Kanda, Takeshi



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


Assistant Professor/Senior Assistant Professor

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Research Areas 【 Display / hide

  • Kidney internal medicine


Papers 【 Display / hide

  • Role of Nampt-Sirt6 Axis in Renal Proximal Tubules in Extracellular Matrix Deposition in Diabetic Nephropathy

    Muraoka H., Hasegawa K., Sakamaki Y., Minakuchi H., Kawaguchi T., Yasuda I., Kanda T., Tokuyama H., Wakino S., Itoh H.

    Cell Reports (Cell Reports)  27 ( 1 ) 199 - 212.e5 2019.04

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    © 2019 The Author(s) Nicotinamide adenine dinucleotide (NAD + ) metabolism plays a critical role in kidneys. We previously reported that decreased secretion of a NAD + precursor, nicotinamide mononucleotide (NMN), from proximal tubules (PTs) can trigger diabetic albuminuria. In the present study, we investigated the role of NMN-producing enzyme nicotinamide phosphoribosyltransferase (Nampt) in diabetic nephropathy. The expression of Nampt in PTs was downregulated in streptozotocin (STZ)-treated diabetic mice when they exhibited albuminuria. This albuminuria was ameliorated in PT-specific Nampt-overexpressing transgenic (TG) mice. PT-specific Nampt-conditional knockout (Nampt CKO) mice exhibited TBM thickening and collagen deposition, which were associated with the upregulation of the profibrogenic gene TIMP-1. Nampt CKO mice also exhibited the downregulation of sirtuins, particularly in Sirt6. PT-specific Sirt6-knockout mice exhibited enhanced fibrotic phenotype resembling that of Nampt CKO mice with increased Timp1 expression. In conclusion, the Nampt-Sirt6 axis in PTs serves as a key player in fibrogenic extracellular matrix remodeling in diabetic nephropathy. Muraoka et al. reveal that the Nampt-Sirt6 axis in proximal tubules serves as a key player in fibrogenic extracellular matrix remodeling in diabetic nephropathy.

  • 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.

  • Features of and preventive measures against hypertension in the young

    Kawabe H., Azegami T., Takeda A., Kanda T., Saito I., Saruta T., Hirose H.

    Hypertension Research (Hypertension Research)   2019

    ISSN  09169636

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    © 2019, The Author(s). The Japanese hypertension guidelines report that essential hypertension is detected in 1–3% of upper elementary and high school students during blood pressure (BP) screenings. Hypertension in these age groups is an emerging public health concern mainly attributed to the rising rate of pediatric obesity. Considering the existence of BP tracking phenomenon, early preventive education and instruction are necessary, especially for male students with moderately elevated BP showing a tendency toward obesity, despite the low prevalence of hypertension in high school students. Students with a positive family history of hypertension and those born with low birth weight need the same measures. Lifestyle habits, such as increased alcohol intake, dramatically change once students begin university; thus, early education and instruction regarding the factors influencing BP are necessary. In particular, for male students with higher BP during high school, caution regarding increased body weight is required irrespective of their level of obesity. Young adults aged <40 years should be educated about the association between body weight and hypertension. Particular caution surrounding lifestyle habits, including drinking and smoking, is warranted in male hypertensive subjects because hypertension at a young age is strongly associated with obesity. BP monitoring and the management of obesity should be considered efficient approaches to the detection and treatment of hypertension. For the lifetime prevention of hypertension, it is essential to be aware of one’s health status and learn about healthy lifestyles beginning in childhood. BP measurement may be an appropriate means to achieve this goal.

  • β-hydroxybutyrate attenuates renal ischemia-reperfusion injury through its anti-pyroptotic effects

    Tajima T., Yoshifuji A., Matsui A., Itoh T., Uchiyama K., Kanda T., Tokuyama H., Wakino S., Itoh H.

    Kidney International (Kidney International)   2019

    ISSN  00852538

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    © 2019 International Society of Nephrology Ketone bodies including β-hydroxybutyrate (β-OHB) have been shown to protect against ischemic tissue injury when present at low concentrations. We evaluated the impact of β-OHB on renal ischemia/reperfusion injury (IRI). Mice were treated with a continuous infusion of β-OHB using an osmotic mini-pump before and after IRI. We also tested the effects of increasing endogenous serum β-OHB levels by fasting. Renal IRI was attenuated by β-OHB treatment compared to saline control, with similar results in the fasting condition. β-OHB treatment reduced the number of terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling (TUNEL)-positive cells and increased expression of forkhead transcription factor O3 (FOXO3), an upstream regulator of pyroptosis. Although β-OHB treatment did not impact markers of apoptosis, it decreased the expression of caspase-1 and proinflammatory cytokines, indicating that β-OHB blocked pyroptosis. In a human proximal tubular cell line exposed to hypoxia and reoxygenation, β-OHB reduced cell death in a FOXO3-dependent fashion. Histone acetylation was decreased in kidneys exposed to IRI and in proximal tubular cells exposed to hypoxia and reoxygenation, and this effect was ameliorated by β-OHB through the inactivation of histone deacetylases. In vitro, β-OHB treatment restored histone acetylation at the FOXO3 promoter. Consistent with epigenetic molecular effects, the renoprotective effects of β-OHB were still observed when the continuous infusion was stopped at the time of IRI. Thus, β-OHB attenuates renal IRI through anti-pyroptotic effects, likely mediated by an epigenetic effect on FOXO3 expression.

  • High Basolateral Glucose Increases Sodium-Glucose Cotransporter 2 and Reduces Sirtuin-1 in Renal Tubules through Glucose Transporter-2 Detection

    Umino H., Hasegawa K., Minakuchi H., Muraoka H., Kawaguchi T., Kanda T., Tokuyama H., Wakino S., Itoh H.

    Scientific Reports (Scientific Reports)  8 ( 1 )  2018.12

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    © 2018 The Author(s). Under diabetic conditions, sodium-glucose cotransporter 2 (SGLT2) for glucose uptake in proximal tubules (PTs) increases, whereas NAD+-dependent protein deacetylase silent mating type information regulation 2 homolog 1 (Sirtuin-1; SIRT1) for PT survival decreases. Therefore, we hypothesized that increased glucose influx by SGLT2 reduces SIRT1 expression. To test this hypothesis, db/db mice with diabetes and high-glucose (HG)-cultured porcine PT LLC-PK1 cells in a two-chamber system were treated with the SGLT2 inhibitor canagliflozin. We also examined SIRT1 and SGLT2 expression in human kidney biopsies. In db/db mice, SGLT2 expression increased with concomitant decreases in SIRT1, but was inhibited by canagliflozin. For determination of the polarity of SGLT2 and SIRT1 expression, LLC-PK1 cells were seeded into Transwell chambers (pore size, 0.4 μm; Becton Dickinson, Oxford, UK). HG medium was added to either or to both of the upper and lower chambers, which corresponded to the apical and basolateral sides of the cells, respectively. In this system, the lower chamber with HG showed increased SGLT2 and decreased SIRT1 expression. Canagliflozin reversed HG-induced SIRT1 downregulation. Gene silencing and inhibitors for glucose transporter 2 (GLUT2) blocked HG-induced SGLT2 expression upregulation. Gene silencing for the hepatic nuclear factor-1α (HNF-1α), whose nuclear translocation was enhanced by HG, blocked HG-induced SGLT2 expression upregulation. Similarly, gene silencing for importin-α1, a chaperone protein bound to GLUT2, blocked HG-induced HNF-1α nuclear translocation and SGLT2 expression upregulation. In human kidney, SIRT1 immunostaining was negatively correlated with SGLT2 immunostaining. Thus, under diabetic conditions, SIRT1 expression in PTs was downregulated by an increase in SGLT2 expression, which was stimulated by basolateral HG through activation of the GLUT2/importin-α1/HNF-1α pathway.

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

Presentations 【 Display / hide

  • アンジオテンシン抑制による蛋白尿減少作用の経時的比較検討

    Hayashi Kouichi,Honma Kouichirou,Kanda Takeshi,Saruta Takao

    第22回日本臨床薬理学会総会, 2001.12

  • 食塩感受性ラットの腎微小循環における酸化ストレスの役割

    Kanda Takeshi,Hayashi Kouichi,Honma Kouichirou,Ozawa Yuri,Ookubo Ken,Takamatsu Ichirou,Tatematsu Satoru,Saruta Takao

    第5回日本心血管内分泌代謝学会総会, 2001.11

  • Role of T-type calcium channels as a determinant of glomerular microcirculation and subsequent renal protection

    Kanda Takeshi, Hayashi Koichi, Ozawa Yuri, Nagahama Takahiko, Homma Koichiro, Tokuyama Hirobumi, Okubo Ken, Takamatsu Ichiro, Saruta Takao

    Annual Meeting of American Society of Nephrology (34th ; 2001 ; San Francisco, CA, USA), 2001.10

  • T型ならびにL型カルシウム拮抗薬の腎保護作用と微小循環作用との直接的検討

    Kanda Takeshi,Hayashi Kouichi,Honma Kouichirou,Tokuyama Hirobumi,Ookubo Ken,Takamatsu Ichirou,Nagahama Takahiko,Saruta Takao

    第24回日本高血圧学会総会, 2001.10

  • Altered contribution of T-type calcium channels in afferent but not efferent arterioles in SHR

    Homma Koichiro, Hayashi Koichi, Nagahama Takahiko, Kanda Takeshi, Okubo Ken, Takamatsu Ichiro, Tetematsu Satoru, Saruta Takao

    Annual Meeting of American Society of Nephrology (34th ; 2001 ; San Francisco, CA, USA), 2001.10

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

  • 慢性腎臓病の動脈硬化進展におけるNAD代謝産物の役割


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 神田 武志, Grant-in-Aid for Scientific Research (C), Principal Investigator

  • 内分泌ホルモンによる内皮機能に基づいた脂肪機能制御


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 神田 武志, Grant-in-Aid for Scientific Research (C), Principal Investigator


Courses Taught 【 Display / hide











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Memberships in Academic Societies 【 Display / hide

  • 内分泌学会

  • 内科学会

  • 腎臓病学会

  • 高血圧学会