| Project/Area Number |
16K21384
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Kidney internal medicine
Metabolomics
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| Research Institution | Tokai University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 急性腎障害 / 骨ミネラル代謝異常 / FGF23 / 急性腎傷害 |
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| Outline of Final Research Achievements |
FGF23 levels increase rapidly after acute kidney injury (AKI), but the role of FGF23 is largely unknown. We investigated the longitudinal changes in mineral metabolism and FGF23 using a rat ischemia-reperfusion injury (IRI) model, which involved unilateral nephrectomy and 35-min contralateral IRI. Rats with IRI exhibited acute hyperphosphatemia and progressively increasing FGF23 levels, which was accompanied by decreased biosynthesis of 1,25-dihydroxyvitamin D. During renal recovery, the elevated FGF23 levels declined progressively and finally normalized, with the occurrence of hypophosphatemia and increased 1,25-dihydroxyvitamin D levels. Administration of the pan-FGFR inhibitor (PD173074) led to persistent hyperphosphatemia and increased production of 1,25-dihydroxyvitamin D. These results suggest that elevated FGF23 after AKI represents a compensatory response to maintain neutral phosphate balance in a similar, but more rapid and dynamic, manner to that in chronic kidney disease.
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| Academic Significance and Societal Importance of the Research Achievements |
今回の検討結果より，慢性腎臓病のみならず，急性腎障害においても骨ミネラル代謝異常が出現することが示され，さらにこの病態においてFGF23が重要な役割を担っていることが明らかとなった。急性腎障害はさまざまな疾患を背景に発症し，予後に重大な影響を及ぼし，その対策は喫緊の課題である。急性腎障害に伴う骨ミネラル代謝異常は，急性腎障害後の予後悪化にも関与し得る病態であり，本研究成果は急性腎障害後の予後改善を図る上で重要な基盤的理解を提供するものと考えられる。
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