ITOH Hiroshi

写真a

Affiliation

School of Medicine, Center for Preventive Medicine (Shinanomachi)

Position

Project Professor (Non-tenured) （Keio University）

External Links
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Profile 【 Display / hide 】

  • 2024-present Director, Research Support Center, Shizuoka General Hospital
    2023-present Specially Appointed Professor (full time) Center for Preventive Medicine, Keio University,
    Professor Emeritus of Keio University
    2023-present President, Japan Optimized Nutri-Dense Meals Association
    2021-present Vice President, Shizuoka Graduate University Public Health
    2021-present Visiting Professor, Nagoya City University
    2019-2023 Director, Center for Diabetes Preemptive Medicine, Keio University Hospital
    2015-2017 Senior Investigator, Japan Society for the Promotion of Science
    2015-2024 Vice Director, Center for Supper Centenarian Medical Research, Keio University
    2010-2019 Vice Director, Center for Integrated Medical Research, Keio University
    2006-2023 Professor and Chairman Department of Endocrinology, Metabolism and Nephrology Keio University School of Medicine
    2002-2006 Associate Professor and Vice Chairman 　 Department of Medicine and Clinical Science Kyoto niversity Graduate School of Medicine
    2001-2002 Associate Professor Department of Medicine and Clinical Science Kyoto University Graduate School of Medicine
    1993-2000 Assistant Professor Department of Medicine and Clinical Science Kyoto University Graduate School of Medicine 　　　　　　　　　 　　　　　　　　　
    1990-1991 Postdoctoral Fellow, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA (mentor: Prof. Victor J. Dzau)
    1989-1990 Postdoctoral Fellow, Division of Vascular Medicine and Atherosclerosis, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
    1989 Ph.D., Kyoto University School of Medicine
    1983 M.D., Kyoto University School of Medicine

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Other Affiliation 【 Display / hide 】

  • School of Medicine, 内科学（腎臓・内分泌・代謝）, Department of Endocrinology,Metabolism and Nephrology

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Academic Background 【 Display / hide 】

  • 1983.03

    Kyoto University, 医学部, 医学科

    University, Graduated

  • 1989.03

    Kyoto University, 医学研究科

    Graduate School, Completed, Doctoral course

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Licenses and Qualifications 【 Display / hide 】

  • 第1種放射線取扱主任者, 1980

  • ECFMG免許, 1983

  • 医師免許, 1983

  • 日本内分泌学会内分泌代謝科専門医, 1995

  • 日本糖尿病専門医, 2003

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Research Areas 【 Display / hide 】

  • Life Science / Nephrology

  • Life Science / Metabolism and endocrinology

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Research Keywords 【 Display / hide 】

  • metabolism

  • endocrinology

  • diabtes mellitus

  • hypertension

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Papers 【 Display / hide 】

  • DNA damage in proximal tubules triggers systemic metabolic dysfunction through epigenetically altered macrophages

    Nishimura E.S., Hishikawa A., Nakamichi R., Akashio R., Chikuma S., Hashiguchi A., Yoshimoto N., Hama E.Y., Maruki T., Itoh W., Yamaguchi S., Yoshino J., Itoh H., Hayashi K.

    Nature Communications 16 ( 1 ) 3958 2025.12

    　View Summary

    DNA damage repair is a critical physiological process closely linked to aging. The accumulation of DNA damage in renal proximal tubular epithelial cells (PTEC) is related to a decline in kidney function. Here, we report that DNA double-strand breaks in PTECs lead to systemic metabolic dysfunction, including weight loss, reduced fat mass, impaired glucose tolerance with mitochondrial dysfunction, and increased inflammation in adipose tissues and the liver. Single-cell RNA sequencing analysis reveals expansion of CD11c+ Ccr2+ macrophages in the kidney cortex, liver, and adipose tissues and Ly6Chi monocytes in peripheral blood. DNA damage in PTECs is associated with hypomethylation of macrophage activation genes, including Gasdermin D, in peripheral blood cells, which is linked to reduced DNA methylation at KLF9-binding motifs. Macrophage depletion ameliorates metabolic abnormalities. These findings highlight the impact of kidney DNA damage on systemic metabolic homeostasis, revealing a kidney-blood-metabolism axis mediated by epigenetic changes in macrophages.

  • Effect of administration and withdrawal of the sodium-glucose cotransporter 2 inhibitor, tofogliflozin, on renal protection in individuals with type 2 diabetes mellitus and diabetic nephropathy: A multicenter, single-arm study (RESTORE-nephropathy study)

    Shigeta A., Tanaka M., Meguro S., Morimoto J., Imai T., Yamauchi A., Kanazawa Y., Kawai T., Azuma K., Yamada S., Endo S., Itoh H., Hayashi K.

    Journal of Diabetes Investigation 16 ( 5 ) 817 - 826 2025.05

    ISSN  20401116

    　View Summary

    Aims/Introduction: The mechanisms of the renoprotective effects of sodium-glucose cotransporter 2 inhibitors are unknown. This study aimed to explore the effect and mechanism of tofogliflozin on urinary albumin by administration, withdrawal, and re-administration. Materials and Methods: Individuals with type 2 diabetes mellitus and stage 2 or 3 diabetic nephropathy were enrolled. Tofogliflozin was administered for 24 weeks, withdrawn for 12 weeks (withdrawal period), and re-administered for 24 weeks. The primary endpoint was the change in urinary albumin/creatinine ratio (UACR). The secondary endpoints included hemoglobin A1c (HbA1c), hepatic biomarkers, lipid profiles, physical examinations, and blood counts. Results: A total of 47 individuals were enrolled. UACR significantly decreased throughout the observation period. It also significantly decreased, increased, and again decreased during the period of the 1st administration, withdrawal, and re-administration, respectively. HbA1c, body weight, waist circumference, and systolic blood pressure also showed the same tendency. Aspartate aminotransferase and alanine aminotransferase significantly decreased throughout the observation period, but did not increase during the withdrawal period. Conclusions: Urinary albumin improved during the administration of tofogliflozin and worsened during its withdrawal, suggesting the reversibility of its renoprotective effect. The administration of tofogliflozin should be continued to avoid the reversal of glycemic control, renoprotective effects, and other beneficial effects.

  • A Randomized Clinical Trial of ICT-based Interventions for Sodium and Potassium Regulation in Healthy Adults.

    Yuichiro Yano, Kaori Kitaoka, Takayoshi Ohkubo, Tomonori Okamura, Hiroshi Kanegae, Katsushi Yoshita, Rumi Tsukinoki, Yukiko Okami, Koichi Node, Hiromi Rakugi, Hiroshi Itoh, Katsuyuki Miura

    American journal of hypertension  2025.04

    ISSN  0895-7061

    　View Summary

    BACKGROUND: There is limited knowledge regarding effective strategies, including information and communication technology (ICT)-based interventions, to reduce sodium intake and increase potassium intake in healthy individuals. METHODS: We conducted a three-month randomized controlled trial involving healthy adult employees with spot urine sodium-to-potassium ratios (spot UNa/UK) ≥4.0 or estimated 24-hour salt intake ≥10g. Estimated 24-hour UNa and UK were calculated using the Tanaka formula. Participants were assigned to one of four groups: (1) online education, where participants monitored their spot UNa/UK and received feedback from dieticians (n=84); (2) messaging, with similar self-monitoring and dietician messages (n=84); (3) self-learning, provided with an educational leaflet (n=87); and (4) a control group (n=87). The primary outcome was the change in spot UNa/UK ratios, and secondary outcomes included changes in estimated 24-hour UNa and UK. The trial protocol specified a hierarchical order for testing the interventions, anticipating the highest efficacy in the online education group. RESULTS: After the intervention, the online education group showed a decrease in spot UNa/UK ratios (mean -0.9 [95% CI -1.8 to 0.0], p=0.052) compared to the control group. The increase in estimated 24-hour UK excretion was larger in the online education compared to control group (mean +2.5 mmol/day [95% CI -0.3 to 5.3], p=0.085). The difference in estimated 24-hour UNa excretion between the online education and control groups was -4.3 mmol/day (95% CI -15.5 to 6.9, p=0.45). CONCLUSIONS: Combining self-monitoring of sodium and potassium intake with ICT-based interventions, including online nutritional education, was associated with a modest reduction in the estimated ratios of sodium and potassium intake in healthy individuals.

  • Efficacy of Esaxerenone Plus a Renin-Angiotensin System Inhibitor or Calcium Channel Blocker for Nocturnal Hypertension: A Post Hoc Analysis.

    Kario K, Ito S, Itoh H, Rakugi H, Okuda Y, Yamakawa S

    American journal of hypertension  2025.04

    ISSN  0895-7061

  • Effective calcineurin inhibitor treatment in adult-onset steroid-resistant nephrotic syndrome with a novel splice donor site variant of TRPC6: a case report

    Nagasaka T., Uchiyama K., Hama E.Y., Kojima D., Kaneko K., Yoshimoto N., Yasuda I., Yamada M., Miya F., Suzuki H., Tajima T., Yamaguchi S., Hayashi K., Kanda T., Hashiguchi A., Kosaki K., Itoh H.

    CEN Case Reports 14 ( 2 ) 208 - 216 2025.04

    　View Summary

    Transient receptor potential canonical 6 (TRPC6) variants, which were initially detected in adult-onset familial focal segmental glomerulosclerosis (FSGS), were also identified in pediatric-onset one. Here, we present a patient with adult-onset steroid-resistant nephrotic syndrome (SRNS) who harbored a likely pathogenic TRPC6 variant and partially responded to calcineurin inhibitors (CNIs). A 44-year-old woman with stable rheumatoid arthritis, systemic lupus erythematosus, and Sjögren’s syndrome was presented with nephrotic syndrome. Her renal biopsy results showed minor glomerular abnormalities. Upon admission, she was treated with steroids for around 4 weeks, but it was ineffective. After 1–2 weeks of cyclosporine A (CyA) administration, urine output increased, renal function improved without a decrease in proteinuria, and she was discharged. Her renal function was maintained for 2 months, but after a CyA dose reduction, she was again admitted to the hospital due to relapsing edema, decreased urine output, and worsening renal function. CyA was replaced by tacrolimus (TAC). A second renal biopsy showed nearly the same findings as the first except for tubulointerstitial lesions. After 1–2 weeks of TAC administration, urine output increased, and renal function improved. However, urinary protein levels did not decrease as before. After discharge, a whole exome analysis revealed a heterozygous splice donor site variant NM_004621.6;c.2644 + 1G > A in TRPC6. Genetic testing identified a novel splice donor site variant of TRPC6 in a patient with adult-onset SRNS, which prevented unnecessary steroid continuation. The safety and efficacy of CNI in TRPC6 glomerulopathy must be evaluated in future larger studies with longer follow-up.

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Reviews, Commentaries, etc. 【 Display / hide 】

  • Correction to: Predicting exacerbation of renal function by DNA methylation clock and DNA damage of urinary shedding cells: a pilot study (Scientific Reports, (2024), 14, 1, (11530), 10.1038/s41598-024-62405-4)

    Hishikawa A., Nishimura E.S., Yoshimoto N., Nakamichi R., Hama E.Y., Ito W., Maruki T., Nagashima K., Shimizu‑Hirota R., Takaishi H., Itoh H., Hayashi K.

    Scientific Reports 14 ( 1 ) 32157 2024.12

    　View Summary

    Correction to: Scientific Reportshttps://doi.org/10.1038/s41598-024-62405-4, published online 21 May 2024 The Acknowledgements section in the original version of this Article was incomplete. “We acknowledge Dr. Hideaki Nakaya for assistance during the initial stage of this study. This study was supported by the Grants for Scientific Research (22H03091) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan and a grant from the Japan Foundation for Applied Enzymology.” now reads: "We acknowledge Dr. Hideaki Nakaya for assistance during the initial stage of this study. This study was supported by the Grants for Scientific Research (22H03091) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan, the JST FOREST Program (Grant number JPMJFR210V, Japan) and a grant from the Japan Foundation for Applied Enzymology.” The original Article has been corrected.

  • FPIES負荷試験陰性後の自宅摂取での症状誘発

    夏目 統, 幸田 昌樹, 伊藤 裕, 早野 聡, 坂井 聡, 櫻井 史紀, 犬塚 祐介, 加藤 由希子, 安岡 竜平, 田口 智英

    日本小児アレルギー学会誌 ((一社)日本小児アレルギー学会)  38 ( 4 ) 398 - 398 2024.09

    ISSN  0914-2649

  • CKD予後予測因子としてのDNAメチル化年齢の可能性

    菱川 彰人, 杉田 絵里那, 吉本 憲史, 中道 蘭, 吉田 英莉子, 清水 良子, 高石 官均, 伊藤 裕, 林 香

    日本腎臓学会誌 ((一社)日本腎臓学会)  66 ( 4 ) 580 - 580 2024.06

    ISSN  0385-2385

  • DNA修復因子ERCC1はポドサイトの恒常性維持に必須である

    吉田 英莉子, 中道 蘭, 菱川 彰人, 吉本 憲史, 西村 絵里那, 丸木 友美, 伊藤 亘, 伊藤 裕, 林 香

    日本腎臓学会誌 ((一社)日本腎臓学会)  66 ( 4 ) 609 - 609 2024.06

    ISSN  0385-2385

  • GLP-1シグナリングによる獲得免疫調節を介した1型糖尿病の治療法の開発

    伊藤 新, 遊木 一成, 入江 潤一郎, 伊藤 裕, 林 香

    糖尿病 ((一社)日本糖尿病学会)  67 ( Suppl.1 ) S - 153 2024.04

    ISSN  0021-437X

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Presentations 【 Display / hide 】

  • Obesity-associated gut inflammation and gut microbiota

    Itoh Hiroshi

    International Congress on Obesity and Metabolic Syndrome (Seoul, Korea) , 

    2017.09
    , 

    Symposium, workshop panel (nominated)

  • Does intensive treat-to-target LDL-C lowering therapy using statin in patients of diabetic retinopathy reduce cardiovascular events?:the EMPATHY study

    Itoh Hiroshi

    European Society of Cardiology Congress 2017, 

    2017.08
    , 

    Oral presentation (general)

  • 4. Diabetic hypertensives in Asia; Are we different from Westerners?

    Itoh Hiroshi

    APSH/ISH Summer School,2017 (Shanghai, China) , 

    2017.08
    , 

    Public lecture, seminar, tutorial, course, or other speech

  • "Organ memory" and Pre-emptive medicine for hypertension

    Itoh Hiroshi

    APSH/ISH Summer School,2017 (Shanghai, China) , 

    2017.08
    , 

    Public lecture, seminar, tutorial, course, or other speech

  • “メタボエイジング”と“イムノエイジング”を結ぶもの

    Itoh Hiroshi

    第17回日本抗加齢医学会総会, 

    2017.06
    , 

    Public lecture, seminar, tutorial, course, or other speech

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • 母児概日リズム同期と次世代疾患感受性の多層多元的代謝リズムパネルからの理解

    2021.07
    -
    2026.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Challenging Research (Pioneering), Principal investigator

  • Spiral progression of DNA damage repair, epigenetic alterations and metabolic changes in metabolic kidney diseases

    2020.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (A) , Principal investigator

  • 代謝産物を介した多細胞間ネットワークの統合的解析による臓器機能in toto把握

    2017.06
    -
    2020.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Challenging Research (Pioneering), Principal investigator

  • The significant role of the kidney as a central organ for metabolic organ interrelationship

    2017.04
    -
    2020.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (A) , Principal investigator

  • Visualization of small metabolites in the kidney for elucidation of pathophysiology of ischemic nephropathy

    2016.04
    -
    2017.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Challenging Exploratory Research, Principal investigator

    　View Summary

    The kidney plays an essential role in the maintenance of physiological homeostasis of fluid and electrolytes in the body. Adenosine is a well known regulator of renal function and blood flow; however, the normal distribution of adenosine in the kidney has not been well elucidated. Matrix-assisted laser desorption/ionization (MALDI) - imaging mass spectrometry (IMS) is a novel technology for visualizing the distributions of molecules in situ. Small metabolites in the kidney has not been examined by the method thus far. In the present study, we identified a remarkable accumulation of adenosine in outer stripes of outer medulla (OSOM). The local accumulation of adenosine in OSOM may play a significant role for the physiological functions of adenosine such as the regulation of interstitial blood flow in the kidney.

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Awards 【 Display / hide 】

  • 平成29年度井村臨床研究賞

    2017.08

  • 平成28年度日本糖尿病合併症学会Expert Investigator Award

    2016.10

  • 第18回日本心血管内分泌代謝学会　高峰譲吉賞

    2014.12

  • 第3回抗加齢研究奨励賞（臨床の部）

    2011

  • 上原記念生命科学財団 研究助成金

    2012

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Courses Taught 【 Display / hide 】

  • CLINICAL CLERKSHIP IN NEPHROLOGY, ENDOCRINOLOGY, AND METABOLISM

    2025

  • CLINICAL CLERKSHIP IN INTERNAL MEDICINE (NEPHROLOGY, ENDOCRINOLOGY, AND METABOLISM)

    2025

  • LECTURE SERIES, INTERNAL MEDICINE (NEPHROLOGY, ENDOCRINOLOGY, AND METABOLISM)

    2024

  • CLINICAL CLERKSHIP IN NEPHROLOGY, ENDOCRINOLOGY, AND METABOLISM

    2024

  • CLINICAL CLERKSHIP IN INTERNAL MEDICINE (NEPHROLOGY, ENDOCRINOLOGY, AND METABOLISM)

    2024

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Memberships in Academic Societies 【 Display / hide 】

  • 日本内分泌学会

    　

  • 日本高血圧学会, 

    1985.10
    -
    Present

  • 日本内科学会

    　

  • 日本肥満学会, 

    2006.09
    -
    Present

  • 日本心血管内分泌代謝学会

    　

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