Long-term prognosis of aquaporin-defined responders for tolvaptan in heart failure and renal dysfunction
| Project/Area Number |
15K09065
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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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| Research Field |
Cardiovascular medicine
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| Research Institution | University of Toyama |
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Principal Investigator |
Kinugawa Koichiro 富山大学, 大学院医学薬学研究部(医学), 教授 (00345216)
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| Co-Investigator(Kenkyū-buntansha) |
今村 輝彦 東京大学, 医学部附属病院, 助教 (80746652)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | aqauporin 2 / responders / tolvaptan / renal dysfunction / aquaporin 2 / heart failure / responder / 心腎連関 / アクアポリン２ / トルバプタン / 心不全 / 腎機能障害 / アクアポリン |
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| Outline of Final Research Achievements |
In the real world clinic, almost all heart failure patients were responders to tolvaptan. In sharp contrast to the previous study, there were a considerable population who had a bad prognosis after long-term administration of tolvaptan in spite of responders. Acute response could be predicted by the ratio of urine AQP2 over plasma AVP >0.5x10^3. but prognostic impact of tolvaptan might need higher ratio of urine AQP2 over plasma AVP. Multivariate analysis revealed that most potent independent risk factor for prognosis was eGFR. Considering that lower eGFR would be associated with lower ratio of urine AQP2 over plasma AVP, those who had a certain level of renal dysfunction might not receive benefit from long-term tolvaptan administration in terms of avoiding re-hospitalizations.
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| Academic Significance and Societal Importance of the Research Achievements |
高齢者やHFpEFの多い一般的な心不全コホートではトルバプタンのノンレスポンダーはほとんど存在しないことが分かった．その一方で腎機能eGFRで４０以下に低下した場合にはトルバプタンの長期継続投与による入院回避効果が少なくなると考えられる．かなり心不全ステージの早期からトルバプタンを併用する必要性がありそうである．腎機能障害と尿中AQP2の低下は以前から指摘している通りであるが，その正確なメカニズムについては引き続き検討が必要と考えられる．
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Report
(5 results)
Research Products
(12 results)
