Hayashi, Kaori

写真a

Affiliation

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

Position

Assistant Professor/Senior Assistant Professor

Academic Background 【 Display / hide

  • 1998.04
    -
    2004.03

    Keio University School of Medicine

    University, Graduated

  • 2007.04
    -
    2011.03

    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

  • Life Science / Nephrology

 

Papers 【 Display / hide

  • Effects of high glucose and lipotoxicity on diabetic podocytes

    Nakamichi R., Hayashi K., Itoh H.

    Nutrients (Nutrients)  13 ( 1 ) 1 - 11 2021.01

     View Summary

    Glomerular podocytes are highly differentiated cells that cover glomerular capillaries from the outside and have a characteristic morphology with numerous foot processes. The formation of slit membranes between the foot processes serves as a final filtration barrier for urine filtration from the blood. Podocyte damage causes disruption of the slit membrane, subsequent proteinuria and finally glomerulosclerosis, which is a common pathway in various types of chronic kidney disease (CKD). In recent years, there has been an increase in diabetes, due to rapid lifestyle changes, which is the main cause of CKD. Therefore, understanding the effect of diabetic status on podocytes is of great importance to establish a strategy for preventing CKD progression. In this review, we summarize altered glucose and lipid metabolism in diabetic podocytes and also discuss the reversibility of the changes in podocyte phenotype.

  • Association of glomerular DNA damage and DNA methylation with one-year eGFR decline in IgA nephropathy

    Hayashi K., Hishikawa A., Hashiguchi A., Azegami T., Yoshimoto N., Nakamichi R., Tokuyama H., Itoh H.

    Scientific Reports (Scientific Reports)  10 ( 1 )  2020.12

     View Summary

    Accumulation of DNA double-strand breaks (DSBs) is linked to aging and age-related diseases. We recently reported the possible association of DNA DSBs with altered DNA methylation in murine models of kidney disease. However, DSBs and DNA methylation in human kidneys was not adequately investigated. This study was a cross-sectional observational study to evaluate the glomerular DNA DSB marker γH2AX and phosphorylated Ataxia Telangiectasia Mutated (pATM), and the DNA methylation marker 5-methyl cytosine (5mC) by immunostaining, and investigated the association with pathological features and clinical parameters in 29 patients with IgA nephropathy. To evaluate podocyte DSBs, quantitative long-distance PCR of the nephrin gene using laser-microdissected glomerular samples and immunofluorescent double-staining with WT1 and γH2AX were performed. Glomerular γH2AX level was associated with glomerular DNA methylation level in IgA nephropathy. Podocytopathic features were associated with increased number of WT1(+)γH2AX(+) cells and reduced amount of PCR product of the nephrin gene, which indicate podocyte DNA DSBs. Glomerular γH2AX and 5mC levels were significantly associated with the slope of eGFR decline over one year in IgA nephropathy patients using multiple regression analysis adjusted for age, baseline eGFR, amount of proteinuria at biopsy and immunosuppressive therapy after biopsy. Glomerular γH2AX level was associated with DNA methylation level, both of which may be a good predictor of renal outcome in IgA nephropathy.

  • DNA damage and expression of DNA methylation modulators in urine-derived cells of patients with hypertension and diabetes

    Hishikawa A., Hayashi K., Yoshimoto N., Nakamichi R., Homma K., Itoh H.

    Scientific reports (Scientific reports)  10 ( 1 )  2020.02

     View Summary

    Diabetes and hypertension have become the primary causes of chronic kidney disease worldwide. However, there are no established markers for early diagnosis or predicting renal prognosis. Here, we investigated the expression profiles of DNA repair and DNA methylation factors in human urine-derived cells as a possible diagnostic or renal prognosis-predicting marker. A total of 75 subjects, aged 63.3 ± 1.9 years old, were included in this study. DNA and RNA were extracted from 50 mL of urine samples. We evaluated DNA double-strand breaks (DSBs) by the quantitative long distance-PCR method and performed real-time RT-PCR analysis to analyze the expression of renal cell-specific markers, DNA DSB repair factor KAT5, DNA methyltransferases DNMTs, and demethylation enzymes TETs. In patients with hypertension and diabetes, DNA DSBs of the nephrin gene increased with decreased urine KAT5/nephrin expression, consistent with our previous study (Cell Rep 2019). In patients with hypertension, DNA DSBs of the AQP1 gene were increased with elevated urine DNMTs/AQP1 and TETs/AQP1 expression. Moreover, urine DNMTs/AQP1 expression was significantly correlated with the annual eGFR decline rate after adjustment for age, baseline eGFR, the presence of diabetes and the amount of albuminuria, suggesting a possible role as a renal prognosis predictor.

  • DNA Damage Repair and DNA Methylation in the Kidney

    Hayashi K., Hishikawa A., Itoh H.

    American Journal of Nephrology (American Journal of Nephrology)  50 ( 2 ) 81 - 91 2019.07

    ISSN  02508095

     View Summary

    The DNA repair system is essential for the maintenance of genome integrity and is mainly investigated in the areas of aging and cancer. The DNA repair system is strikingly cell-type specific, depending on the expression of DNA repair factors; therefore, different DNA repair systems may exist in each type of kidney cell. Importance of DNA repair in the kidney is suggested by renal phenotypes caused by both genetic mutations in the DNA repair pathway and increased stimuli of DNA damage. Recently, we reported the importance of DNA double-strand break repair in glomerular podocytes and its involvement in the alteration of DNA methylation status, which regulates podocyte phenotypes. In this review, we summarize the roles of the DNA repair system in the kidneys and possible associations with altered kidney DNA methylation, which have been infrequently reported together. Investigations of DNA damage repair and epigenetic changes in the kidneys may achieve a profound understanding of kidney aging and diseases.

  • 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.

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

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

  • 尿中細胞の深層学習・画像解析による腎疾患早期診断方法の開発

    2022.06
    -
    2025.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 挑戦的研究(萌芽), Principal investigator

  • 血球細胞DNAメチル化をターゲットとした慢性腎臓病新規治療戦略の開発

    2022.04
    -
    2025.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 基盤研究(B), Principal investigator

  • 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

    2019.04
    -
    2022.03

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

    2016.04
    -
    2019.03

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

 

Courses Taught 【 Display / hide

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

    2022