Effect of DPP4 inhibitor on cisplatin cytotoxicity to the cancer and kidney

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16184
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Takamasa Iwakura 浜松医科大学, 医学部附属病院, 診療助教 (20771091)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 急性腎障害 / シスプラチン / DPP-4阻害薬 / 低Mg血症

Outline of Final Research Achievements

The renoprotective effect of DPP-4 inhibitors has been confirmed to be independent of the decrease in cisplatin uptake into the kidneys. In addition to the increase in cisplatin uptake into the kidney in hypomagnesemia, it was newly revealed that the renal protective effect of DPP-4 inhibitors was lost under hypomagnesemia.
In rats induced with hypomagnesemia, the level of active GLP-1 concentration was equivalent to that of rats with eumagnesemia. The expression of renal GLP-1 receptors was not observed in the renal tubules under normal conditions or after cisplatin administration, suggesting that the renoprotection of DPP-4 inhibitors was not a direct effect of GLP-1-GLP-1R interaction. Investigation of insulin and insulin-like growth factor (IGF-1) as downstream factors of GLP-1 revealed that hypomagnesemia suggested the induction of insulin/IGF-1 resistance

Free Research Field

急性腎障害

Academic Significance and Societal Importance of the Research Achievements

今回明らかとなった低Mg血症ではDPP-4阻害薬の腎保護効果が消失するという現象は、低Mg血症を補正する意義として従来知られている「シスプラチンの腎毒性を軽減する」ということに「DPP-4阻害薬の腎保護効果を発揮させる」ということを加え得る。
最近先進国では糖尿病患者が増加しており、低血糖リスクの低いDPP-4阻害薬は多くの患者に投与されているが、癌患者（特にシスプラチンを投与する患者）では低Mg血症の割合が多いことから、MgとDPP-4阻害薬を併用することでシスプラチンの腎障害を軽減できる可能性が示唆される。