Development of a new treatment for chronic kidney disease with beta-hydroxybutyrate, a ketone body

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17735
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: University of Fukui
• Principal Investigator: Kobayashi Mamiko 福井大学, 学術研究院医学系部門(附属病院部), 特命助教 (30791991)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: βヒドロキシ酪酸 / シスプラチン腎症

Outline of Final Research Achievements

We focused on the renoprotective effects of β hydroxybutyrate (βOHB), a ketone body. In cultured human renal tubular cells (HRCE), βOHB inhibited cisplatin-induced apoptosis. We found that Akt, a survival signaling pathway, was associated with the cytoprotective effect of βOHB. Intraperitoneal administration of βOHB significantly decreased elevated serum Cr and BUN levels in a mouse model of cisplatin nephropathy. Furthermore, cisplatin-induced increase in cleaved caspase3 expression was significantly suppressed by βOHB. These results suggest that βOHB has an inhibitory effect on apoptosis in a mouse model of renal injury.

Free Research Field

腎臓内科

Academic Significance and Societal Importance of the Research Achievements

βOHBがAktのリン酸化を介してアポトーシス抑制作用を有し，腎保護作用を発揮する可能性を示すことができた．βOHBは低糖質ダイエットやSGLT2阻害剤で誘導されることが報告されており，今後，腎臓病に対する新規治療法の一つとなる可能性を考える．