The role of Ca channels and KV1.3 channels in chronic renal failure and the development of preventive therapy against septic acute renal failure progressing to chronic hemodialysis

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K20079
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Anesthesiology
• Research Institution: Tohoku University
• Principal Investigator: Saito Kazutomo 東北大学, 医学系研究科, 助教 (60770740)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 慢性腎不全 / 敗血症 / KV1.3チャネル / 免疫抑制作用

Outline of Final Research Achievements

In chronic renal failure, it has been reported that cytokine production from inflammatory cells is concerned in the progression of renal fibrosis. Many Kv1.3 channels are expressed in the thymus, which is the main immunity reaction, and the KV1.3 channels may contribute to the progression of chronic renal failure.
In this study, it was revealed that antihistamines exert an immunosuppressive effect by inhibiting the KV1.3 channel. In addition, it was considered that overexpression of KV1.3 channel is recognized in renal fibrosis induced by chronic renal failure, and KV1.3 channels could promote the progression of pathological conditions. It was suggested that antihistamines with KV1.3 channel inhibitory potential have potential to be useful as antifibrotic drugs in chronic renal failure.

Free Research Field

麻酔科学

Academic Significance and Societal Importance of the Research Achievements

第二世代抗ヒスタミン薬であるセチリジン、フェキソフェナジン、アゼラスチン、テルフェナジンなどがリンパ球のKV1.3チャネル電流を効果的に阻害したことから、これらの薬剤が慢性腎不全における腎線維化の治療に有用である可能性が示唆された。今後、腎線維化の病態生理の解明が更に進むとともに、既存の頻用薬がもつ”抗線維化”薬としての有用性・実用性が示され、透析導入や腎移植患者の減少に繋がることが期待される。