured by each method were compared. We used the glucagon levels determined by our developed LC-HRMS method as the standard in this study. RESULTS: Plasma glucagon levels measured by LC-HRMS before HD were significantly higher than those measured after HD. Plasma glucagon levels measured using sandwich ELISA had a significantly higher correlation with those measured using LC-HRMS compared with RIA. CONCLUSIONS: This was the first study to assess glucagon levels in HD patients with T2DM using LC-HRMS, which is considered a highly accurate method. Sandwich ELISA was shown to measure glucagon levels accurately as well.

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  • Urinary FABP1 is a biomarker for impaired proximal tubular protein reabsorption and is synergistically enhanced by concurrent liver injury. International journal

    Ryo Kawakami, Miki Matsui, Ayumu Konno, Ryosuke Kaneko, Shreya Shrestha, Suman Shrestha, Hiroaki Sunaga, Hirofumi Hanaoka, Sawako Goto, Michihiro Hosojima, Hideyuki Kabasawa, Masaru Obokata, Norimichi Koitabashi, Hiroki Matsui, Tsutomu Sasaki, Akihiko Saito, Motoko Yanagita, Hirokazu Hirai, Masahiko Kurabayashi, Tatsuya Iso

    The Journal of pathology   255 ( 4 )   362 - 373   2021.8

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    Urinary fatty acid binding protein 1 (FABP1, also known as liver-type FABP) has been implicated as a biomarker of acute kidney injury (AKI) in humans. However, the precise biological mechanisms underlying its elevation remain elusive. Here, we show that urinary FABP1 primarily reflects impaired protein reabsorption in proximal tubule epithelial cells (PTECs). Bilateral nephrectomy resulted in a marked increase in serum FABP1 levels, suggesting that the kidney is an essential organ for removing serum FABP1. Injected recombinant FABP1 was filtered through the glomeruli and robustly reabsorbed via the apical membrane of PTECs. Urinary FABP1 was significantly elevated in mice devoid of megalin, a giant endocytic receptor for protein reabsorption. Elevation of urinary FABP1 was also observed in patients with Dent disease, a rare genetic disease characterized by defective megalin function in PTECs. Urinary FABP1 levels were exponentially increased following acetaminophen overdose, with both nephrotoxicity and hepatotoxicity observed. FABP1-deficient mice with liver-specific overexpression of FABP1 showed a massive increase in urinary FABP1 levels upon acetaminophen injection, indicating that urinary FABP1 is liver-derived. Lastly, we employed transgenic mice expressing diphtheria toxin receptor (DT-R) either in a hepatocyte- or in a PTEC-specific manner, or both. Upon administration of diphtheria toxin (DT), massive excretion of urinary FABP1 was induced in mice with both kidney and liver injury, while mice with either injury type showed marginal excretion. Collectively, our data demonstrated that intact PTECs have a considerable capacity to reabsorb liver-derived FABP1 through a megalin-mediated mechanism. Thus, urinary FABP1, which is synergistically enhanced by concurrent liver injury, is a biomarker for impaired protein reabsorption in AKI. These findings address the use of urinary FABP1 as a biomarker of histologically injured PTECs that secrete FABP1 into primary urine, and suggest the use of this biomarker to simultaneously monitor impaired tubular reabsorption and liver function. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

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  • Plasma Globotriaosylsphingosine and α-Galactosidase A Activity as a Combined Screening Biomarker for Fabry Disease in a Large Japanese Cohort. International journal

    Hiroki Maruyama, Atsumi Taguchi, Mariko Mikame, Atsushi Izawa, Naoki Morito, Kazufumi Izaki, Toshiyuki Seto, Akifumi Onishi, Hitoshi Sugiyama, Norio Sakai, Kenji Yamabe, Yukio Yokoyama, Satoshi Yamashita, Hiroshi Satoh, Shigeru Toyoda, Michihiro Hosojima, Yumi Ito, Ryushi Tazawa, Satoshi Ishii

    Current issues in molecular biology   43 ( 1 )   389 - 404   2021.6

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    Fabry disease is an X-linked disorder of α-galactosidase A (GLA) deficiency. Our previous interim analysis (1 July 2014 to 31 December 2015) revealed plasma globotriaosylsphingosine as a promising primary screening biomarker for Fabry disease probands. Herein, we report the final results, including patients enrolled from 1 January to 31 December 2016 for evaluating the potential of plasma globotriaosylsphingosine and GLA activity as a combined screening marker. We screened 5691 patients (3439 males) referred from 237 Japanese specialty clinics based on clinical findings suggestive of Fabry disease using plasma globotriaosylsphingosine and GLA activity as primary screening markers, and GLA variant status as a secondary screening marker. Of the 14 males who tested positive in the globotriaosylsphingosine screen (≥2.0 ng/mL), 11 with low GLA activity (<4.0 nmol/h/mL) displayed GLA variants (four classic, seven late-onset) and one with normal GLA activity and no pathogenic variant displayed lamellar bodies in affected organs, indicating late-onset biopsy-proven Fabry disease. Of the 19 females who tested positive in the globotriaosylsphingosine screen, eight with low GLA activity displayed GLA variants (six classic, two late-onset) and five with normal GLA activity displayed a GLA variant (one classic) and no pathogenic variant (four late-onset biopsy-proven). The combination of plasma globotriaosylsphingosine and GLA activity can be a primary screening biomarker for classic, late-onset, and late-onset biopsy-proven Fabry disease probands.

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  • Effects of the Once-Weekly DPP4 Inhibitor Omarigliptin on Glycemic Control in Patients with Type 2 Diabetes Mellitus on Maintenance Hemodialysis: A 24-Week Open-Label, Multicenter Randomized Controlled Study. International journal

    Yuta Yoshizawa, Michihiro Hosojima, Hideyuki Kabasawa, Naohito Tanabe, Daisuke Ugamura, Yutaka Koda, Hisaki Shimada, Tetsuya Takasawa, Takahito Ito, Tadahiro Kitamura, Masaki Kobayashi, Yoshiki Suzuki, Ichiei Narita, Akihiko Saito

    Diabetes therapy : research, treatment and education of diabetes and related disorders   12 ( 3 )   655 - 667   2021.3

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    INTRODUCTION: Dipeptidyl peptidase 4 (DPP4) inhibitors are widely used in patients with type 2 diabetes mellitus (T2DM) on maintenance hemodialysis (HD), but the efficacy of the once-weekly DPP4 inhibitor omarigliptin is not known. METHODS: This prospective, randomized, open-label, parallel-group, non-inferiority/superiority, once-daily DPP4 inhibitor linagliptin-controlled, multicenter study examined glycemic control and safety of omarigliptin (UMIN000024284). Sample size was calculated to confirm non-inferiority in terms of changes in glycated hemoglobin (HbA1c). We enrolled 33 patients with T2DM on maintenance HD who had been treated with linagliptin for at least 3 months. The patients were randomized to receive omarigliptin (12.5 mg/week; n = 16) or linagliptin (5 mg/day; n = 17). Primary endpoints were changes in HbA1c and glycoalbumin (GA) over 24 weeks. RESULTS: Differences in the mean change in primary endpoint values between the omarigliptin and linagliptin groups were - 0.61% [- 1.14, - 0.09] for HbA1c, with a two-tailed upper 95% limit (i.e., one-tailed 97.5% upper limit) of 0.25%, below the non-inferiority limit, and - 1.67% [- 4.23, + 0.88] for GA, with a two-tailed upper 95% limit of 0.75%, above the non-inferiority limit. At 24 weeks, the omarigliptin group showed significantly greater reduction in HbA1c than the linagliptin group (- 0.2% ± 0.6% vs. 0.4% ± 0.8%, two-tailed p = 0.024) and significantly greater reduction in blood glucose after a single HD session (- 18.4 ± 31.4 mg/dL vs. 25.2 ± 59.5 mg/dL, respectively, two-tailed p = 0.019). No subjects in the omarigliptin group developed hypoglycemia. CONCLUSIONS: Our data showed that omarigliptin was non-inferior to linagliptin in glycemic control. Omarigliptin is feasible for glycemic control in patients with T2DM on maintenance HD. CLINICAL TRIALS REGISTRATION: UMIN000024284.

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

    Masashi Arita, Satoshi Watanabe, Nobumasa Aoki, Shoji Kuwahara, Ryo Suzuki, Sawako Goto, Yuko Abe, Miho Takahashi, Miyuki Sato, Satoshi Hokari, Aya Ohtsubo, Satoshi Shoji, Koichiro Nozaki, Kosuke Ichikawa, Rie Kondo, Masachika Hayashi, Yasuyoshi Ohshima, Hideyuki Kabasawa, Michihiro Hosojima, Toshiyuki Koya, Akihiko Saito, Toshiaki Kikuchi

    Scientific reports   11 ( 1 )   750 - 750   2021.1

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    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.

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  • Effects of DPP-4 Inhibitors on Blood Glucose Variability in Japanese Patients with Type 2 Diabetes on Maintenance Hemodialysis: A Prospective Observational Exploratory Study. International journal

    Tomomi Ishikawa-Tanaka, Michihiro Hosojima, Hideyuki Kabasawa, Ryohei Kaseda, Ryota Yasukawa, Yusuke Yata, Shoji Kuwahara, Emiko Kono, Takuma Takata, Noriaki Iino, Takahiro Tanaka, Nobutaka Kitamura, Yoshiki Suzuki, Akihiko Saito, Ichiei Narita

    Diabetes therapy : research, treatment and education of diabetes and related disorders   11 ( 12 )   2845 - 2861   2020.12

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    INTRODUCTION: The precise blood glucose (BG) profile of hemodialysis patients is unclear, as is the effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors in hemodialysis patients with type 2 diabetes. Here, we used continuous glucose monitoring (CGM) to evaluate BG variability in these patients and to assess the efficacy of DPP-4 inhibitors, particularly during hemodialysis sessions and at nighttime (UMIN000012638). METHODS: We examined BG profiles using CGM in 31 maintenance hemodialysis patients with type 2 diabetes. Differences between patients with and without DPP-4 inhibitors (n = 15 and 16, respectively) were analyzed using a linear mixed-effects model to assess changes in glucose levels in 5-min intervals. RESULTS: The model revealed that DPP-4 inhibitor use was significantly associated with suppression of a rapid drop in glucose levels, both with and without adjustment for BG levels at the start of hemodialysis. Moreover, the model revealed that the two groups differed significantly in the pattern of changes in BG levels from 0:00 to 6:55 am. DPP-4 inhibitors suppressed the tendency for subsequent nocturnal hypoglycemia. CONCLUSIONS: This prospective observational exploratory study showed that DPP-4 inhibitors could suppress BG variability during hemodialysis sessions as well as subsequent nocturnal changes in patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov identifier, UMIN000012638.

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  • Rice bran protein ameliorates diabetes, reduces fatty liver, and has renoprotective effects in Zucker diabetic fatty rats Reviewed

    Kubota M, Watanabe R, Hosojima M, Saito A, Sasou A, Masumura T, Harada Y, Hashimoto H, Fujimura S, Kadowaki M

    Journal of Functional Foods   70   103981 - 103981   2020

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    DOI： 10.1016/j.jff.2020.103981

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

    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 )   1170 - 1170   2019.12

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    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.

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  • 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

    Higuchi Y, Hosojima M, Kabasawa H, Kuwahara S, Goto S, Toba K, Kaseda R, Tanaka T, Kitamura N, Takihara H, Okuda S, Taniguchi M, Arao H, Narita I, Saito A

    Nutrients   11 ( 12 )   2019.12

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    Obesity and related disorders, which are increasing in adults worldwide, are closely linked to childhood diet and are associated with chronic inflammation. Rice endosperm protein (REP) intake during adulthood has been reported to improve lipid metabolism and suppress the progression of diabetic kidney disease in animal models. However, the effects of REP intake during childhood on adulthood health are unclear. Therefore, we used a mouse model to experimentally investigate the preconditioning effects of REP intake during childhood on the development of obesity and related disorders in adulthood. Male C57BL/6J mice were pair-fed a normal-fat diet containing casein or REP during the juvenile period and then a high-fat diet (HFD) containing casein or REP during adulthood. Mice fed REP during the juvenile period showed better body weight, blood pressure, serum lipid profiles, lipopolysaccharide (LPS)-binding protein levels, and glucose tolerance in adulthood than those fed casein during the juvenile period. HFD-induced renal tubulo-glomerular alterations and hepatic microvesicular steatosis were less evident in REP-fed mice than in casein-fed ones. REP intake during the juvenile period improved HFD-induced dysbiosis (i.e., Escherichia genus proliferation and reduced gut microbiota diversity), thereby suppressing endotoxin-related chronic inflammation. Indeed, REP-derived peptides showed antibacterial activity against Escherichia coli, a major producer of LPS. In conclusion, REP supplementation during the juvenile period may regulate the gut microbiota and thus suppress the development of obesity and related disorders in adulthood in mice.

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  • 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 International journal

    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 )   421 - 421   2019.11

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    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.

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  • Association of estimated dietary acid load with albuminuria in Japanese adults: a cross-sectional study. Reviewed International journal

    Kabasawa K, Hosojima M, Takachi R, Nakamura K, Ito Y, Saito A, Sawada N, Tsugane S, Tanaka J, Narita I

    BMC nephrology   20 ( 1 )   194 - 194   2019.5

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    BACKGROUND: Acid-base imbalance might promote the progression of chronic kidney disease (CKD), but whether nutrient-derived dietary acid load increases the risk of albuminuria or even high normoalbuminuria is unclear. METHODS: A Japanese cohort comprising 3250 men and 3434 women aged 40-97 years with urine albumin-to-creatinine ratio (ACR) < 33.9 mg/mmol or estimated glomerular filtration rate ≥ 15 ml/min/1.73 m2 were assessed. We performed a cross-sectional evaluation of the association between net endogenous acid production (NEAP), estimated as dietary protein to potassium content ratio, and the presence of high normoalbuminuria (ACR: 1.13-3.38 mg/mmol) or microalbuminuria. RESULTS: Median NEAP was 43.4 (interquartile range (IQR): 34.2-53.4) mEq/day in men and 35.0 (IQR: 27.7-43.6) mEq/day in women. Median ACR was 1.11 (IQR: 0.57-2.49) mg/mmol in men and 1.47 (IQR: 0.82-2.83) mg/mmol in women. In multivariate analysis, the adjusted odds ratio of the highest versus lowest NEAP quartile for microalbuminuria was 1.47 (95% confidence interval (CI): 1.08-1.99) in men and 1.54 (95% CI: 1.11-2.14) in women. For high normoalbuminuria or microalbuminuria, the adjusted odds ratio was 1.28 (95% CI: 1.02-1.59) in men and 1.39 (95% CI: 1.11-1.74) in women. From nutrient composition analysis, subjects with the highest potassium intake, but not protein intake, had lower adjusted odds ratios for the presence of microalbuminuria than those in the lowest quartile for potassium intake. CONCLUSIONS: Higher NEAP was associated with albuminuria and its association might negatively relate to potassium intake in an adult Japanese population.

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    Other Link： http://link.springer.com/article/10.1186/s12882-019-1352-8/fulltext.html

  • Successful treatment of gamma 1 heavy chain deposition disease with bortezomib and dexamethasone

    Masanori Sudo, Takuya Wakamatsu, Tomomi Ishikawa, Masato Habuka, Michihiro Hosojima, Suguru Yamamoto, Yumi Ito, Naofumi Imai, Yoshikatsu Kaneko, Akira Shimizu, Ichiei Narita

    Human Pathology: Case Reports   15   99 - 104   2019.3

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  • Cryofibrinogen-associated glomerulonephritis diagnosed by mass spectrometry and immunoelectron microscopy

    Masanori Sudo, Yuichi Sakamaki, Michihiro Hosojima, Suguru Yamamoto, Yumi Ito, Naofumi Imai, Yoshikatsu Kaneko, Shin Goto, Chih Ping Li, Akira Shimizu, Ichiei Narita

    Human Pathology: Case Reports   15   83 - 87   2019.3

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  • β2-Microglobulin and Neutrophil Gelatinase-Associated Lipocalin, Potential Novel Urine Biomarkers in Periodontitis: A Cross-Sectional Study in Japanese. Reviewed International journal

    Mayuka Nakajima, Michihiro Hosojima, Koichi Tabeta, Sayuri Miyauchi, Miki Yamada-Hara, Naoki Takahashi, Haruna Miyazawa, Yumi Matsuda-Matsukawa, Keisuke Sato, Noriko Sugita, Yasutaka Komatsu, Tomomi Ishikawa, Kazuhiro Akiishi, Kazuhisa Yamazaki, Kiminori Kato, Akihiko Saito, Hiromasa Yoshie

    International journal of dentistry   2019   1394678 - 1394678   2019

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    Objectives: Several serum biomarkers have been reported to increase in periodontitis patients as possible mediators linking periodontal inflammation to systemic diseases. However, the relationship between periodontitis and urine biomarkers is still unclear. The aim of this cross-sectional study was to investigate potential urine biomarkers of periodontitis in a Japanese population. Materials and Methods: This study included 108 male subjects, and microbiological and clinical parameters were evaluated as a periodontitis marker. The correlation between nine urine biomarkers (typically used to diagnose kidney disease) and periodontal parameters was analyzed. Based on the findings, β2-microglobulin (β2-MG) and neutrophil gelatinase-associated lipocalin (NGAL) were selected for comparison and multivariate regression analysis, and the Kruskal-Wallis test followed by Bonferroni correction was used to identify differences in their concentrations between the three periodontitis groups (severe, moderate, and no/mild periodontitis). Results: β2-MG and NGAL exhibited a significant correlation with clinical parameters of periodontitis. The prevalence of clinical parameters such as bleeding on probing and number of sites with probing depth (PD) ≥ 6 mm were greater in the β2-MG high group (≥300 μg/g creatinine) than in the normal group (P=0.017 and 0.019, respectively). Multivariate regression analysis indicated that the number of sites with PD ≥ 6 mm was independently associated with urine β2-MG. Moreover, the number of sites with the clinical attachment level (CAL) ≥ 6 mm was greater in the NGAL high group (highest quartile) (P=0.041). Multivariate regression analysis showed that the number of sites with CAL ≥ 6 mm was associated independently with urine NGAL. Finally, β2-MG was significantly higher in the severe periodontitis subjects compared to the no/mild periodontitis subjects. Conclusion: The significant association between urine β2-MG or NGAL and periodontitis was revealed. These biomarkers can potentially be used to screen for or diagnose periodontitis. This trial is registered with the UMIN Clinical Trials Registry UMIN000013485.

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  • Increased serum PCSK9, a potential biomarker to screen for periodontitis, and decreased total bilirubin associated with probing depth in a Japanese community survey Reviewed

    K. Tabeta, M. Hosojima, M. Nakajima, S. Miyauchi, H. Miyazawa, N. Takahashi, Y. Matsuda, N. Sugita, Y. Komatsu, K. Sato, T. Ishikawa, K. Akiishi, K. Yamazaki, K. Kato, A. Saito, H. Yoshie

    Journal of Periodontal Research   53 ( 3 )   446 - 456   2018.6

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  • ケース・スタディ 呼吸苦のため維持血液透析から腹膜透析に移行した1例

    保川 亮太, 山崎 美穂子, 田崎 和之, 鈴木 靖, 若松 拓也, 細島 康宏, 保坂 聖子, 山本 卓, 後藤 眞, 成田 一衛

    臨床透析   34 ( 2 )   223 - 227   2018.2

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  • メガリンを「入り口」とする糖尿病性腎臓病の発症・進展機序とメガリン抑制薬の検討

    桑原 頌治, 細島 康宏, 飯田 倫理, 蒲澤 秀門, 忰田 亮平, 斎藤 亮彦

    日本病態栄養学会誌   21 ( Suppl. )   S - 70   2018.1

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  • [Exosomal biomarkers for kidney disease.] Reviewed

    Hosojima M, Kabasawa H, Kuwahara S, Saito A

    Clinical calcium   28 ( 2 )   252 - 259   2018

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    Development of minimally invasive biomarkers is necessary for early detection, prognosis prediction, severity assessment and treatment monitoring in different kidney diseases. Recently, many studies have been conducted worldwide on marker proteins and micro RNA(miRNA)contained in urinary extracellular vesicles(EVs)including exosomes. This article reviews urinary EV-contained biomarkers, including proximal tubular endocytic receptor megalin, for kidney diseases such as diabetic nephropathy.

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  • 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   7 ( 1 )   18003 - 18003   2017.12

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    DOI： 10.1038/s41598-017-18340-8

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  • A case of non-episodic angioedema with eosinophilia induced by influenza vaccine. Reviewed International journal

    Ryota Hayashi, Naoko Shimomura, Michihiro Hosojima, Akari Sakai, Yohya Shigehara, Riichiro Abe

    European journal of dermatology : EJD   27 ( 5 )   554 - 555   2017.10

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  • 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   28 ( 6 )   1783 - 1791   2017.6

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    DOI： 10.1681/ASN.2016060606

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

    Shankhajit De, Shoji Kuwahara, Michihiro Hosojima, Tomomi Ishikawa, Ryohei Kaseda, Piyali Sarkar, Yusuke Yoshioka, Hideyuki Kabasawa, Tomomichi Iida, Sawako Goto, Koji Toba, Yuki Higuchi, Yoshiki Suzuki, Masanori Hara, Hiroyuki Kurosawa, Ichiei Narita, Yoshiaki Hirayama, Takahiro Ochiya, Akihiko Saito

    DIABETES   66 ( 5 )   1391 - 1404   2017.5

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  • Comparison of methods of steroid administration combined with tonsillectomy for IgA nephropathy patients Reviewed

    Hirofumi Watanabe, Shin Goto, Daisuke Kondo, Takuma Takata, Hajime Yamazaki, Michihiro Hosojima, Suguru Yamamoto, Yoshikatsu Kaneko, Ryuji Aoyagi, Ichiei Narita

    CLINICAL AND EXPERIMENTAL NEPHROLOGY   21 ( 2 )   257 - 265   2017.4

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  • SGLT2阻害薬開始の前後で食事記録を確認できた肥満2型糖尿病の一例 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   20 ( 1 )   167 - 172   2017.4

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  • BENEFICIAL EFFECTS OF RICE ENDOSPERM PROTEIN ON CHRONIC KIDNEY DISEASE-MINERAL AND BONE DISORDER (CKD-MBD) IN ZUCKER DIABETIC FATTY RATS Reviewed

    Reiko Watanabe, Masatoshi Kubota, Shogo Sugaki, Michihiro Hosojima, Akihiko Saito, Mikio Fujii, Ichiro Sasagawa, Shinobu Fujimura, Motoni Kadowaki

    ANNALS OF NUTRITION AND METABOLISM   71   1218 - 1218   2017

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  • Glucose Variability Based on Continuous Glucose Monitoring Assessment Is Associated with Postoperative Complications after Cardiovascular Surgery Reviewed

    Hiroki Sato, Michihiro Hosojima, Tomomi Ishikawa, Kenji Aoki, Takeshi Okamoto, Akihiko Saito, Masanori Tsuchida

    ANNALS OF THORACIC AND CARDIOVASCULAR SURGERY   23 ( 5 )   239 - 247   2017

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  • The Assessment of the Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Patients with Glucocorticoid-induced Diabetes by Continuous Glucose Monitoring Reviewed

    Yusuke Yata, Michihiro Hosojima, Hideyuki Kabasawa, Tomomi Ishikawa, Ryohei Kaseda, Noriaki Iino, Yoshiki Suzuki, Akihiko Saito, Ichiei Narita

    INTERNAL MEDICINE   56 ( 19 )   2555 - 2562   2017

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  • Rice endosperm protein slows progression of fatty liver and diabetic nephropathy in Zucker diabetic fatty rats Reviewed International journal

    Masatoshi Kubota, Reiko Watanabe, Miki Yamaguchi, Michihiro Hosojima, Akihiko Saito, Mikio Fujii, Shinobu Fujimura, Motoni Kadowaki

    BRITISH JOURNAL OF NUTRITION   116 ( 8 )   1326 - 1335   2016.10

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

    Shoji Kuwahara, Michihiro Hosojima, Reika Kaneko, Hiroyuki Aoki, Daisuke Nakano, Taiji Sasagawa, Hideyuki Kabasawa, Ryohei Kaseda, Ryota Yasukawa, Tomomi Ishikawa, Akiyo Suzuki, Hiroyoshi Sato, Shun Kageyama, Takahiro Tanaka, Nobutaka Kitamura, Ichiei Narita, Masaaki Komatsu, Akira Nishiyama, Akihiko Saito

    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY   27 ( 7 )   1996 - 2008   2016.7

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  • Beneficial effects of rice endosperm protein intake in Japanese men with risk factors for metabolic syndrome: a randomized, crossover clinical trial

    Michihiro Hosojima, Ryohei Kaseda, Hazuki Kondo, Mikio Fujii, Masatoshi Kubota, Reiko Watanabe, Naohito Tanabe, Motoni Kadowaki, Yoshiki Suzuki, Akihiko Saito

    BMC Nutrition   2 ( 1 )   2016.5

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  • Protective effect of composite earthworm powder against diabetic complications via increased fibrinolytic function and improvement of lipid metabolism in ZDF rats Reviewed International journal

    Tomoko Kawakami, Airi Fujikawa, Yohei Ishiyama, Michihiro Hosojima, Akihiko Saito, Masatoshi Kubota, Shinobu Fujimura, Motoni Kadowaki

    BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   80 ( 10 )   1980 - 1989   2016

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  • Benefits of a 12-week lifestyle modification program including diet and combined aerobic and resistance exercise on albuminuria in diabetic and non-diabetic Japanese populations Reviewed

    Keiko Yamamoto-Kabasawa, Michihiro Hosojima, Yusuke Yata, Mariko Saito, Noriko Tanaka, Junta Tanaka, Naohito Tanabe, Ichiei Narita, Masaaki Arakawa, Akihiko Saito

    CLINICAL AND EXPERIMENTAL NEPHROLOGY   19 ( 6 )   1079 - 1089   2015.12

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  • Reduction of Albuminuria by Sitagliptin Is Associated with Improvement of Renal Proximal Tubular Function in Patients with Type 2 Diabetes Reviewed

    Hosojima Michihiro, Sasagawa Taiji, Kabasawa Hideyuki, Ishikawa Tomomi, Kaseda Ryohei, Suzuki Yoshiki, Narita Ichiei, Kurosawa Hiroyuki, Hirayama Yoshiaki, Saito Akihiko

    DIABETES   64   A151   2015.6

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  • 皮下多発結節を有しErdheim-Chester病と診断した1例

    遠藤 麻巳子, 高井 千夏, 朝川 勝明, 渡辺 博文, 忰田 亮平, 細島 康宏, 川村 和子, 風間 順一郎, 成田 一衛, 清水 彩子, 苅谷 直之, 梅津 哉

    新潟医学会雑誌   129 ( 5 )   290 - 290   2015.5

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  • 還ってきた腎臓 3ヵ月に及ぶ急性血液浄化から離脱しえた全身熱傷に伴う急性腎障害の一例

    伊藤 友美, 大塚 忠司, 渡邉 博文, 高井 千夏, 細島 康宏, 忰田 亮平, 川村 和子, 風間 順一郎

    新潟急性血液浄化研究会抄録集   1回   9 - 9   2014.11

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  • GFR ESTIMATION BY URINARY SOLUBLE MEGALIN

    Hiwatashi, Akira, Hagiwara, Masahiro, Tsuruoka, Syuichi, Usui, Joichi, Nagai, Kei, Kai, Hirayasu, Morito, Naoki, Saito, Chie, Yoh, Keigyo, Hosojima, Michihiro, Saito, Akihiko, Yamagata, Kunihiro

    NEPHROLOGY DIALYSIS TRANSPLANTATION   28 ( 1 )   145 - 145   2013.5

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  • Protective effects of alkali-extracted rice protein on diabetic nephropathy in obese type 2 diabetic rats Reviewed

    Kubota Masatoshi, Watanabe Reiko, Yamaguchi Miki, Hosojima Michihiro, Saito Akihiko, Fujii Mikio, Fujimura Shinobu, Kadowaki Motoni

    FASEB JOURNAL   27   2013.4

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  • Significance of Urinary Full-Length and Ectodomain Forms of Megalin in Patients With Type 2 Diabetes Reviewed International journal

    Shinya Ogasawara, Michihiro Hosojima, Ryohei Kaseda, Hideyuki Kabasawa, Keiko Yamamoto-Kabasawa, Hiroyuki Kurosawa, Hiroyoshi Sato, Noriaki Iino, Tetsuro Takeda, Yoshiki Suzuki, Ichie Narita, Kunihiro Yamagata, Yasuhiko Tomino, Fumitake Gejyo, Yoshiaki Hirayama, Sakari Sekine, Akihiko Saito

    DIABETES CARE   35 ( 5 )   1112 - 1118   2012.5

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    DOI： 10.2337/dc11-1684

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  • Role of Megalin and Cubilin in the Metabolism of Vitamin D-3 Reviewed International journal

    Ryohei Kaseda, Michihiro Hosojima, Hiroyoshi Sato, Akihiko Saito

    THERAPEUTIC APHERESIS AND DIALYSIS   15   14 - 17   2011.6

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    DOI： 10.1111/j.1744-9987.2011.00920.x

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  • Megalin is downregulated via LPS-TNF-alpha-ERK1/2 signaling pathway in proximal tubule cells Reviewed International journal

    Aya Takeyama, Hiroyoshi Sato, Taeko Soma-Nagae, Hideyuki Kabasawa, Akiyo Suzuki, Keiko Yamamoto-Kabasawa, Michihiro Hosojima, Reika Kaneko, Fumie Higuchi, Ryohei Kaseda, Shinya Ogasawara, Ichiei Narita, Akihiko Saito

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   407 ( 1 )   108 - 112   2011.4

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    DOI： 10.1016/j.bbrc.2011.02.118

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  • Proximal tubule cell hypothesis for cardiorenal syndrome in diabetes. Reviewed International journal

    Saito A, Kaseda R, Hosojima M, Sato H

    International journal of nephrology   2011   957164 - 957164   2010.12

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    Incidence of cardiovascular disease (CVD) is remarkably high among patients with chronic kidney disease (CKD), even in the early microalbuminuric stages with normal glomerular filtration rates. Proximal tubule cells (PTCs) mediate metabolism and urinary excretion of vasculotoxic substances via apical and basolateral receptors and transporters. These cells also retrieve vasculoprotective substances from circulation or synthesize them for release into the circulation. PTCs are also involved in the uptake of sodium and phosphate, which are critical for hemodynamic regulation and maintaining the mineral balance, respectively. Dysregulation of PTC functions in CKD is likely to be associated with the development of CVD and is linked to the progression to end-stage renal disease. In particular, PTC dysfunction occurs early in diabetic nephropathy, a leading cause of CKD. It is therefore important to elucidate the mechanisms of PTC dysfunction to develop therapeutic strategies for treating cardiorenal syndrome in diabetes.

    DOI： 10.4061/2011/957164

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  • 血液透析中の再発進行食道癌に対しDocetaxel/Nedaplatin併用療法を施行し嚥下障害の改善が得られた1例

    三浦 智史, 細島 康宏, 中村 潤一郎, 山田 聡志, 中澤 保子, 大関 裕, 三浦 努, 柳 雅彦, 山崎 肇, 高橋 達

    癌と化学療法   37 ( 5 )   883 - 885   2010.5

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  • Megalin and nonmuscle myosin heavy chain IIA interact with the adaptor protein Disabled-2 in proximal tubule cells Reviewed International journal

    Kiyoko Hosaka, Tetsuro Takeda, Noriaki Iino, Michihiro Hosojima, Hiroyoshi Sato, Ryohei Kaseda, Keiko Yamamoto, Asako Kobayashi, Fumitake Gejyo, Akihiko Saito

    KIDNEY INTERNATIONAL   75 ( 12 )   1308 - 1315   2009.6

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    DOI： 10.1038/ki.2009.85

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  • Regulation of Megalin Expression in Cultured Proximal Tubule Cells by Angiotensin II Type 1A Receptor- and Insulin-Mediated Signaling Cross Talk Reviewed International journal

    Michihiro Hosojima, Hiroyoshi Sato, Keiko Yamamoto, Ryohei Kaseda, Taeko Soma, Asako Kobayashi, Akiyo Suzuki, Hideyuki Kabasawa, Aya Takeyama, Kenji Ikuyama, Noriaki Iino, Akira Nishiyama, Thomas J. Thekkumkara, Tetsuro Takeda, Yoshiki Suzuki, Fumitake Gejyo, Akihiko Saito

    ENDOCRINOLOGY   150 ( 2 )   871 - 878   2009.2

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    DOI： 10.1210/en.2008-0886

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  • Megalin-mediated endocytosis of cystatin C in proximal tubule cells Reviewed International journal

    Ryohei Kaseda, Noriaki Iino, Michihiro Hosojima, Tetsuro Takeda, Kiyoko Hosaka, Asako Kobayashi, Keiko Yamamoto, Akiyo Suzuki, Ayaka Kasai, Yoshiki Suzuki, Fumitake Gejyo, Akihiko Saito

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   357 ( 4 )   1130 - 1134   2007.6

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    DOI： 10.1016/j.bbrc.2007.04.072

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  • Functional characterization of a novel missense CLCN5 mutation causing alterations in proximal tubular endocytic machinery in Dent's disease Reviewed

    Atsuhito Tanuma, Hiroyoshi Sato, Tetsuro Takeda, Michihiro Hosojima, Hiroaki Obayashi, Hitomi Hama, Noriaki Iino, Kiyoko Hosaka, Ryohei Kaseda, Naofumi Imai, Mitsuhiro Ueno, Maya Yamazaki, Kenji Sakimura, Fumitake Gejyo, Akihiko Saito

    NEPHRON PHYSIOLOGY   107 ( 4 )   P87 - P97   2007

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    DOI： 10.1159/000111253

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  • Functional characterization of a novel missense CLCN5 mutation causing alterations in proximal tubular endocytic machinery in Dent's disease. Reviewed International journal

    Tanuma A, Sato H, Takeda T, Hosojima M, Obayashi H, Hama H, Iino N, Hosaka K, Kaseda R, Imai N, Ueno M, Yamazaki M, Sakimura K, Gejyo F, Saito A

    Nephron. Physiology   107 ( 4 )   p87 - 97   2007

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    BACKGROUND/AIMS: Mutations of the endosomal chloride/proton exchanger gene, CLCN5, cause Dent's disease, an X-linked recessive proximal tubular disorder. The renal endocytic system was found to be affected in clcn5 knockout mice. However, the impaired endocytic machinery of Dent's disease patients has not been thoroughly investigated. METHODS: The CLCN5 gene was sequenced in a Japanese patient with Dent's disease and his family. The loss-of-function phenotype of the missense CLCN5 mutation was investigated by gene expression in Xenopus oocytes and CHO cells. Immunohistochemical analysis was performed on kidney biopsy specimens for endocytic machinery proteins, megalin, cubilin, and disabled-2 (Dab2) in proximal tubules. RESULTS: Genomic analysis revealed a novel G-to-A transition at the first nucleotide of the 333rd codon of CLCN5, causing a substitution of glycine with arginine. Inefficient expression of the mutant gene in Xenopus oocytes resulted in abolished chloride currents. Impaired N-glycosylation of the mutant protein was evident in the DNA-transfected CHO cells. Proximal tubular expression of megalin, cubilin, and Dab2 was markedly reduced and irregular staining in some portions was observed in the patient compared with controls. CONCLUSIONS: A novel G333R CLCN5 mutation caused defective expression of megalin, cubilin, and Dab2 in a patient with Dent's disease.

    DOI： 10.1159/000111253

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Presentations

  • 食事療法の重要性～たんぱく質および食塩摂取量の管理を中心に～

    細島康宏, 蒲澤秀門, 鈴木芳樹, 斎藤亮彦, 成田一衛

    第34回日本糖尿病性腎症研究会 

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    Event date： 2023.12

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  • 糖尿病性腎症モデル動物を用いたSGLT2阻害薬使用時における尿中メガリン排泄量の推移

    細島康宏, 蒲澤秀門, 後藤佐和子, 竹本和矢, 小餅耕一, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第34回日本糖尿病性腎症研究会 

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    Event date： 2023.12

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  • Preliminary Open-Labeled Study to Examine the Effect of Cilastatin on the Pharmacokinetics of Cisplatin in Patients with Lung Cancer Undergoing Cisplatin-Based Chemotherapy

    Kabasawa H, Hosojima M, Goto S, Watanabe S, Tanaka T, Kitamura N, Narita I, Kikuchi T, Saito A

    American Society of Nephrology Kidney Week 2023 

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    Event date： 2023.11

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  • 原発性マクログロブリン血症に伴うメサンギウム増殖性腎炎にBTK阻害剤を導入した一例

    大塚忠司, 細島康宏, 山本卓, 成田一衛

    第53回日本腎臓学会東部学術大会 

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    Event date： 2023.9

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  • CKD診療の食事療法up to date ～低たんぱく質米の有用性～

    細島康宏

    第16回腎研究セミナー 

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    Event date： 2023.7

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  • 現時点において求められる透析患者の栄養課題に関する臨床研究 【学会委員会企画4 栄養問題検討ワーキンググループ企画 臨床研究から明らかになってきた透析患者の栄養課題】

    細島康宏, 蒲澤秀門, 村山稔子, 神田英一郎, 市川和子, 菅野義彦, 脇野修, 加藤明彦

    第68回日本透析医学会学術集会・総会 

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    Event date： 2023.6

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  • 透析セッション中の栄養補給 【ワークショップ8 透析患者の低栄養対策 Up To Date】

    細島康宏, 蒲澤秀門, 成田一衛

    第68回日本透析医学会学術集会・総会 

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    Event date： 2023.6

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  • 透析患者の甲状腺乳頭癌に対し，放射線ヨウ素内用療法を実施した経験例

    渡邉和樹, 後藤佐和子, 渡辺博文, 細島康宏, 山本卓, 野林大幹, 飯田倫理, 青柳竜治, 海津元樹, 成田一衛

    第68回日本透析医学会学術集会・総会 

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    Event date： 2023.6

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  • 十分なタンパク摂取量とリン過剰負荷のジレンマをどう解決するか？ 【ワークショップ22 透析療法における腎臓リハビリと栄養管理】

    蒲澤秀門, 細島康宏, 成田一衛

    第68回日本透析医学会学術集会・総会 

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    Event date： 2023.6

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  • たんぱく質の質～食事パターンも含めて～ 【シンポジウム3 末期腎不全患者における新しい栄養管理】

    佐藤弘恵, 細島康宏, 鈴木芳樹, 成田一衛

    第68回日本透析医学会学術集会・総会 

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    Event date： 2023.6

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  • 透析時静脈栄養(Intradialytic parenteral nutrition: IDPN)の今後 【シンポジウム3 末期腎不全患者における新しい栄養管理】

    蒲澤秀門, 細島康宏, 成田一衛

    第68回日本透析医学会学術集会・総会 

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    Event date： 2023.6

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  • SGLT2阻害薬使用時におけるメガリンおよびメガリンリガンドの尿中排泄量の推移

    細島康宏, 蒲澤秀門, 田中崇裕, 北村信隆, 後藤佐和子, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第66回日本腎臓学会学術総会  2023.6 

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  • 代謝性アシドーシスと食事性酸負荷 【学会主導企画2「CKDガイドラインが導く新しい電解質管理2023」】

    細島康宏, 蒲澤秀門, 成田一衛

    第66回日本腎臓学会学術総会 

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    Event date： 2023.6

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  • 3カ月間の生活習慣改善が血清レプチンとアルブミン尿に与える影響―肥満の効果修飾について―

    蒲澤佳子, 細島康宏, 伊藤由美, 成田一衛, 斎藤亮彦

    第66回日本腎臓学会学術総会 

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    Event date： 2023.6

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  • シスプラチンを含むがん化学療法におけるシラスタチンの急性腎障害予防効果を検討するための薬物動態試験

    蒲澤秀門, 細島康宏, 後藤佐和子, 田中崇裕, 北村信隆, 成田一衛, 斎藤亮彦

    第66回日本腎臓学会学術総会 

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    Event date： 2023.6

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  • メガリンが関与する造影剤腎症の発症メカニズムの解明とその予防法の開発

    後藤佐和子, 細島康宏, 蒲澤秀門, 忰田亮平, 成田一衛, 斎藤亮彦

    第66回日本腎臓学会学術総会 

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    Event date： 2023.6

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  • BTK阻害剤により腎機能が改善した原発性マクログロブリン血症の1例

    藤澤智彦, 大塚忠司, 藤井美里, 褚瑰麗, 細島康宏, 成田一衛

    第152回日本内科学会信越地方会 

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    Event date： 2023.5

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  • CKDの食事療法における低たんぱく質ご飯の有用性 【シンポジウム13 臨床現場における糖尿病性腎症のマネージメント】

    細島康宏, 蒲澤秀門, 鈴木芳樹, 斎藤亮彦, 成田一衛

    第66回日本糖尿病学会年次学術集会 

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    Event date： 2023.5

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  • SGLT2阻害薬使用時における尿中メガリンおよびメガリンリガンド分子の動態

    細島康宏, 蒲澤秀門, 田中崇裕, 北村信隆, 後藤佐和子, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第66回日本糖尿病学会年次学術集会 

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    Event date： 2023.5

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  • 甲状腺乳頭癌に対して、放射性ヨウ素内用療法を実施した維持透析患者の一例

    渡邉和樹, 後藤佐和子, 渡辺博文, 細島康宏, 山本卓, 成田一衛, 野林大幹, 飯田倫理, 青柳竜治, 海津元樹

    第56回新潟透析医学会学術集会 

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    Event date： 2023.4

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  • 血液透析中の食事摂取状況と新型コロナウイルス感染症（COVID-19）流行の影響に関する連続横断研究

    蒲澤秀門, 細島康宏, 斎藤亮彦, 鈴木芳樹, 成田一衛

    第56回新潟透析医学会学術集会 

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    Event date： 2023.4

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  • 糖尿病性腎症重症化予防事業での地域特性による塩分チェックシートを使用した減塩指導の効果

    村山稔子, 細島康宏, 蒲澤秀門, 伊藤愛奈, 小林美聡, 上法花子, 増岡里紗, 久志田順子, 山田恭子, 澤田香織, 志賀久美子, 斎藤亮彦, 鈴木芳樹, 成田一衛

    第13回日本腎臓リハビリテーション学会学術集会 

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    Event date： 2023.3

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  • 食事調査との比較における新規栄養関連マーカーNRI-JHの評価

    小嶋準一, 細島康宏, 蒲澤秀門, 成田一衛

    第13回日本腎臓リハビリテーション学会学術集会 

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    Event date： 2023.3

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  • 糖尿病透析患者の栄養管理 【シンポジウム2 次世代に繋げるCKDに伴う糖尿病管理】

    細島康宏, 蒲澤秀門, 成田一衛

    第2回日本腎不全合併症医学会学術集会・総会 

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    Event date： 2023.2

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  • 2型糖尿病を合併した維持血液透析患者におけるグルカゴン測定法の比較検討

    吉澤優太, 細島康宏, 蒲澤秀門, 田邊直仁, 宮地淳, 浜島斉, 三重野園理, 小林雅樹, 北村忠弘, 成田一衛, 斎藤亮彦

    第49回新潟糖尿病談話会 

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    Event date： 2023.2

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  • ステロイド糖尿病の経過中、両大腿の違和感で発症した両側非定型大腿骨不全骨折の一例

    渡邉和樹, 黒澤陽一, 長谷川絵理子, 若松彩子, 蒲澤秀門, 細島康宏, 佐藤弘恵, 中枝武司, 鈴木芳樹, 斎藤亮彦, 成田一衛

    第49回新潟糖尿病談話会 

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    Event date： 2023.2

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  • 糖尿病性腎症重症化予防における地域特性に基づく塩分チェックシートを使用した指導効果について

    村山稔子, 細島康宏, 蒲澤秀門, 伊藤愛奈, 小林美聡, 上法花子, 増岡里紗, 久保田順子, 山田恭子, 澤田香織, 志賀久美子, 斎藤亮彦, 鈴木芳樹, 成田一衛

    第49回新潟糖尿病談話会 

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    Event date： 2023.2

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  • 2型糖尿病における腎予後予測のための尿中メガリン測定の意義

    飯田倫理, 細島康宏, 蒲澤秀門, 蒲澤佳子, 後藤佐和子, 田中崇裕, 北村信隆, 小笠原真也, 忰田亮平, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第49回新潟糖尿病談話会 

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    Event date： 2023.2

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  • ステロイド糖尿病の経過中に両側非定型大腿骨不全骨折を生じた一例

    渡邉和樹, 黒澤陽一, 長谷川絵理子, 若松彩子, 蒲澤秀門, 細島康宏, 佐藤弘恵, 中枝武司, 鈴木芳樹, 斎藤亮彦, 成田一衛

    第60回日本糖尿病学会関東甲信越地方会 

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    Event date： 2023.1

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  • CKD患者の栄養管理Up to date～カリウム管理の重要性も含めて～ 【共催セミナー7】

    細島康宏

    第26回日本病態栄養学会年次学術集会 

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    Event date： 2023.1

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  • Pros：SGLT2免疫阻害薬は栄養学的に良いのか、悪いのか～是の立場から～ 【コントラバーシー2 SGLT2免疫阻害薬は栄養学的に良いのか、悪いのか】

    細島康宏

    第26回日本病態栄養学会年次学術集会 

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    Event date： 2023.1

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  • 米たんぱく質および食事性酸負荷が腎臓に与える影響について～日本食パターンへの期待を込めて～ 【シンポジウム5 食を科学する】

    細島康宏

    第26回日本病態栄養学会年次学術集会 

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    Event date： 2023.1

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  • 血液透析中の食事摂取状況と新型コロナウイルス感染症(COVID-19)流行の影響に関する連続横断研究

    蒲澤秀門, 細島康宏, 斎藤亮彦, 鈴木芳樹, 成田一衛

    第26回日本病態栄養学会年次学術集会 

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    Event date： 2023.1

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  • SGLT2阻害薬使用時における尿中メガリンおよびメガリンリガンド分子の動態

    細島康宏, 蒲澤秀門, 後藤佐和子, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第33回日本糖尿病性腎症研究会 

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    Event date： 2022.12

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  • 糖尿病性腎症重症化予防事業における地域特性に基づく塩分チェックシートを使用した指導効果について

    村山稔子, 細島康宏, 蒲澤秀門, 久志田順子, 山田恭子, 澤田香織, 志賀久美子, 斎藤亮彦, 鈴木芳樹, 成田一衛

    第33回日本糖尿病性腎症研究会 

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    Event date： 2022.12

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  • Rothmund-Thomson 症候群に合併した特発性多中心性Castleman病(iMCD)の1例

    米沢正貴, 後藤佐和子, 後藤慧, 蒲澤秀門, 細島康宏, 今井直史, 伊藤由美, 成田一衛, 正木康史

    第52回日本腎臓学会東部学術大会 

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    Event date： 2022.10

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  • 基本をおさえた保存期CKDの栄養管理【教育講演22栄養管理の理論と実践】

    細島康宏, 蒲澤秀門

    第67回日本透析医学会学術集会・総会 

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    Event date： 2022.7

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  • 透析患者の脳血管障害 脳卒中急性期の透析管理の工夫【シンポジウム5<合併症の予防・管理のSDGsを求めて>】

    蒲澤秀門, 細島康宏, 成田一衛

    第67回日本透析医学会学術集会・総会 オンライン・神奈川県 横浜市 

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    Event date： 2022.7

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  • 2022年における栄養とCKD【ランチョンセミナー37食事療法】

    細島康宏

    第67回日本透析医学会学術集会・総会 

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    Event date： 2022.7

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  • 溶血関連腎症におけるメガリンの役割とのその治療戦略

    後藤佐和子, 細島康宏, 蒲澤秀門, 成田一衛, 斎藤亮彦

    第65回日本腎臓学会学術総会 

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    Event date： 2022.6

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  • 2型糖尿病患者における尿中メガリン測定による腎予後予測

    飯田倫理, 細島康宏, 蒲澤秀門, 蒲澤佳子, 後藤佐和子, 田中崇裕, 北村信隆, 忰田亮平, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第65回日本腎臓学会学術総会 

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    Event date： 2022.6

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  • エクソーム解析により新規異変を同定したAlport症候群と家族性若年糖尿病の一家系

    渡辺博文, 後藤眞, 細島康宏, 成田一衛

    第65回日本腎臓学会学術総会 

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    Event date： 2022.6

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  • 重軽鎖アミロイドーシスと診断したネフローゼ症候群の1例

    入沢大喜, 米沢正貴, 後藤慧, 蒲澤秀門, 細島康宏, 伊藤由美, 金子佳賢, 成田一衛, 片桐隆幸, 瀧澤淳

    日本内科学会信越支部主催 第150回信越地方会 

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    Event date： 2022.6

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  • 血液透析患者におけるIDPNの現状と課題 【ワークショップ09「血液浄化療法下での栄養療法のニューノーマル」】

    細島康宏

    第37回日本臨床栄養代謝学会学術集会 

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    Event date： 2022.5 - 2022.6

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  • 低栄養の維持血液透析患者における一般用アミノ酸輸液製剤エネフリードを用いた透析時静脈栄養に関する検討

    細島康宏, 蒲澤秀門, 保川亮太, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第64回新潟透析医学会学術集会 

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    Event date： 2022.5

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  • 血液透析中の食事摂取状況とコロナ禍による影響～新潟透析医学会参加施設へのアンケート調査～

    蒲澤秀門, 細島康宏, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第64回新潟透析医学会学術集会 

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    Event date： 2022.5

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  • 2型糖尿病患者における尿中メガリンの腎予後予測能の検討

    飯田倫理, 細島康宏, 蒲澤秀門, 蒲澤佳子, 後藤佐和子, 田中崇裕, 北村信隆, 忰田亮平, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第65回日本糖尿病学会年次学術集会 

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    Event date： 2022.5

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  • サルコペニア・フレイルを考慮したCKDの栄養【シンポジウム】

    細島康宏, 蒲澤秀門, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第12回日本腎臓リハビリテーション学会学術集会 

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    Event date： 2022.3

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  • 腎移植患者における食事療法の実際【ジョイントシンポジウム】

    細島康宏, 蒲澤秀門, 鈴木芳樹, 斎藤亮彦, 成田一衛

    第12回日本腎臓リハビリテーション学会学術集会 

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    Event date： 2022.3

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  • 低栄養の維持血液透析患者におけるエネフリード輸液を用いた透析時静脈栄養に関する検討

    松永麻衣, 細島康宏, 蒲澤秀門, 保川亮太, 鈴木芳樹, 斎藤亮彦, 成田一衛

    第12回日本腎臓リハビリテーション学会学術集会 

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    Event date： 2022.3

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  • エンパグリフロジン投与開始後の食事摂取状況の変化とHbA1cおよび体重の変化との関連

    村山稔子, 細島康宏, 蒲澤秀門, 田中崇裕, 北村信隆, 桑原頌治, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第12回日本腎臓リハビリテーション学会学術集会 

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    Event date： 2022.3

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  • CKD患者の栄養管理Up to data～カリウムの話題も含めて～【共催セミナー12】

    細島康宏

    第24・25回日本病態栄養学会年次学術集会 

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    Event date： 2022.1

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  • サルコペニア・フレイルを考慮したCKDの食事療法について 【合同パネルディスカッション3 日本サルコペニア・フレイル学会 CKDにおけるサルコペニア・フレイルの栄養管理】

    細島康宏

    第24・25回日本病態栄養学会年次学術集会 

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    Event date： 2022.1

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  • 境界型糖尿病と高血圧の合併例に結節性糸球体病変が認められた一例

    山口浩毅, 細島康宏, 蒲澤秀門, 後藤佐和子, 伊藤由美, 今井直史, 鈴木芳樹, 斎藤亮彦, 成田一衛

    第32回日本糖尿病性腎症研究会 

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    Event date： 2021.12

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  • 骨髄移植後の慢性GVHDに伴う膜性腎症の一例

    齋藤耕吉, 後藤佐和子, 後藤慧, 蒲澤秀門, 細島康宏, 伊藤由美, 金子佳賢, 成田一衛

    第149回日本内科学会信越地方会 

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    Event date： 2021.10

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  • 高齢者のCKD・CKD診療の現状【シンポジウム8「CKD・DKD診療の新展開」】

    細島康宏, 蒲澤秀門, 鈴木芳樹, 斎藤亮彦, 成田一衛

    第51回日本腎臓学会東部学術大会 

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    Event date： 2021.9

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  • 慢性腎臓病に対する栄養指導～2021年の日本におけるその実際と実践について～

    細島康宏

    2021年度全国栄養士大会 

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    Event date： 2021.8

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  • 透析患者の栄養補給(IDPNも含めて)

    細島康宏

    第9回日本腎栄養代謝研究会学術集会・総会 

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    Event date： 2021.7

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  • CKD診療ガイドラインに基づく低たんぱく食の有効性【抗加齢栄養療法指導講習会 テーマ「CKD患者の栄養療法，特にたんぱく質制限の取り扱い」】

    細島康宏

    第21回日本抗加齢医学会総会 

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    Event date： 2021.6

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  • 進行期CKD患者における栄養指導の実態(横断研究)～REACH-J-CKDコホート研究より～

    細島康宏, 蒲澤秀門, 村山稔子, 若杉美奈子, 鈴木芳樹, 斎藤亮彦, 岡田浩一, 和田隆志, 山縣邦弘, 柏原直樹, 成田一衛

    第64回日本腎臓学会学術総会 

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    Event date： 2021.6

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  • 維持血液透析患者における透析時静脈栄養（IDPN）の実態

    細島康宏, 蒲澤秀門, 鈴木芳樹, 斎藤亮彦, 成田一衛

    第66回日本透析医学会学術集会・総会 

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    Event date： 2021.6

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  • 2021年における栄養とCKD 【ランチョンセミナー31】

    細島康宏

    第66回日本透析医学会学術集会・総会 

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    Event date： 2021.6

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  • 2型糖尿病患者におけるCOVID-19の流行が食事習慣に及ぼす影響に関する自記式食事歴法質問票（GHQ）を用いた検討

    蒲澤秀門, 細島康宏, 村山稔子, 桑原頌治, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第64回日本糖尿病学会年次学術集会 

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    Event date： 2021.5

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  • 腎臓リハビリテーションにおける食事療法の位置づけとエビデンス

    細島康宏, 蒲澤秀門, 成田一衛

    第11回日本腎臓リハビリテーション学会学術集会 

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    Event date： 2021.3

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  • 糸球体結節性病変と係蹄壁へのIgG線状沈着を呈した境界型糖尿病の1例

    山口浩毅, 細島康宏, 蒲澤秀門, 後藤佐和子, 後藤慧, 伊藤由美, 今井直史, 金子佳賢, 鈴木芳樹, 斎藤亮彦, 成田一衛

    第58回日本糖尿病学会関東甲信越地方会 

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    Event date： 2021.1

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  • 腹膜透析に関連した非結核性抗酸菌症によるカテーテル関連感染症および腹膜炎の一例

    植木亮太郎, 伊藤徹, 須藤真則, 後藤佐和子, 後藤慧, 酒巻裕一, 細島康宏, 金子佳賢, 成田一衛

    第62回新潟透析医学会学術集会 

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    Event date： 2020.11

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  • 無尿で血液透析導入後に腎生検を施行し、微小変化型ネフローゼ症候群と診断した高齢者の一例

    伊藤徹, 須藤真則, 後藤佐和子, 後藤慧, 伊藤由美, 細島康宏, 佐藤信之, 金子佳賢, 成田一衛

    第62回新潟透析医学会学術集会 

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    Event date： 2020.11

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  • 尿毒症毒素と栄養【シンポジウム8「透析患者の低栄養対策」】

    細島康宏

    第65回日本透析医学会学術集会・総会 

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    Event date： 2020.11

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  • 透析患者に対する静脈栄養剤・経腸栄養剤による低栄養の改善について

    細島康宏, 蒲澤秀門, 成田一衛

    第65回日本透析医学会学術集会・総会 

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    Event date： 2020.11

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  • インスリン使用中の維持血液透析患者におけるデュラグルチド併用による血糖管理の有効性およびQOL改善に関する探索的臨床試験

    宇賀村大亮, 細島康宏, 蒲澤秀門, 田邊直仁, 吉澤優太, 忰田亮平, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第63回日本糖尿病学会年次学術集会 

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    Event date： 2020.10

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  • 腹膜透析カテーテル抜去後も非結核性抗酸菌による難治性の皮下感染が遷延した一例

    伊藤徹, 後藤佐和子, 後藤慧, 細島康宏, 金子佳賢, 成田一衛

    第50回 日本腎臓学会東部学術大会 

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    Event date： 2020.9

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  • マウス尿中メガリン測定用サンドイッチELISAの開発とその応用

    早福莉那, 後藤佐和子, 細島康宏, 蒲澤秀門, 忰田亮平, 成田一衛, 斎藤亮彦

    第63回日本腎臓学会学術集会 

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    Event date： 2020.8

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  • 抗リボソームP抗体とループス腎炎の長期腎予後との関連について

    佐藤弘恵, 若松彩子, 張高正, 須藤真則, 長谷川絵理子, 細島康宏, 小林大介, 中枝武司, 金子佳賢, 成田一衛

    第63回日本腎臓学会学術集会 

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    Event date： 2020.8

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  • CKD，DKD患者への食事療法：腎臓専門医の立場から(たんぱく質制限効果も含め)【シンポジウム11 DKDと食事 Up to date】

    細島康宏

    第63回日本腎臓学会学術集会 

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    Event date： 2020.8

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  • メガリンを介する腎内レニン-アンジオテンシン(Ang)系(RAS)の動的均衡化制御機構

    後藤佐和子, 吉田豊, 細島康宏, 蒲澤秀門, 忰田亮平, 成田一衛, 斎藤亮彦

    第63回日本腎臓学会学術集会 

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    Event date： 2020.8

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  • 高齢者CKD患者における低たんぱく食～是の立場からの考察～【コントラバシー1 高齢CKD患者に対して 低たんぱく食は是か非か～治療効果と低栄養のはざまで～】

    細島康宏

    第23回日本病態栄養学会年次学術集会 

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    Event date： 2020.1

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  • メタボリックシンドロームと尿マーカーの関連：特にA-メガリンについて

    蒲澤佳子, 細島康宏, 伊藤由美, 蒲澤秀門, 黒澤寛之, 平山吉朗, 中村和利, 松島一雄, 成田一衛, 斎藤亮彦

    第31回日本糖尿病性腎症研究会 

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    Event date： 2019.11 - 2019.12

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  • インスリン使用中の2型糖尿病維持血液透析患者におけるデュラグルチド併用の有用性に関する検討

    宇賀村大亮, 細島康宏, 蒲澤秀門, 田邊直仁, 吉澤優太, 忰田亮平, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第31回日本糖尿病性腎症研究会 

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    Event date： 2019.11 - 2019.12

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  • 2型糖尿病合併の有無がCKD患者の低たんぱく質食事療法に与える影響に関する検討

    蒲澤秀門, 細島康宏, 忰田亮平, 田中友美, 樋口裕樹, 村山稔子, 桑原頌治, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第31回日本糖尿病性腎症研究会 

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    Event date： 2019.11 - 2019.12

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  • 幼少期における米胚乳タンパク質の摂取が成熟期の高脂肪食負荷による肥満および肥満関連腎症に及ぼす影響

    樋口裕樹, 細島康宏, 蒲澤秀門, 桑原頌治, 後藤佐和子, 忰田亮平, 伊藤彰, 荒生均, 成田一衛, 斎藤亮彦

    第31回日本糖尿病性腎症研究会 

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    Event date： 2019.11 - 2019.12

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  • 2型糖尿病を合併した維持血液透析患者におけるグルカゴン測定法に関する比較検討

    吉澤優太, 細島康宏, 蒲澤秀門, 田邊直仁, 鈴木芳樹, 宮地淳, 浜島斉, 小林雅樹, 北村忠弘, 成田一衛, 斎藤亮彦

    第31回日本糖尿病性腎症研究会 

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    Event date： 2019.11 - 2019.12

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  • Acute Tubulointerstitial Nephritis Associated with a Vaccination of Japanese Encephalitis Virus: A Case Study.

    Nakano K, Iida T, Hosojima M, Chu G, Hosaka K, Ito Y, Yamamoto S, Goto S, Narita I

    American Society of Nephrology 51th Annual Meeting. 

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    Event date： 2019.11

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  • An Exploratory Clinical Trial on the Efficacy and Safety of the GLP-1 Receptor Agonist Dulaglutide in Patients with Type 2 Diabetes Mellitus on Maintenance Hemodialysis

    Ugamura D, Hosojima M, Kabasawa H, Tanabe N, Yoshizawa Y, Kaseda R, Kono E, Takeyama A, Miura T, Fujikawa H, Yamazaki H, Sasage H, Aoike I, Miura Y, Suzuki Y, Narita I, Saito A

    American Society of Nephrology 51th Annual Meeting. 

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    Event date： 2019.11

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  • Association Between Urinary A Megalin and Metabolic Syndrome in Japanese Adults.

    Kabasawa K, Hosojima M, Ito Y, Kurosawa H, Kabasawa H, Hirayama Y, Nakamura K, Saito A, Matsushima K, Tanaka J, Narita I

    American Society of Nephrology 51th Annual Meeting. 

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    Event date： 2019.11

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  • 2型糖尿病を有する維持血液透析患者におけるオマリグリプチンの有用性の検討

    吉澤優太, 細島康宏, 蒲澤秀門, 田邊直仁, 甲田豊, 島田久基, 高澤哲也, 伊藤孝仁, 北村忠弘, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第64回日本透析医学会学術集会 

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  • 透析症例におけるサキサクリプチンの有用性について

    青池郁夫, 細島康宏, 宇賀村大亮

    第64回日本透析医学会学術集会 

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  • カフ型カテーテルが長期使用後に抜去困難となった一例

    中野惠輔, 飯田倫理, 細島康宏, 保坂聖子, 山本卓, 後藤眞, 成田一衛

    第64回日本透析医学会学術集会 

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  • 一般地域住民における食事性酸負荷とアルブミン尿の関連

    蒲澤佳子, 細島康宏, 伊藤由美, 中村和利, 斎藤亮彦, 成田一衛

    第62回日本腎臓学会学術集会 

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  • 2型糖尿病を合併した維持血液透析患者におけるグルカゴン測定法の検討

    吉澤優太, 細島康宏, 蒲澤秀門, 田邊直仁, 甲田豊, 島田久基, 髙澤哲也, 伊藤孝仁, 鈴木芳樹, 宮地淳, 浜島斉, 小林雅樹, 北村忠弘, 成田一衛, 斎藤亮彦

    第62回日本腎臓学会学術集会 

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  • メガリンを介した抗癌化学療法による腎障害の対策

    蒲澤秀門, 細島康宏, 後藤佐和子, 忰田亮平, 斎藤亮彦, 成田一衛

    第62回日本腎臓学会学術集会 

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  • メタボリックシンドロームと尿バイオマーカーの関連について

    蒲澤佳子, 細島康宏, 伊藤由美, 黒澤寛之, 平山吉朗, 斎藤亮彦, 成田一衛

    第62回日本腎臓学会学術集会 

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  • Rice endosperm protein intake in childhood suppresses the development of high-fat diet-induced metabolic disorders and kidney disease in adulthood in mice

    Higuchi Y, Hosojima M, Kabasawa H, Kuwahara S, Kaseda R, Arao H, Narita I, Saito A

    American Diabetes Association 79th scientific sessions 

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  • A Multicenter, Randomized, Controlled Study of the Efficacy of Once-Weekly DPP-4 Inhibitor Omarigliptin in Patients with Type 2 Diabetes Undergoing Maintenance Hemodialysis

    Yoshizawa Y, Hosojima M, Kabasawa H, Tanabe N, Kitamura T, Narita I, Saito A

    American Diabetes Association 79th scientific sessions 

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  • 自記式食事歴質問票(DHQ)を用いたSGLT2阻害薬の効果と食事摂取状況の検討

    村山稔子, 細島康宏, 蒲澤秀門, 桑原頌治, 田中崇裕, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第62回日本糖尿病学会年次学術集会 

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  • インスリン投与中の維持血液透析患者におけるデュラグルチド追加投与の2自験例～看護面からの考察～

    大瀧由布子, 塚野裕美, 岩間麻美, 後藤薫, 知野由利子, 倉田昌代, 宇賀村大亮, 細島康宏, 蒲澤秀門, 成田一衛, 斎藤亮彦, 藤川浩一

    第61回新潟透析医学会学術集会 

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  • 長期使用したカフ型カテーテルが抜去困難となった二例

    高村紗由里, 飯田倫理, 細島康宏, 保坂聖子, 山本卓, 後藤眞, 津畑豊, 霜鳥正明, 小林英之, 成田一衛

    第61回新潟透析医学会学術集会 

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  • 嚥下困難で発症した頭蓋底骨髄炎を合併した維持血液透析患者の一例

    佐藤聡磨, 後藤佐和子, 飯田倫理, 細島康宏, 保坂聖子, 山本卓, 後藤眞, 高橋邦行, 成田一衛

    第61回新潟透析医学会学術集会 

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  • 新潟大学および新潟県における平成30年の腎移植・膵腎移植と臓器提供

    斎藤和英, 田崎正行, 池田正博, 冨田善彦, 伊藤由美, 今井直史, 細島康宏, 山本卓, 成田一衛, 小林隆, 三浦宏平, 若井俊文, 秋山政

    第61回新潟透析医学会学術集会 

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  • 維持血液透析患者におけるグルカゴン測定法の比較検討

    吉澤優太, 細島康宏, 蒲澤秀門, 田邉直仁, 甲田豊, 島田久基, 髙澤哲也, 伊藤孝仁, 鈴木芳樹, 宮地淳, 浜島斉, 小林雅樹, 北村忠弘, 成田一衛, 斎藤亮彦

    第61回新潟透析医学会学術集会 

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  • インスリン使用中の維持血液透析患者におけるGLP-1受容体作動薬デュラグルチド併用の有効性および安全性に関する探査的臨床試験

    宇賀村大亮, 細島康宏, 蒲澤秀門, 田邊直仁, 吉澤優太, 忰田亮平, 河野恵美子, 竹山綾, 三浦隆義, 藤川浩一, 須貝昌博, 山崎肇, 捧博輝, 青池郁夫, 三浦義明, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第61回新潟透析医学会学術集会 

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  • 低たんぱく質米の使用がCKD患者のたんぱく質摂取量に与える効果に関する他施設共同無作為化比較試験

    細島康宏, 蒲澤秀門, 忰田亮平, 田中友美, 小尾佳嗣, 樋口裕樹, 村山稔子, 桑原頌治, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第9回日本腎臓リハビリテーション学会学術集会 

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    Event date： 2019.3

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  • 2型糖尿病を合併した維持血液透析患者におけるオマリグリプチンの有用性の検討

    吉澤優太, 細島康宏, 蒲澤秀門, 田邊直仁, 甲田豊, 島田久基, 高澤哲也, 伊藤孝仁, 鈴木芳樹, 成田一衛, 斎藤亮彦

    日本糖尿病学会 第56回関東甲信越地方会 

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    Event date： 2019.1

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  • 低たんぱく質米の使用がCKD患者のたんぱく質摂取量に与える効果に関する他施設共同無作為化比較試験

    細島康宏, 蒲澤秀門, 忰田亮平, 田中友美, 小尾佳嗣, 樋口裕樹, 村山稔子, 桑原頌治, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第22回日本病態栄養学会年次学術集会 

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  • 2型糖尿病合併血液透析患者のCGMによる血糖変動と低血糖の評価：DPP-4阻害薬の血糖変動幅縮小効果の可能性

    石川友美, 細島康宏, 忰田亮平, 蒲澤秀門, 桑原頌治, 飯野則昭, 田中崇裕, 北村信隆, 鈴木芳樹, 斎藤亮彦, 成田一衛

    第29回 日本糖尿病性腎症研究会  2018.12 

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  • 自己末梢血管細胞移植後に血栓性微小血管症(TMA)による腎障害を合併した一例

    白柏由佳, 後藤佐和子, 細島康宏, 保坂聖子, 山本卓, 今井直史, 伊藤由美, 後藤眞, 成田一衛

    第48回日本腎臓学会東部学術集会  2018.10 

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  • 本院における低たんぱく質米を使用した腎臓病教室食事会の取り組み

    小師優子, 村山稔子, 蒲澤秀門, 細島康宏

    第65回日本栄養改善学会学術総会  2018.9 

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  • 美味しく、治す治療食～腎臓を守る食事とは～

    細島 康宏

    第61回日本腎臓学会学術総会 市民公開講座  2018.6 

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  • ボルマブ治療終了後に難治浮腫を発症した進行期肺癌の1例

    小山健一, 青木亜美, 野嵜幸一郎, 三浦理, 田中洋史, 細島康宏, 保坂聖子, 山本卓, 成田一衛

    第142回信越地方会  2018.6 

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  • 血液透析中における栄養補助療法

    細島康宏, 蒲澤秀門, 斎藤亮彦

    第63回日本透析医学会学術集会・総会  2018.6 

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  • CKDにおける治療用特殊食品の有用性

    村山稔子, 細島康宏, 蒲澤秀門, 鈴木芳樹, 斎藤亮彦, 成田一衛

    第61回日本腎臓学会学術総会  2018.6 

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  • 食事性酸負荷とCKDの進行との関連

    蒲澤秀門, 細島康宏, 村山稔子, 鈴木芳樹, 斎藤亮彦, 成田一衛

    第61回日本腎臓学会学術総会  2018.6 

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  • 糖尿病性腎臓病に対する摂取たんぱく質の違いによる「腸-腎関連」を介した発症・進展機序の解明

    細島康宏, 樋口裕樹, 蒲澤秀門, 桑原頌治, 成田一衛, 斎藤亮彦

    第61回日本腎臓学会学術総会  2018.6 

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  • 低たんぱく質米の使用がCKD患者におけるたんぱく質摂取量に与える効果に関する多施設共同無作為化比較試験

    細島康宏, 蒲澤秀門, 忰田亮平, 石川友美, 小尾佳嗣, 樋口裕樹, 村山稔子, 桑原頌治, 鈴木芳樹, 斎藤亮彦, 成田一衛

    第61回日本腎臓学会学術総会  2018.6 

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  • 尿中A-メガリンはシスプラチン腎症の発症予測マーカーとなりうる

    蒲澤秀門, 飯田倫理, 細島康宏, 桑原頌治, 成田一衛, 斎藤亮彦

    第61回日本腎臓学会学術総会  2018.6 

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  • 12週間の生活習慣改善プログラムの腎障害に与える影響

    蒲澤佳子, 細島康宏, 成田一衛, 斎藤亮彦, 荒川正昭

    第61回日本腎臓学会学術総会  2018.6 

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  • 2型糖尿病を合併した腎移植後患者におけるSGLT2阻害薬の使用経験

    蒲澤秀門, 細島康宏, 亀田茂美, 宇賀村大亮, 吉澤優太, 飯田倫理, 後藤佐和子, 忰田亮平, 保坂聖子, 成田一衛, 鈴木芳樹, 斎藤亮彦

    第60回新潟透析医学会学術集会  2018.5 

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  • 食事はどうしたらよいでしょうか？

    細島 康宏

    第29回日本糖尿病性腎症研究会 新潟サテライト市民公開講演会  2018.4 

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  • Rice endosperm protein intake in childhood suppresses the development of high-fat diet-induced metabolic disorders and kidney disease in adulthood in mice International conference

    Higuchi Y, Hosojima M, Kabasawa H, Kuwahara S, Kaseda R, Maruyama K, Narita I, Saito A

    ISN FRONTIERS MEETINGS 2018  2018.2 

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  • Sodium glucose transporter 2 inhibition with dapagliflozin downregulates megalin expression in proximal tubule epithelial cells. International conference

    Iida T, Kuwahara S, Hosojima M, Ishikawa T, Goto S, Kabasawa H, Kaseda R, Suzuki Y, Narita I, Saito A

    ISN FRONTIERS MEETINGS 2018  2018.2 

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  • Plant protein compared to animal protein improves anti-inflammatory effects of HDL and lessens CKD-induced atherosclerosis International conference

    Kaseda R, Hosojima M, Kuwahara S, Kabasawa H, Aoki H, Higuchi Y, Kon V, Maruyama K, Narita I, Saito A

    ISN FRONTIERS MEETINGS 2018  2018.2 

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  • Higher estimated net endogenous acid production with lower intake of fruits and vegetables is associated with the progression of chronic kidney disease in Japan International conference

    Kabasawa H, Hosojima M, Toba K, Kuwahara S, Tanabe N, Kaseda R, Suzuki Y, Narita I, Saito A

    ISN FRONTIERS MEETINGS 2018  2018.2 

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  • Effectiveness of DPP-4inhibitors for blood glucose variability in type 2 diabetes patients undergoing maintenance hemodialysis International conference

    Ishikawa T, Hosojima M, Kabasawa H, Kaseda R, Kuwahara S, Iino N, Tanaka T, Kitamura N, Suzuki Y, Narita I, Saito A

    ISN FRONTIERS MEETINGS 2018  2018.2 

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  • Two forms of urinary megalin excretion are novel predictors of the progression of early-stage diabetic kidney disease in type 2 diabetes International conference

    Iida T, Hosojima M, Kabasawa K, Nakamura K, Kuwahara S, Ishikawa T, Kaseda R, Kurosawa H, Hirayama Y, Narita I, Saito A

    ISN FRONTIERS MEETINGS 2018  2018.2 

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  • 美味しく、治す治療食～腎臓を守る食事とは～

    細島 康宏

    市民公開講座 生活習慣を見直して守ろう腎臓！  2018.1 

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  • 代謝性アシドーシスと栄養

    村山稔子, 細島康宏, 鳥羽宏司, 蒲澤秀門, 桑原頌治, 忰田亮平, 石川友美, 和田恵梨, 渡邊令子, 田邊直仁, 成田一衛, 鈴木芳樹, 斎藤芳樹

    第21回日本病態栄養学会年次学術集会  2018.1 

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  • 第29回 日本糖尿病性腎症研究会

    蒲澤秀門, 細島康宏, 羽深将人, 山本卓, 後藤眞, 鈴木芳樹, 斎藤亮彦, 成田一衛

    第29回 日本糖尿病性腎症研究会  2017.12 

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  • 新潟県燕市における糖尿病性腎症重症化予防における取り組み

    細島康宏, 蒲澤秀門, 本間修, 甲田豊, 原田隆, 斎藤亮彦, 鈴木芳樹, 成田一衛

    第29回 日本糖尿病性腎症研究会  2017.12 

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  • 新潟市の糖尿病性腎症重症化予防事業における栄養指導プログラムの構築について

    村山稔子, 細島康宏, 牧野令子, 佐藤純子, 水野佐智子, 蒲澤秀門, 斎藤亮彦, 鈴木芳樹, 成田一衛

    第29回 日本糖尿病性腎症研究会  2017.12 

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  • Nrf活性化薬バルドキソロンメチルによる近位尿細管細胞のメガリン発現抑制機序の解析

    桑原頌治, 細島康宏, 蒲澤秀門, 忰田亮平, 宇賀村大亮, 吉澤優太, 後藤佐和子, 飯田倫理, 成田一衛, 斎藤亮彦

    第29回 日本糖尿病性腎症研究会  2017.12 

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  • 近位尿細管におけるSGLT2阻害薬ダパグリフロジンのメガリン発現抑制作用

    飯田倫理, 桑原頌治, 細島康宏, 石川友美, 後藤佐和子, 蒲澤秀門, 忰田亮平, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第29回 日本糖尿病性腎症研究会  2017.12 

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  • 慢性腎臓病における低たんぱく質米飯を使用した食事療法の可能性～産官学連携による臨床研究～

    細島 康宏

    健康ビジネスサミット うおぬま会議2017in新潟市 新潟県 新潟市  2017.10 

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  • Beneficial effects of rice endosperm protein on chronic kidney disease-mineral and bone disorder(CKD-MBD) in Zucker diabetic fatty rats. International conference

    Watanabe R, Kubota M, Sugaki S, Hosojima M, Saito A, Fujii M, Sasagawa I, Fujimura S, Kadowaki M

    IUNS 21st International Congress of Nutrition  2017.10 

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  • 新規糖尿病治療薬による腎保護効果 Invited

    細島康宏, 蒲澤秀門, 鈴木芳樹, 成田一衛, 斎藤亮彦

    第47回日本腎臓学会東部学術大会  2017.10 

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  • ボルテゾミブが奏功した意識不明の単クローン性ガンマグロブリン血症(MGUS)に伴う重鎖沈着症(HCDD)の一例

    須藤真則, 若松拓也, 石川友美, 羽深将人, 細島康宏, 山本卓, 伊藤由美, 今井直史, 金子佳賢, 瀧澤淳, 成田一衛

    第47回日本腎臓学会東部学術大会  2017.10 

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  • Plant versus Animal Protein Improves Anti-Inflammatory Effects of HDL and Lessens CKD-Induced Atherosclerosis International conference

    Kaseda R, Hosojima M, Kuwahara S, Kabasawa H, Aoki H, Higuchi Y, Kon V, Maruyama K, Narita I, Saito A

    American Society of Nephrology 50th Annual Meeting  2017.10 

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  • 糖尿病性腎症について

    細島 康宏

    慢性腎臓病(CKD)予防講座 糖尿病性腎症予防のための健康講演会  2017.9 

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  • ゾレドロン酸による高度代謝性アシドーシスおよび急性腎障害に対して持続血液濾過透析が奏功した一例

    大滝耕平, 若松拓也, 細島康宏, 保坂聖子, 山本卓, 金子佳賢, 後藤眞, 成田一衛

    第44回東北腎不全研究会  2017.9 

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  • 医学から見た和食と健康

    細島 康宏

    フードフォーカスinにいがた2016 第9回市民公開講座 新潟「食と健康フォーラム」  2016.11 

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    Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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  • 腎臓病と栄養・食事

    細島 康宏

    平成28年度新潟大学ラジオ公開講座 BSNラジオ  2016.2 

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    Language：Japanese   Presentation type：Media coverage  

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  • 慢性腎臓病患者さんにおける食事療法～たんぱく質を中心に～

    細島 康宏

    第7回天地腎 (市民公開メディカルセミナーin新発田)  2015.8 

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Industrial property rights

  • ノロウイルスの感染リスクの有無を決定する方法

    齋藤 亮彦, 細島 康宏, 蒲澤 秀門, 青木 信将, 永野 啓, 関根 盛, 宗片 圭祐

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    Applicant：国立大学法人 新潟大学

    Application no：JP2021037090  Date applied：2021.10

    Patent/Registration no：特許第7580730号  Date registered：2024.11 

    J-GLOBAL

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  • 幼少期投与用の肥満及び/又は肥満関連腎症予防組成物、幼少期投与用の肥満及び/又は肥満関連腎症予防薬、食品、並びに肥満及び/又は肥満関連腎症を予防する方法

    齋藤 亮彦, 細島 康宏, 樋口 裕樹

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    Applicant：国立大学法人 新潟大学

    Application no：特願2017-061684  Date applied：2017.3

    Announcement no：特開2018-162238  Date announced：2018.10

    Patent/Registration no：特許第6970955号  Date registered：2021.11 

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  • 幼少期投与用の肥満及び/又は肥満関連腎症予防組成物、幼少期投与用の肥満及び/又は肥満関連腎症予防薬、食品、並びに肥満及び/又は肥満関連腎症を予防する方法

    齋藤 亮彦, 細島 康宏, 樋口 裕樹

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    Applicant：国立大学法人 新潟大学

    Application no：特願2017-061684  Date applied：2017.3

    Announcement no：特開2018-162238  Date announced：2018.10

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  • メガリン拮抗剤

    齋藤 亮彦, 青木 信将, 堀 好寿, 桑原 頌治, 細島 康宏, 岩田 博司, 松田 砂織

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    Applicant：EAファーマ株式会社

    Application no：特願2015-559110  Date applied：2015.1

    Patent/Registration no：特許第6508655号  Date registered：2019.4 

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  • メガリン拮抗剤

    齋藤 亮彦, 青木 信将, 堀 好寿, 桑原 頌治, 細島 康宏, 岩田 博司, 松田 砂織

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    Applicant：EAファーマ株式会社

    Application no：JP2015051718  Date applied：2015.1

    Publication no：WO2015-111666  Date published：2015.7

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  • 米タンパク質を有効成分とする血清尿酸低下剤

    斎藤 亮彦, 細島 康宏, 門脇 基二, 久保田 真敏, 藤井 幹夫, 近藤 葉月

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    Applicant：亀田製菓株式会社

    Application no：特願2015-554716  Date applied：2014.12

    Patent/Registration no：特許第6088071号  Date registered：2017.2  Date issued：2017.2

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  • 米タンパク質を有効成分とする血清尿酸低下剤

    斎藤 亮彦, 細島 康宏, 門脇 基二, 久保田 真敏, 藤井 幹夫, 近藤 葉月

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    Applicant：亀田製菓株式会社

    Application no：JP2014082385  Date applied：2014.12

    Publication no：WO2015-098474  Date published：2015.7

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  • 米タンパク質を有効成分とする血清尿酸低下剤

    斎藤 亮彦, 細島 康宏, 門脇 基二, 久保田 真敏, 藤井 幹夫, 近藤 葉月

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    Applicant：亀田製菓株式会社, 国立大学法人 新潟大学

    Application no：特願2013-265887  Date applied：2013.12

    Announcement no：特開2016-172693  Date announced：2016.9

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  • 米糠タンパク質を含む糖尿病性腎症進展抑制用栄養組成物

    門脇 基二, 久保田 真敏, 斎藤 亮彦, 細島 康宏, 渡邊 令子, 橋本 博之

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    Applicant：国立大学法人 新潟大学, 公立大学法人新潟県立大学, 築野食品工業株式会社

    Application no：特願2013-118021  Date applied：2013.6

    Announcement no：特開2014-233266  Date announced：2014.12

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  • タンパク質栄養組成物

    門脇 基二, 斎藤 亮彦, 細島 康宏, 久保田真敏, 渡邊 令子, 藤井 幹夫

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    Applicant：国立大学法人 新潟大学, 公立大学法人新潟県立大学, 亀田製菓株式会社

    Application no：特願2013-017197  Date applied：2013.1

    Announcement no：特開2014-147315  Date announced：2014.8

    Patent/Registration no：特許第6139150号  Date registered：2017.5  Date issued：2017.5

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  • タンパク質栄養組成物

    門脇 基二, 斎藤 亮彦, 細島 康宏, 久保田真敏, 渡邊 令子, 藤井 幹夫

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    Applicant：国立大学法人 新潟大学, 公立大学法人新潟県立大学, 亀田製菓株式会社

    Application no：特願2013-017197  Date applied：2013.1

    Announcement no：特開2014-147315  Date announced：2014.8

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Awards

  • 学会賞（アルビレオ賞）

    2022.12   日本病態栄養学会  

    細島康宏

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  • 新潟県医師会学術奨励賞

    2020.3   新潟県医師会  

    細島康宏

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  • 医学生・研修医の日本内科学会ことはじめ2019 優秀指導教官賞

    2019.5   日本内科学会  

    細島 康宏

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  • 有壬記念学術奨励賞

    2017   新潟大学医学部学士会  

    細島康宏

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  • 平成27年度学術研究助成金

    2015   新潟県医師会  

    細島康宏

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  • 最優秀奨励賞

    2014   第6回腎疾患と高血圧研究会  

    細島康宏

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  • 優秀演題賞

    2012   Advance研究会  

    細島康宏

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Research Projects

  • 抗刷子縁抗体病の実態調査と病態解明に関する研究

    Grant number：23K07667

    2023.4 - 2026.3

    System name：科学研究費助成事業

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    蒲澤 秀門, 細島 康宏, 斎藤 亮彦

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    Grant amount：\4810000 （ Direct Cost: \3700000 、 Indirect Cost：\1110000 ）

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  • 前向きコホート10年追跡による尿細管マーカーのCKD発症・進展予測能の検討

    Grant number：23K07694

    2023.4 - 2026.3

    System name：科学研究費助成事業

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    蒲澤 佳子, 伊藤 由美, 細島 康宏, 斎藤 亮彦

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

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  • メガリンの構造と機能の精密解析に基づく腎臓病の病態解明と診断・治療の新たな創薬

    Grant number：21H02934

    2021.4 - 2025.3

    System name：科学研究費助成事業

    Research category：基盤研究(B)

    Awarding organization：日本学術振興会

    斎藤 亮彦, 後藤 佐和子, 細島 康宏

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    Grant amount：\17160000 （ Direct Cost: \13200000 、 Indirect Cost：\3960000 ）

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  • メガリンの構造と機能の精密解析に基づく腎臓病の病態解明と診断・治療の新たな創薬

    Grant number：23K21436

    2021.4 - 2025.3

    System name：科学研究費助成事業

    Research category：基盤研究(B)

    Awarding organization：日本学術振興会

    斎藤 亮彦, 細島 康宏, 後藤 佐和子

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    Grant amount：\17160000 （ Direct Cost: \13200000 、 Indirect Cost：\3960000 ）

    メガリンは近位尿細管上皮細胞に発現するエンドサイトーシス受容体で、糸球体を濾過する生理的リガンドの他、腎毒性のタンパク質や薬剤等の「入り口」分子として様々な腎臓病の発症・進展に関わる。本研究の目的は,我々が進めてきたメガリンの構造・機能解析を深化させ、腎臓病の病態解明と診断・治療における「メガリン創薬」を推進することである。具体的には、(A)メガリンの精密な立体構造解析やリガンド結合の物理化学的相互作用解析によって腎毒性リガンドとメガリンの結合様式を解明し、「メガリン拮抗薬」の開発を進める。(B)質量分析法等によるメガリンの構造解析を通して糖尿病性腎臓病の病態を解析し、「メガリン機能抑制薬」による治療理念を提唱する。(C)メガリンの細胞外ドメインの切断・尿中逸脱機序を明らかにすることで「尿中メガリン検査薬」の意義付けを深める。まず、(A) ラット腎から近位尿細管刷子縁膜を抽出・可溶化後、抗メガリンモノクローナル抗体によるアフィニティークロマトグラフィーおよびゲル濾過クロマトグラフィーによりメガリンを精製し、クライオ電子顕微鏡を用いて立体構造を明らかにした。その構造の詳細な解析により、メガリンが多様なリガンドと結合するメカニズムを解明した。また、インシリコ解析により、メガリン拮抗薬であるシラスタチンがメガリンを阻害するメカニズムを解析した。また、表面プラズモン共鳴法を利用して、新規メガリン拮抗薬をスクリーニングするための評価系の構築を行った。(B) マウス・ラット腎近位尿細管の細胞膜（微絨毛）および細胞内におけるメガリンの構造の違いによる分布性を、生化学的および免疫組織化学的に検証した。さらに、質量分析法等によるメガリンの構造解析の基礎検討を行った。また、(C) 2型糖尿病モデルdb/dbマウスにおいて、尿中細胞外ドメイン切断型メガリンの排泄機序の検討を行った。

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  • 糖尿病性腎臓病の新規尿中マーカー、細胞外ドメイン切断型メガリンの尿中逸脱機序

    Grant number：20K08629

    2020.4 - 2023.3

    System name：科学研究費助成事業 基盤研究(C)

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    細島 康宏

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

    糖尿病性腎臓病の早期診断と予後予測においては尿中アルブミンの測定が重要であるが、様々な問題点も指摘されており、新しいバイオマーカーの開発が求められている。これまでに我々は、腎臓の近位尿細管エンドサイトーシス受容体であるメガリンに着目し、その発現調節機構、他分子との相互作用に関する基礎研究を行うとともに、ヒト尿中メガリン(全長型および細胞外ドメイン切断型)ELISA測定系を開発した。その結果、それらのメガリンの尿中排泄量測定が、糖尿病性腎臓病の重症度や病態の評価に有用であり、既存のバイオマーカーとは異なる新しいマーカーになり得る可能性を示してきた。さらに、細胞外ドメイン型尿中メガリンが新規の糖尿病関連薬などにより鋭敏に増減することも明らかにしてきたが、その尿中への逸脱機序の詳細は未だ十分に解明されていない。そこで本研究は、細胞外ドメイン型メガリンの尿中逸脱機序の詳細を明らかにすることを目的としている。
    研究は主に、「細胞内輸送実験系を用いたメガリンの細胞内リサイクリングと細胞外逸脱の関係」、「DKDの進展時における細胞外ドメイン型尿中メガリンの逸脱機序の解析」、「SGLT2阻害薬使用時の細胞外ドメイン型尿中メガリンの逸脱機序」、「バルドキソロンメチル使用時の細胞外ドメイン型尿中メガリンの逸脱機序」の4つの内容を明らかにしていく計画であった。今年度は、培養細胞においてメガリンの細胞内リサイクリングと細胞外逸脱の関係を検討し得る実験系を確立しただけでなく、糖尿病性腎臓病モデルマウスを用いた検討、さらにはSGLT2阻害薬およびバルドキソロンメチルを使用した動物実験を行い、その予備的なデータを得ることができた。来年度以降も継続的に検討を行っていく予定である。

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  • 23Na-MRIを用いたネフローゼ症候群の病態生理の解析

    Grant number：20K08586

    2020.4 - 2023.3

    System name：科学研究費助成事業

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    忰田 亮平, 成田 一衛, 細島 康宏, 斎藤 亮彦, 寺田 康彦

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

    腎臓内でのNa+ハンドリングの可視化は、腎臓領域の研究での悲願であり、特に、ネフローゼ症候群では、Na+の貯留と浮腫の成因として、underfillingとoverfillingの機序が提唱されているが、腎臓内のNa+の全体像を明らかにできる方法は今までなかった。申請者らは、マウスのごく小さな腎臓に対して、23Na-MRI（磁気共鳴映像法）を用いて23Naをもとにした画像化に成功し、水の効率的な再吸収が可能となる対向流増幅系のNa+の濃度勾配・Na+の貯留の状態を可視化した。この23Na-MRI画像をもとに、今まで理解できなかったネフローゼ症候群における「腎臓全体のNa+のハンドリング・Na+の貯留」と「Na+の再吸収に関わるチャネル・トランスポーター」の関係を明らかにすることで、病態生理の解明を試みる。腎臓全体でのネフローゼ症候群のNa+の再吸収に関わる機構の異常を解明することを目的とする。①ネフローゼモデルマウス（NEP25マウス）を用いて、ネフローゼ症候群といった病的状態では、腎臓内のNa+再吸収に関わる作用点 (チャネル・トランスポーター)がどのように変化するか明らかにする。②さらに、Na+の再吸収に影響する薬剤、具体的には、副腎皮質ステロイド、SGLT2阻害薬、RAS阻害薬、トルバプタン、ミネラルコルチコイド受容体(MR)拮抗薬、ヒト心房性ナトリウム利尿ペプチド(hANP)、バソプレッシン等について検討する。③腎臓内Agt、AngII量や挙動と画像所見を元にしたNa+の再吸収機構の関連について検討する。

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  • Development of megalin-targeted strategies for diagnosis, prevention, and treatment of chronic kidney disease and acute kidney injury

    Grant number：18H02825

    2018.4 - 2021.3

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    Saito Akihiko

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    Grant amount：\17160000 （ Direct Cost: \13200000 、 Indirect Cost：\3960000 ）

    The proximal tubular endocytosis receptor, megalin, is involved in the reabsorption and metabolism of various proteins, peptides, and drugs that are filtrated through the glomerulus. In this study, we have investigated (1) the mechanism of urinary megalin excretion and its diagnostic significance, (2) issues for the establishment of megalin suppression therapy to prevent the development and progression of chronic kidney disease: (2)-① the involvement of megalin in the renal renin-angiotensin system (RAS), (2)-② the effect of megalin suppression at different sites in the proximal tubule, (3) issues for the establishment of megalin antagonist therapy for the prevention of acute kidney injury: (3)-① the significance of megalin antagonist therapy for prevention of contrast-induced nephropathy, and (3)-② screening systems for novel megalin antagonists.

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  • Significance of urinary megalin excretion linked to the pathophysiology of obesity- or metabolic syndrome-related nephropathy

    Grant number：17K09690

    2017.4 - 2020.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    Hosojima Michihiro

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

    Megalin, which is expressed in proximal tubular cells of the kidney, constitutes a renal “gateway” for nephrotoxic substances, being involved in the development of obesity- or metabolic syndrome-related nephropathy and diabetic nephropathy. In this study, we have established novel ELSIA systems to measure urinary A- (extracellular domain type) and C-megalin (full-length type) in mice. In the future, these technologies will contribute greatly to the basic research on megalin. In addition, our study in patients with type 2 diabetes has shown that urinary A- and C-megalin are novel biomarkers different from existing ones. Measuring both forms of urinary megalin in patients with diabetic nephropathy would enable us to predict future progression of the disease.

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  • メガリンを標的とした腎機能温存・再生療法の開発

    2016.4 - 2019.3

    System name：腎疾患実用化研究事業

    Awarding organization：国立研究開発法人日本医療研究開発機構

    斎藤 亮彦

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    Grant type：Competitive

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  • Investigation of the mechanism underlying urinary excretion of megalin, a novel biomarker of diabetic kidney disease

    Grant number：26860630

    2014.4 - 2017.3

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists (B)

    Research category：Grant-in-Aid for Young Scientists (B)

    Awarding organization：Japan Society for the Promotion of Science

    Hosojima Michihiro, DE Shankhajit, KUWAHARA Shoji, KABASAWA Hideyuki, SAITO Akihiko

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    Grant amount：\3770000 （ Direct Cost: \2900000 、 Indirect Cost：\870000 ）

    I studied the mechanism underlying urinary excretion of megalin, a multiligand endocytic receptor in the proximal tubules, in diabetic kidney disease (DKD). Urinary extracellular vesicle (UEV) excretion and full-length megalin (C-megalin) content in UEVs or in their exosomal fraction increased along with the progression of the albuminuric stages in patients with type 2 diabetes mellitus (T2DM). C-megalin excretion from cultured immortalized rat proximal tubule cells via extracellular vesicles was increased via lysosomal dysfunction in association with megalin-mediated cellular uptake of advanced glycation endproducts, which is significantly blocked by an exosome-specific inhibitor, GW4869. In a high-fat diet-induced, megalin-mediated DKD model in mice, urinary C-megalin excretion also increased via UEVs. Collectively, exocytosis-mediated urinary C-megalin excretion is linked with the megalin-mediated mechanism underlying the development and progression of DKD in T2DM.

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