Elucidation of the mechanism of muscle atrophy in chronic kidney disease from the viewpoint of electrolyte and water balance

• Project/Area Number: 18K16003
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Kagawa University
• Principal Investigator: Yamazaki Daisuke 香川大学, 医学部, 協力研究員 (50814216)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 腎除神経 / 食塩 / 筋委縮 / 体液貯留 / 腎交感神経 / 体液バランス / 老化 / Na / 異化 / サルコペニア / 慢性腎臓病

Outline of Final Research Achievements

In this study, renal denervation was performed in mice to examine the effects of renal sympathetic nerves on fluid balance and muscle atrophy. In young mice, renal denervation decreased urine volume, increased urea production in the liver, and increased total body water content, confirming that renal denervation has a water conservation effect. Renal denervation suppressed the decrease in total body water content observed in aged mice, confirming that renal denervation has a water conservation effect even in aged mice. In the high salt intake model, renal denervation suppressed body weight loss associated with activation of the systemic fluid retention mechanism in the sham group.

Academic Significance and Societal Importance of the Research Achievements

本研究は慢性腎臓病の筋委縮のメカニズムを電解質・体液バランスや交感神経の観点から解明し、新しい筋委縮の予防・治療開発に繋げることを目的とした。
今回の研究結果より、腎除神経は若齢あるいは高齢マウスにおいても体液保持作用を示し、高齢化によって生じる体液量減少や、高食塩摂取に伴う筋肉の異化・体重減少を抑制できることが示唆された。腎交感神経活動が、抗老化や筋委縮の新たな予防・治療標的となる可能性が考えられた。

Research Products

• [Journal Article] Renal sympathetic nerve activity regulates cardiovascular energy expenditure in rats fed high salt (2020)
  • Author(s): Morisawa N, Kitada K, Fujisawa Y, Nakano D, Yamazaki D, Kobuchi S, Li L, Zhang Y, Morikawa T, Konishi Y, Yokoo T, Luft FC, Titze J, Nishiyama A.
  • Journal Title: Hypertension research Volume: Epub Issue: 6 Pages: 482-491
  • DOI: 10.1038/s41440-019-0389-1
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Renal denervation improves the survival rate via a reduction in heart rate in high salt-fed Dahl salt-sensitive rats (2022)
  • Author(s): orisawa Norihiko, Kitada Kento,Fujisawa Yoshihide, Yamazaki Daisuke, Nakano Daisuke, Titze JEns Nishiyama Akira
  • Organizer: The 29th Scientific Meeting of the International Society of Hypertension. Kyoto, Japan. 2022 10.
• [Presentation] 北田研人. 森澤紀彦. 中野大介. Jens T. 西山成. (2020)
  • Author(s): 5/6腎摘に伴う腎尿濃縮力低下と体液喪失は、多臓器の体液保持機構を活性化し、体液貯留・血圧上昇を起こす
  • Organizer: 第63回日本腎臓学会学術総会、横浜
• [Presentation] Renal Denervation Improves the Survival Rate Independent of Blood Pressure in High Salt-Fed Dahl Salt-Sensitive Rats. (2020)
  • Author(s): Norihiko Morisawa, Kento Kitada, Yoshihide Fujisawa, Daisuke Nakano, Daisuke Yamazaki, Jens Titze and Akira Nishiyama.
  • Organizer: 18th Asian Pacific Congress of Nephrology, Hong-Kong.
• [Presentation] Renal denervation prevents high salt induced body weight loss (2018)
  • Author(s): DaisukeYamazaki
  • Organizer: Internal Society of Nephrology Frontiers meeting, Tokyo
  • Int'l Joint Research
• [Presentation] 腎除神経は尿中Na+排泄量とは非依存的に高食塩摂取による体重減少を抑制する (2018)
  • Author(s): 山﨑大輔
  • Organizer: 第61回日本腎臓学会学術総会、新潟
• [Presentation] Renal denervation inhibits high salt-induced body weight loss independently of urinary sodium excretion (2018)
  • Author(s): DaisukeYamazaki
  • Organizer: 18th World Congress of basic and clinical pharmacology, Kyoto
  • Int'l Joint Research
• [Presentation] Renal denervation inhibits high salt-induced body weight loss independently of urinary sodium excretion and liver sympathetic nerve system (2018)
  • Author(s): DaisukeYamazaki
  • Organizer: 第1回四国4大学合同研究発表会, 愛媛