Hayashi, Kaori



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



Academic Background 【 Display / hide

  • 1998.04

    Keio University School of Medicine

    University, Graduated

  • 2007.04

    Keio University School of Medicine

    Graduate School, Graduated, Doctoral course

Academic Degrees 【 Display / hide

  • 博士(医学), Keio University, Coursework, 2011.03

Licenses and Qualifications 【 Display / hide

  • 日本透析学会専門医

  • 日本高血圧学会専門医・指導医

  • 日本腎臓学会専門医・指導医

  • 日本内科学会総合内科専門医


Research Areas 【 Display / hide

  • Kidney internal medicine


Papers 【 Display / hide

  • Pre-emptive medicine for hypertension and its prospects

    Itoh H., Hayashi K., Miyashita K.

    Hypertension Research (Hypertension Research)  42 ( 3 ) 301 - 305 2019.03

    ISSN  09169636

     View Summary

    © 2018, The Japanese Society of Hypertension. Pre-emptive medicine is a novel medical concept proposed in Japan that aims to precisely predict the onset and progression of diseases and to provide therapeutic interventions during early stages, before symptoms appear. The concept of pre-emptive medicine considers the time-course of a disease in each individual and seeks medical interventions to prevent disease progression. Suitable and promising targets for pre-emptive medicine are non-communicable diseases, including hypertension. Recent advances in genomic analysis, information technology, and artificial intelligence should make this medical concept feasible in the near future. In this review, we focused on pre-emptive medicine for hypertension, referring to concrete plans for the future direction of this research. The ultimate goal of pre-emptive medicine is to completely prevent the onset and progression of hypertension by precisely predicting the elevation of blood pressure and performing interventions to avoid it. The diagnostic processes of hypertension, from the standpoint of pre-emptive medicine, should include the detection of abnormal blood pressure regulation as the earliest manifestation of the disease, the depiction of the present status of hypertension in an individual (“nowcasting”), and a prediction of the future trajectory of the disease (“forecasting”). Novel therapeutic strategies for hypertension, from the standpoint of pre-emptive medicine, should aim for the regression of hypertension through early treatments and the remission of hypertension through intermittent intensive therapies. An efficient modification of lifestyle and therapies, according to the progression of hypertension, should be required. If pre-emptive medicine for hypertension becomes established, it would greatly contribute to the extension of a healthy lifespan, which cannot yet be satisfactorily achieved.

  • Decreased KAT5 Expression Impairs DNA Repair and Induces Altered DNA Methylation in Kidney Podocytes

    Hishikawa A., Hayashi K., Abe T., Kaneko M., Yokoi H., Azegami T., Nakamura M., Yoshimoto N., Kanda T., Sakamaki Y., Itoh H.

    Cell Reports (Cell Reports)  26 ( 5 ) 1318 - 1332.e4 2019.01

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    © 2019 The Author(s) Hishikawa et al. reveal that KAT5-mediated DNA repair is essential for podocyte maintenance and is related to changes in DNA methylation status. Decreased podocyte KAT5 expression may contribute to the pathophysiology of diabetic nephropathy, suggesting a therapeutic target.

  • Transcription Factors as Therapeutic Targets in Chronic Kidney Disease

    Hishikawa, A., Hayashi, K. and Itoh, H.

    Molecules (Molecules)  23 ( 5 )  2018.05

    ISSN  1420-3049

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    The growing number of patients with chronic kidney disease (CKD) is recognized as an emerging problem worldwide. Recent studies have indicated that deregulation of transcription factors is associated with the onset or progression of kidney disease. Several clinical trials indicated that regression of CKD may be feasible via activation of the transcription factor nuclear factor erythroid-2 related factor 2 (Nrf2), which suggests that transcription factors may be potential drug targets for CKD. Agents stabilizing hypoxia-inducible factor (HIF), which may be beneficial for renal anemia and renal protection, are also now under clinical trial. Recently, we have reported that the transcription factor Kruppel-like factor 4 (KLF4) regulates the glomerular podocyte epigenome, and that the antiproteinuric effect of the renin(-)angiotensin system blockade may be partially mediated by KLF4. KLF4 is one of the Yamanaka factors that induces iPS cells and is reported to be involved in epigenetic remodeling. In this article, we summarize the transcription factors associated with CKD and particularly focus on the possibility of transcription factors being novel drug targets for CKD through epigenetic modulation.

  • Intranasal vaccination against angiotensin II type 1 receptor and pneumococcal surface protein A attenuates hypertension and pneumococcal infection in rodents

    Azegami, T., Yuki, Y., Hayashi, K., Hishikawa, A., Sawada, S. I., Ishige, K., Akiyoshi, K., Kiyono, H. and Itoh, H.

    J Hypertens (Journal of Hypertension)  36 ( 2 ) 387 - 394 2018.02

    ISSN  1473-5598

     View Summary

    OBJECTIVES: To combat global increases in the prevalence of lifestyle-related diseases and concomitant infectious diseases, we aimed to develop an innovative intranasal vaccine that simultaneously targets both hypertension and pneumonia, is not given by invasive injection, and offers prolonged therapeutic effect and reduced frequency of administration. METHODS: Angiotensin II type 1 receptor-pneumococcal surface protein A (AT1R-PspA) vaccine, consisting of a cationic nanometer-sized hydrogel incorporating AT1R partial peptide conjugated with PspA and cyclic diguanylate monophosphate adjuvant, was created and given intranasally to spontaneously hypertensive rats (SHRs). Antigen-specific antibodies and blood pressure were examined to evaluate immune responses and the antihypertensive effect of the vaccine. To examine the protective effect of antibodies induced by vaccination on pneumococcal infection, sera obtained from immunized SHRs were incubated with a lethal dose of Streptococcus pneumoniae and then administered to mice. RESULTS: Five doses of AT1R-PspA nasal-vaccine-induced AT1R-specific serum IgG antibody production and attenuated the development of hypertension in SHRs in the long term. Both in-vitro and in-vivo studies revealed that responses to angiotensin II were suppressed in vaccinated rats. Mice passively immunized with sera obtained from AT1R-PspA-vaccinated SHRs were protected from lethal pneumococcal infection. CONCLUSION: Intranasal immunization with AT1R-PspA vaccine has the potential to simultaneously attenuate the development of hypertension and protect from lethal pneumococcal infection.

  • Investigation of Metabolic Factors Associated with eGFR Decline Over 1 Year in a Japanese Population without CKD

    Hayashi, K., Takayama, M., Abe, T., Kanda, T., Hirose, H., Shimizu-Hirota, R., Shiomi, E., Iwao, Y. and Itoh, H.

    J Atheroscler Thromb 24 ( 8 ) 863 - 875 2017.08

    ISSN  1880-3873

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    AIM: Early intervention before the progression of chronic kidney disease (CKD) is essential to prevent end-stage renal disease (ESRD) and cardiovascular complications. This study evaluated the correlation between metabolic and lifestyle-related factors and the decline of estimated glomerular filtration rate (eGFR) over 1 year in a Japanese population without CKD. METHODS: Subjects who received two consecutive annual health checkups from 2013 to 2015 were involved. Factors associated with eGFR decline were identified using multiple regression models. RESULTS: A total of 2531 subjects aged 58.9+/-11.7 years old were included in this study. Baseline levels of HDL-C and ApoA1 correlated with the eGFR decline over 1 year defined as eGFR reduction rate of 15% or more and/or eGFR at the next year 60 ml/min/m(2) (odds ratio (OR) 0.87 (per 10 mg/dl); 95% CI, 0.80-0.94; p=0.0012, 0.90 (per 10 mg/dl); 0.86-0.96; p=0.0004, respectively). A U-shaped relationship between the eGFR decline and HDL-C or ApoA1 levels was not observed in non-CKD population of this study. Metabolic syndrome was significantly associated with eGFR decline (OR 1.32; 1.04-1.67; p=0.0205), although obesity-related factors did not show a significant correlation with eGFR decline over 1 year. CONCLUSION: Low HDL-C and ApoA1 levels significantly correlated with eGFR decline in a short period of 1 year. Metabolic syndrome also showed a significant association with eGFR decline. This study suggests the importance of hypertension and low HDL-C in the metabolic syndrome effect on eGFR decline rather than obesity in non-CKD population.

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

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

  • 腎糸球体ポドサイトにおけるDNA損傷およびエピゲノム変化と腎老化の関連


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 林 香, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • ポドサイトにおけるアンジオテンシン阻害薬によるエピゲノム修復効果の検討


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 林 香, Grant-in-Aid for Young Scientists (B), Principal Investigator