| Project/Area Number |
18K14983
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Tokushima Bunri University (2020)
The University of Tokushima (2018-2019) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 医療ビッグデータ / FAERS / 慢性腎臓病 / 急性腎障害 / 慢性腎障害 |
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| Outline of Final Research Achievements |
We investigated the protective effects of an FXa inhibitor against renal tubulointerstitial injury using unilateral ureteral obstruction (UUO) mice (a renal tubulointerstitial fibrosis model) and the Food and Drug Administration Adverse Events Reporting System (FAERS) database. The renal expression levels of FX and the FXa receptors protease-activated receptor(PAR)-1 and PAR-2 were higher in UUO mice than in sham-operated mice. UUO-induced tubulointerstitial fibrosis, extracellular matrix expression, macrophage infiltration and inflammatory molecule upregulation were suppressed in UUO mice treated with the FXa inhibitor edoxaban. In an analysis of the FAERS database, there were significantly fewer reports of tubulointerstitial nephritis for patients treated with FXa inhibitors than for patients not treated with inhibitors. These results suggest that FXa inhibitors exert protective effects against chronic kidney disease by inhibiting tubulointerstitial fibrosis.
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| Academic Significance and Societal Importance of the Research Achievements |
超高齢社会日本において、透析予備軍である慢性腎臓病患者数は1,300万人以上と言われており、慢性腎臓病を惹起・進展させないことは非常に重要なため、慢性腎臓病の病態解明と新規治療法の開発は喫緊の課題である。
本研究では、基礎研究と医療ビッグデータ解析により既存薬であるFXa阻害剤が慢性腎臓病の新規治療候補薬になる可能性を見出した。既存薬であるため、臨床的な安全性が確立されており、新たな副作用のリスクが低いと考えられ、今後の臨床応用が期待される。
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