Elucidation the pathophysiology of heat-stress induced CKD

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08607
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Nagoya University
• Principal Investigator: Sato Yuka 名古屋大学, 医学部附属病院, 病院助教 (60846864)
• Co-Investigator(Kenkyū-buntansha): 石本 卓嗣 愛知医科大学, 医学部, 教授 (00534835) ; 前田 佳哉輔 名古屋大学, 医学部附属病院, 助教 (00836306) ; 小杉 智規 名古屋大学, 医学系研究科, 准教授 (90584681)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: CKD / 細胞老化 / 昇熱ストレス / 老化

Outline of Final Research Achievements

Heat stress can develop kidney injury. The evidence indicates that heat stress is the cause of ‘CKD of unknow origin’ reported from Central America (CKDu). In Japan, it is reported that blood pressure drop in summer caused AKI and developed CKD. We previously demonstrated short term-repeated heat stress directly induced kidney injury with animal models. In this study, we examined CKD exposed long-term heat stress by breading mice in the temperature-controlled chamber. We also addressed the relation between heat stress and senescence. C58BL/6 mice were exposed 38℃ environment temperature for 6 hours every day for 6 month. Elderly mice developed chronic kidney failure, while young mice were not decreased renal function. However, p16, which regulated cell cycle arrest and is observed senescence cells, were increased and FOXO3, senescence suppressed gene, were decreased even in young mice Thus, heat stress may cause renal tubular cell senescence which led to irreversible kidney injury.

Free Research Field

腎臓内科

Academic Significance and Societal Importance of the Research Achievements

地球温暖化の影響で、昇熱ストレスによる腎障害は、今後世界の広い地域で問題化することが予想されており、日本も例外ではない。高齢者は熱中症に罹患しやすく重症化しやすいことがわかっており、熱中症による急性腎障害は脱水や横紋筋融解症が主たる原因とされてきた。が、本研究により繰り返す熱暴露が、脱水や横紋筋融解症とは独立して腎障害をもたらし、慢性腎不全に進展することを証明した。また、若年個体でも昇熱ストレスが早期から尿細管細胞の細胞老化の原因となり、CKDを進行させることを示した。