Study on biomarker of kidney injury therapy and its regulation mechanism
| Project/Area Number |
19K08682
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | University of Shizuoka |
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Principal Investigator |
Mori Kiyoshi 静岡県立大学, 薬学部, 特任教授 (60343232)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 急性腎障害 / バイオマーカー / NGAL / リポカリン / 鉄 / 褐色脂肪 / 脱水 / 肥満 |
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| Outline of Research at the Start |
急性腎障害(acute kidney injury, AKI)は透析導入や死亡に至る可能性を有するが、AKIに確実に有効な治療法は実在しない。尿中neutrophil gelatinase-associated lipocalinとliver-type fatty acid binding proteinがAKIの早期診断を可能とするバイオマーカーとして国内保険収載されているが、AKI早期診断後にどのように治療介入へ反映させるのかについては未だ十分な臨床研究が行われていない。本研究ではバイオマーカーによる腎障害介入の効果判定、及びバイオマーカーの発現調節と生物作用に関する多面的研究を推進する。
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| Outline of Final Research Achievements |
Neutrophil gelatinase-associated lipocalin (NGAL) is an iron carrier protein whose circulating level is increased by kidney injury, bacterial infection and obesity, but its metabolic consequence remains elusive. To clarify the physiological role of NGAL in energy homeostasis, wild-type and NGAL-deficient mice were subjected to a high-fat diet or cold exposure. NGAL-deficient mice showed exhibited larger brown adipose tissues (BAT) and gained less body weights as compared to WT mice. These data suggest that endogenous NGAL negatively regulated the sympathetic nervous system and thermogenesis. When exposed to cold condition, KO mice showed higher body temperature and more intense 18F-fluorodeoxyglucose uptake in BAT, which were cancelled by adrenergic receptor blocker. These results suggest that NGAL possesses anti-thermogenic effects through inhibition of BAT activity.
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| Academic Significance and Societal Importance of the Research Achievements |
以上の結果より、NGALは交感神経の制御によりエネルギー代謝を抑制的に働いていることが考えられる。さらに尿中NGALについて、脳外科手術後、突然発症した急性膵炎による乏尿性AKIにおいても、早期の尿中NGAL上昇は軽度で、腎実質性AKIを除外し大量輸液を行う判断に有用であった症例や、また免疫チェックポイント阻害薬を用いたがん治療を行った場合に、副作用として急性尿細管間質性腎炎が起こるこの病態において、尿中NGALが上昇し、ステロイド治療により低下した2症例について報告しており、臨床におけるNGALの意義を示唆している。
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Report
(4 results)
Research Products
(35 results)
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[Journal Article] Cilastatin Ameliorates Rhabdomyolysis-induced AKI in Mice2021
Author(s)
Matsushita Katsuyuki、Mori Kiyoshi、Saritas Turgay、Eiwaz Mahaba B.、Funahashi Yoshio、Nickerson Megan N.、Hebert Jessica F.、Munhall Adam C.、McCormick James A.、Yanagita Motoko、Hutchens Michael P.
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Journal Title
Journal of the American Society of Nephrology
Volume: 32
Issue: 10
Pages: 2579-2594
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] •A CASE OF EGPA THAT DEVELOPED DURING REMISSION OF IGA NEPHROPATHY2021
Author(s)
Yu Soma, Kiyoshi Mori, Yu Noguchi, Shota Kimura, Yuichi Fujiwara, Yoshihiro Yamamoto, Yuuki Itou, Takao Okawa, Masaaki Murakami, Ken Matsuo, Satoshi Tanaka, Noriko Mori, Akira Sugawara
Organizer
International Society of Nephrology, The World Congress of Nephrology 2021
Related Report
Int'l Joint Research
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