Ito, Hiroshi



School of Medicine, Department of Internal Medicine (Nephrology, Endocrinology and Metabolism) (Shinanomachi)



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Profile 【 Display / hide

  •   Educational background & professional experience (in sequence of the latest year) 2015- present President of Japanese Society of Endocrinology 2015-present Vice Director, Center for Supper Centenarian Medical Research ,Keio University 2015-present Senior Investigator, Japan Society for the Promotion of Science 2010-present Vice Director, Center for Integraced Medical Research,Keio University 2006-present Professor and Chairman   Depertment of Endocrinology, Metabolism and Nephrology   Keio University School of Medicine 2002-2006 Associate Professor and Vice Chairman  Department of Medicine and Clinical Science Kyoto University Graduate School of Medicine 2001-2002 Associate Professor 1993-2000 Assistant Professor 1989 Ph.D., Kyoto University School of Medicine 1983 M.D., Kyoto University School of Medicine

Other Affiliation 【 Display / hide

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

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

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

  • Kidney internal medicine

  • Metabolomics

  • Endocrinology

Research Keywords 【 Display / hide

  • metabolism

  • endocrinology

  • diabtes mellitus

  • hypertension


Papers 【 Display / hide

  • Home-based Aerobic Exercise and Resistance Training in Peritoneal Dialysis Patients: A Randomized Controlled Trial

    Uchiyama K., Washida N., Morimoto K., Muraoka K., Kasai T., Yamaki K., Miyashita K., Wakino S., Itoh H.

    Scientific Reports (Scientific Reports)  9 ( 1 )  2019.12

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    © 2019, The Author(s). Potential effects of aerobic and resistance training in peritoneal dialysis (PD) patients have been partially elucidated. We investigated effects of a home-based exercise program on physical functioning and health-related quality of life (HRQOL) in PD patients. Patients were randomly assigned to exercise (n = 24) and usual care (n = 23) groups. The exercise patients performed aerobic exercise thrice weekly and resistance training twice weekly at home for 12 weeks. The usual care patients received no specific intervention. The distance in incremental shuttle walking test significantly improved in the exercise group compared with the usual care group (P = 0.02). Among the HRQOL subscales assessed using the Kidney Disease Quality of Life-Short Form questionnaire, kidney disease component summary (P = 0.03), physical role functioning (P = 0.01), emotional role functioning (P < 0.01), and role/social component summary (P < 0.01) significantly improved in the exercise group. Moreover, serum albumin was significantly maintained in the exercise group (P = 0.03). There were no reported adverse events associated with the intervention. To our knowledge, this is the first randomized controlled trial to indicate the beneficial effects of a 12-week home-based exercise program exclusively in PD patients.

  • Induction of human pluripotent stem cells into kidney tissues by synthetic mRNAs encoding transcription factors

    Hiratsuka K., Monkawa T., Akiyama T., Nakatake Y., Oda M., Goparaju S., Kimura H., Chikazawa-Nohtomi N., Sato S., Ishiguro K., Yamaguchi S., Suzuki S., Morizane R., Ko S., Itoh H., Ko M.

    Scientific Reports (Scientific Reports)  9 ( 1 )  2019.12

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    © 2019, The Author(s). The derivation of kidney tissues from human pluripotent stem cells (hPSCs) and its application for replacement therapy in end-stage renal disease have been widely discussed. Here we report that consecutive transfections of two sets of synthetic mRNAs encoding transcription factors can induce rapid and efficient differentiation of hPSCs into kidney tissues, termed induced nephron-like organoids (iNephLOs). The first set - FIGLA, PITX2, ASCL1 and TFAP2C, differentiated hPSCs into SIX2 + SALL1 + nephron progenitor cells with 92% efficiency within 2 days. Subsequently, the second set - HNF1A, GATA3, GATA1 and EMX2, differentiated these cells into PAX8 + LHX1 + pretubular aggregates in another 2 days. Further culture in both 2-dimensional and 3-dimensional conditions produced iNephLOs containing cells characterized as podocytes, proximal tubules, and distal tubules in an additional 10 days. Global gene expression profiles showed similarities between iNephLOs and the human adult kidney, suggesting possible uses of iNephLOs as in vitro models for kidneys.

  • Hypertension as a Metabolic Disorder and the Novel Role of the Gut

    Tanaka M., Itoh H.

    Current Hypertension Reports (Current Hypertension Reports)  21 ( 8 )  2019.08

    ISSN  15226417

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    © 2019, The Author(s). Purpose of Review: Hypertension is related to impaired metabolic homeostasis and can be regarded as a metabolic disorder. This review presents possible mechanisms by which metabolic disorders increase blood pressure (BP) and discusses the importance of the gut as a novel modulator of BP. Recent Findings: Obesity and high salt intake are major risk factors for hypertension. There is a hypothesis of “salt-induced obesity”; i.e., high salt intake may tie to obesity. Heightened sympathetic nervous system (SNS) activity, especially in the kidney and brain, increases BP in obese patients. Adipokines, including adiponectin and leptin, and renin-angiotensin-aldosterone system (RAAS) contribute to hypertension. Adiponectin induced by a high-salt diet may decrease sodium/glucose cotransporter (SGLT) 2 expression in the kidney, which results in reducing BP. High salt can change secretions of adipokines and RAAS-related components. Evidence has been accumulating linking the gastrointestinal tract to BP. Glucagon-like peptide-1 (GLP-1) and ghrelin decrease BP in both rodents and humans. The sweet taste receptor in enteroendocrine cells increases SGLT1 expression and stimulates sodium/glucose absorption. Roux-en-Y gastric bypass improves glycemic and BP control due to reducing the activity of SGLT1. Na/H exchanger isoform 3 (NHE3) increases BP by stimulating the intestinal absorption of sodium. Gastrin functions as an intestinal sodium taste sensor and inhibits NHE3 activity. Intestinal mineralocorticoid receptors also regulate sodium absorption and BP due to changing ENaC activity. Gastric sensing of sodium induces natriuresis, and gastric distension increases BP. Changes in the composition and function of gut microbiota contribute to hypertension. A high-salt/fat diet may disrupt the gut barrier, which results in systemic inflammation, insulin resistance, and increased BP. Gut microbiota regulates BP by secreting vasoactive hormones and short-chain fatty acids. BP-lowering effects of probiotics and antibiotics have been reported. Bariatric surgery improves metabolic disorders and hypertension due to increasing GLP-1 secretion, decreasing leptin secretion and SNS activity, and changing gut microbiome composition. Strategies targeting the gastrointestinal system may be therapeutic options for improving metabolic abnormalities and reducing BP in humans. Summary: SNS, brain, adipocytes, RAAS, the kidney, the gastrointestinal tract, and microbiota play important roles in regulating BP. Most notably, the gut could be a novel target for treatment of hypertension as a metabolic disorder.

  • Influence of antihypertensive drugs in the subtype diagnosis of primary aldosteronism by adrenal venous sampling

    Nagasawa M., Yamamoto K., Rakugi H., Takeda M., Akasaka H., Umakoshi H., Tsuiki M., Takeda Y., Kurihara I., Itoh H., Ichijo T., Katabami T., Wada N., Shibayama Y., Yoshimoto T., Ogawa Y., Kawashima J., Sone M., Inagaki N., Takahashi K., Fujita M., Watanabe M., Matsuda Y., Kobayashi H., Shibata H., Kamemura K., Otsuki M., Fujii Y., Ogo A., Okamura S., Miyauchi S., Yanase T., Suzuki T., Kawamura T., Naruse M.

    Journal of Hypertension (Journal of Hypertension)  37 ( 7 ) 1493 - 1499 2019.07

    ISSN  02636352

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    © 2019 Wolters Kluwer Health, Inc. All rights reserved. Objectives:Because of the influence on the renin-angiotensin-aldosterone system, it is recommended to avoid, if possible, the use of angiotensin-converting-enzyme inhibitors, angiotensin II type 1 receptor blockers, diuretics, β-blockers, and mineralocorticoid receptor antagonists during the diagnostic period of primary aldosteronism. A laterality index more than 4 in adrenocorticotropic hormone (ACTH)-stimulated adrenal venous sampling (ACTH-AVS) is a widely used classification of the unilateral subtype that can benefit from adrenalectomy. Here, we revealed clinical features of patients taking drugs that could affect the primary aldosteronism diagnosis (DAPD) and investigated whether the classification with laterality index more than 4 in ACTH-AVS is applicable to these patients.Patients and methods:Using a large database of primary aldosteronism patients in Japan, we analyzed 2122 patients with successful ACTH-AVS.Results:Patients who received any DAPD (n = 209) showed higher prevalence of comorbidity burdens and took more antihypertensive drugs compared with patients without DAPD. In patients taking DAPD, those with laterality index more than 4 had a higher prevalence of hypokalemia, a higher aldosterone-to-renin ratio and a higher prevalence of adrenal mass than those with laterality index of 4 or less. Adrenalectomy was performed in 76% patients with laterality index more than 4 and 20% with laterality index of 4 or less. Patients who underwent adrenalectomy showed biochemical cure in 89% with laterality index more than 4 and 50% with laterality index of 4 or less (P = 0.001). Multivariate regression analysis showed that laterality index more than 4 was an independent predictor of a biochemical cure. Biochemical cure rate in patients with laterality index more than 4 was consistently high, irrespective of the potential effect of individual DAPD on laterality index.Conclusion:Our findings suggest that in primary aldosteronism patients to whom DAPD were administrated due to severe clinical features, laterality index more than 4 in ACTH-AVS could accurately predict a biochemical cure after adrenalectomy.

  • Efficacy and safety of esaxerenone (CS-3150) for the treatment of essential hypertension: a phase 2 randomized, placebo-controlled, double-blind study

    Ito S., Itoh H., Rakugi H., Okuda Y., Yamakawa S.

    Journal of Human Hypertension (Journal of Human Hypertension)  33 ( 7 ) 542 - 551 2019.07

    ISSN  09509240

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    © 2019, Springer Nature Limited. This was a phase 2, multicenter, randomized, double-blind, placebo-controlled, open-label comparator study to investigate the efficacy and safety of esaxerenone (CS-3150), a novel non-steroidal mineralocorticoid receptor blocker, in Japanese patients with essential hypertension. Eligible patients (n = 426) received esaxerenone (1.25, 2.5, or 5 mg/day), placebo, or eplerenone (50–100 mg/day) for 12 weeks. The primary efficacy endpoint was the change from baseline in sitting systolic and diastolic blood pressure (BP). Safety endpoints included adverse events and serum K+ elevation. There were significant dose–response reductions in the 2.5 and 5 mg/day esaxerenone groups for sitting BP (both p < 0.001) and 24-h BP (both p < 0.0001) compared with placebo, with a mean (95% confidence interval) change in sitting BP of −7.0 (−9.5 to −4.6)/−3.8 (−5.2 to −2.4) mmHg in the placebo group, and −10.7 (−13.2 to −8.2)/−5.0 (−6.4 to −3.6) mmHg, −14.3 (−16.8 to −11.9)/−7.6 (−9.1 to −6.2) mmHg, and −20.6 (−23.0 to −18.2)/ −10.4 (−11.8 to −9.0) mmHg for the 1.25, 2.5, and 5 mg/day esaxerenone groups, respectively, while the change was −17.4 (−19.9 to −15.0)/−8.5 (−9.9 to −7.1) mmHg for eplerenone. The incidence of adverse events was similar in all treatment groups. Serum K+ levels initially increased in proportion with esaxerenone dose but were stable from week 2 until week 12. Plasma esaxerenone concentration increased in proportion with the dose. In conclusion, esaxerenone is an effective and tolerable treatment option for patients with essential hypertension.

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Papers, etc., Registered in KOARA 【 Display / hide

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Reviews, Commentaries, etc. 【 Display / hide

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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, Panelist (nomination)

  • 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 discourse, seminar, tutorial, course, lecture and others

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

    Itoh Hiroshi

    APSH/ISH Summer School,2017 (Shanghai, China) , 2017.08, Public discourse, seminar, tutorial, course, lecture and others

  • “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 discourse, seminar, tutorial, course, lecture and others

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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


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 伊藤 裕, Grant-in-Aid for Challenging Research (Pioneering), Principal Investigator

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


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 伊藤 裕, 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


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 伊藤 裕, Grant-in-Aid for Challenging Research (Pioneering), Principal Investigator

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


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 伊藤 裕, Grant-in-Aid for Scientific Research (A) , Principal Investigator

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


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 伊藤 裕, 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


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


  • 第18回日本心血管内分泌代謝学会 高峰譲吉賞


  • 第3回抗加齢研究奨励賞(臨床の部)


  • 上原記念生命科学財団 研究助成金


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Courses Taught 【 Display / hide











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Memberships in Academic Societies 【 Display / hide

  • 日本内分泌学会

  • 日本高血圧学会, 

  • 日本内科学会

  • 日本肥満学会, 

  • 日本心血管内分泌代謝学会


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