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 】

  • 医師免許, 1983

  • 日本内科学会認定内科医, 1993.09

  • 日本内分泌学会内分泌代謝科専門医, 1995

  • 日本内分泌学会指導医, 2004

  • 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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Books 【 Display / hide 】

  • Mitochondria and Antiaging Medicine: NAD+ Metabolic Intermediates and Antiaging

    Yoshino J., Itoh H., Anti Aging Medicine Basics and Clinical Practice, 2025.01

    　View Summary

    Nicotinamide adenine dinucleotide (NAD+) was discovered in 1906 by British biochemist Dr. Arthur Harden and has long been known as a coenzyme that plays an important role in redox reactions. In 2000, the NAD + -dependent deacetylase activity of the aging and lifespan control factor sirtuin was discovered by Imai and Guarente at the Massachusetts Institute of Technology, leading to a dramatic development in NAD+ biology research. As a result, it is suggested that a decrease in NAD+ levels contributes to the molecular mechanisms of aging through a decrease in sirtuin activity, and also plays a part in the pathogenesis of various aging-related diseases such as diabetes, chronic kidney disease, heart failure, and Alzheimer’s disease. Currently, with about 115 years of history, NAD+ biology research is entering a second golden (renaissance) period centered on two NAD+ metabolic intermediates, nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR), and it is no exaggeration to say that it is forming the mainstream of aging and lifespan research and antiaging medicine [1, 2].

  • Mitochondria and Antiaging Medicine: Mitochondria and Antiaging

    Yoshino J., Itoh H., Anti Aging Medicine Basics and Clinical Practice, 2025.01

    　View Summary

    Mitochondria have long been known as intracellular organelles that play a central role in energy metabolism by producing adenosine triphosphate (ATP) through oxidative phosphorylation (OXPHOS), the TCA cycle, and beta-oxidation of fatty acids. Furthermore, mitochondria are thought to be involved in various biological aspects related to aging, such as the production of reactive oxygen species (ROS), genome stability, mitochondrial DNA (mtDNA) replication, mitophagy, telomere function, and cellular aging. These mitochondrial functions decline with aging and have been reported by various researchers to underlie the pathogenic mechanisms of age-related diseases such as diabetes, chronic kidney disease, heart failure, and Alzheimer’s disease [1]. It has also been suggested that mitochondria mediate the benefits of calorie restriction, which delays the onset of age-related diseases and extends the lifespan of the individual, thus increasing the importance of mitochondrial research in anti-aging medicine.

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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.

  • Patient education status regarding peritoneal dialysis: a questionnaire-based survey study

    Ryuzaki M., Inoue S., Morimoto K., Wakabayashi K., Yoshifuji A., Komatsu M., Fujii K., Kato A., Honjoh H., Wakino S., Uchiyama K., Itoh H.

    Renal Replacement Therapy 11 ( 1 )  2025.12

    　View Summary

    Background: The number of patients undergoing peritoneal dialysis (PD) in Japan has recently increased. However, Japanese guidelines for such patients’ education are not yet available. Therefore, we aimed to investigate the present status of patient education regarding PD in Japan. Methods: We used one questionnaire to perform two rounds of surveys (2019 and 2021) at institutes that managed ten patients or more on PD at the end of each year. We evaluated the facilities’ characteristics, catheter placement, PD guidance, educational content, education management, home-care environment, care of exit site, and bathing and retraining. Results: A total of 76 facilities (response rate: 26.8%) responded to the first survey, and 86 (response rate: 28.3%) to the second. The incidence of peritonitis in the valid responding institutes was 0.21 per patient-year in 2019 and 0.19 per patient-year in 2021, similar to the incidence of 0.20 per patient-year in 2022 reported by the Japanese Society for Dialysis Therapy Renal Data Registry. This indicates that the valid responding institutes may have been representative of the typical Japanese clinical level in terms of PD. In terms of catheter placement, exit-site positions were preoperatively marked by nurse in 41% of facilities in 2019 and in 37% in 2021. In terms of PD guidance, regarding the timing of the education’s initiation, the periods before PD catheter placement or during catheter embedding were more common than 1–6 days after placement in both years. In terms of the duration, 30-min to 1-h education sessions were most common, and the majority of facilities provided guidance for more than 7 days in both years. These results were different from the schedules recommended by the International Society for Peritoneal Dialysis (3 h per session for more than 5 days, initiated 10 days after the operation). Regarding educational content, most facilities provided education on PD procedures and bathing; however, in some facilities, the content did not include dietary guidance, the importance of residual kidney function, medications, laboratory data, troubleshooting, medical security, or social resources. In both years, approximately 70% of the instructional items comprised the PD procedure, exit-site care, bathing, and infection prevention. Regarding education management, the patients’ levels of understanding were evaluated via manual or oral tests in most of the facilities. Regarding the method of demonstration, the entire procedure was explained during the demonstration in almost all institutes. Nurses in > 50% of facilities visited the patients’ homes either when PD was introduced or as needed. The majority of facilities did not use cognitive-function tests when PD was introduced to older adults. Regarding exit-site care and bathing, no consensus existed. Almost half of facilities performed regular, scheduled retraining. Conclusions: In this study, patients’ PD-related educational situations differed from those recommended by the International Society for Peritoneal Dialysis, and no consensus for exit-site care or bathing existed. To improve the clinical level of PD practice in Japan, original Japanese guidelines for patients’ PD education are required, for which our results may serve as the foundation.

  • Triglyceride/high density lipoprotein cholesterol index and future cardiovascular events in diabetic patients without known cardiovascular disease

    Nakashima R., Ikeda S., Shinohara K., Matsumoto S., Yoshida D., Ono Y., Nakashima H., Miyamoto R., Matsushima S., Kishimoto J., Itoh H., Komuro I., Tsutsui H., Abe K.

    Scientific Reports 15 ( 1 ) 9217 2025.12

    　View Summary

    The triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) index, calculated as TG divided by HDL-C, has been suggested as a predictor of cardiovascular disease (CVD). We investigated the association between the TG/HDL-C index and CVD events in type 2 diabetes mellitus (T2DM) patients with retinopathy and hyperlipidemia but no known CVD, enrolled in the EMPATHY study, which compared intensive and standard statin therapy (targeting LDL-C levels < 70 mg/dL and ≥ 100 to < 120 mg/dL, respectively). A total of 4665 patients were divided into high (TG/HDL-C ≥ 2.5, n = 2013) and low (TG/HDL-C < 2.5, n = 2652) TG/HDL-C index groups. During a median follow-up of 36.8 months, 260 CVD events occurred. The high TG/HDL-C index group had higher CVD risk than the low group (HR 1.89, 95% CI 1.45–2.47, p < 0.001). This association remained consistent across subgroups. A trend toward interaction between TG/HDL-C index and statin treatment allocation for CVD risk was observed (p for interaction = 0.062). Intensive statin treatment reduced CVD risk in the high TG/HDL-C group but not in the low group. In conclusion, a TG/HDL-C index ≥ 2.5 was associated with higher CVD risk in T2DM patients with retinopathy and hyperlipidemia without a history of CVD. The TG/HDL-C index may identify patients who benefit from intensive statin treatment.

  • Sucrose-preferring gut microbes prevent host obesity by producing exopolysaccharides

    Shimizu Hidenori, Miyamoto Junki, Hisa Keiko, Ohue-Kitano Ryuji, Takada Hiromi, Yamano Mayu, Nishida Akari, Sasahara Daiki, Masujima Yuki, Watanabe Keita, Nishikawa Shota, Takahashi Sakura, Ikeda Takako, Nakajima Yuya, Yoshida Naofumi, Matsuzaki Chiaki, Kageyama Takuya, Hayashi Ibuki, Matsuki Akari, Akashi Ryo, Kitahama Seiichi, Ueyama Masako, Murakami Takumi, Inuki Shinsuke, Irie Junichiro, Satoh-Asahara Noriko, Toju Hirokazu, Mori Hiroshi, Nakaoka Shinji, Yamashita Tomoya, Toyoda Atsushi, Yamamoto Kenji, Ohno Hiroaki, Katayama Takane, Itoh Hiroshi, Kimura Ikuo

    Nature Communications (Springer Nature)  16 ( 1 ) 1145 2025.12

    　View Summary

    Commensal bacteria affect host health by producing various metabolites from dietary carbohydrates via bacterial glycometabolism; however, the underlying mechanism of action remains unclear. Here, we identified Streptococcus salivarius as a unique anti-obesity commensal bacterium. We found that S. salivarius may prevent host obesity caused by excess sucrose intake via the exopolysaccharide (EPS) –short-chain fatty acid (SCFA) –carbohydrate metabolic axis in male mice. Healthy human donor-derived S. salivarius produced high EPS levels from sucrose but not from other sugars. S. salivarius abundance was significantly decreased in human donors with obesity compared with that in healthy donors, and the EPS–SCFA bacterial carbohydrate metabolic process was attenuated. Our findings reveal an important mechanism by which host–commensal interactions in glycometabolism affect energy regulation, suggesting an approach for preventing lifestyle-related diseases via prebiotics and probiotics by targeting bacteria and EPS metabolites.

  • 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.

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Reviews, Commentaries, etc. 【 Display / hide 】

  • ニルセビマブのRSウイルス感染による下気道疾患重症化予防効果の比較　単施設での検討(The Preventive Effect of Nirsevimab on RSV-induced Lower Respiratory Tract Disease Severity: A Single-center Study)

    伊藤 裕, 岩島 覚, 本橋 康弘, 古澤 由梨, 早川 晶也, 早野 聡, 關 圭吾, 矢田 宗一郎

    日本小児科学会雑誌 ((公社)日本小児科学会)  129 ( 2 ) 212 - 212 2025.02

    ISSN  0001-6543

  • CASZ1はMRの新規転写抑制因子であり、高血圧や原発性アルドステロン症の発症に関与する

    横田 健一, 柴田 洋孝, 栗原 勲, 伊藤 裕, 曽根 正勝

    日本内分泌学会雑誌 ((一社)日本内分泌学会)  100 ( 5 ) 1629 - 1629 2025.02

    ISSN  0029-0661

  • 健診画像を用いた膵形態的特徴および糖代謝指標の体重増加に伴う経時的変化に関する検討

    稲石 淳, 洲之内 真理愛, 清水 良子, 税所 芳史, 伊藤 裕, 高石 官均, 岩男 泰

    総合健診 ((一社)日本総合健診医学会)  52 ( 1 ) 318 - 318 2025.01

    ISSN  1347-0086

  • Erratum to “Open-Label, Randomized, Controlled, Crossover Trial on the Effect of Dapagliflozin in Patients With ADPKD Receiving Tolvaptan” [Kidney International Reports Volume 10, Issue 4, April 2025, Pages 1063-1075] (Kidney International Reports (2025) 10(4) (1063–1075), (S2468024925000488), (10.1016/j.ekir.2025.01.023))

    Uchiyama K., Kamano D., Nagasaka T., Hama E.Y., Shirai R., Sumura R., Kusahana E., Yanai A., Nakayama T., Kimura T., Takahashi R., Kasai T., Tajima T., Hosoya K., Azegami T., Yamaguchi S., Yoshino J., Ito J., Hayashi M., Kanda T., Ishibashi Y., Washida N., Itoh H., Hayashi K.

    Kidney International Reports  2025

    ISSN  24680249

    　View Summary

    In the original published version of this article, the following errors were introduced during the copyediting process by the Suppliers. The text originally published “In addition, the study initially included only a small number of participants.” Has been corrected to “In addition, the study should initially include a small number of participants.” The text originally published “All data requests are submitted to the corresponding author for consideration.” Has been corrected to “All data requests should be submitted to the corresponding author for consideration.” These errors bear no reflection on the article or its authors. The publisher apologizes to the authors and the readers for this unfortunate error. DOI of original article: https://doi.org/10.1016/j.ekir.2025.01.023

  • 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.

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Presentations 【 Display / hide 】

  • Gut Resilience and Happy Life Expectancy

    Hiroshi Itoh

    2025.06
    , 

    Oral presentation (invited, special)

  • Effects of Exopolysaccharides from Leuconostoc mesenteroides on The Gut Environment and Metabolic Parameters in Humans

    Hiroshi Itoh, Junichiro Irie, Ikuo Kimura

    Postbiotics Conference 2025, 

    2025.03
    , 

    Oral presentation (invited, special)

  • Sustainable Development Goals: Integrating Health, Environment, and Social Justice

    Hiroshi Itoh

    2024.09
    , 

    Oral presentation (invited, special)

  • Glucagon-like peptide 1 (GLP-1) agonists: is there a role for hypertension treatment beyond body weight?

    Hiroshi Itoh

    2024.09

  • SDGs (Sustainable Development Goals) and Hypertension Zero in the era of Anthropocene

    2023.12
    , 

    Oral presentation (invited, special)

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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 】

  • Japanese Society of Hypertension Honorary Award

    2022.10

    Type of Award： Award from Japanese society, conference, symposium, etc.

  • Japanese Society of Endocrinology Award

    2020.06

    Type of Award： Award from Japanese society, conference, symposium, etc.

  • 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

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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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