Association between PPI and CYP2C19 in patients with renal failure

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K16012
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Nakashima Akio 東京慈恵会医科大学, 医学部, 助教 (20624688)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 血液透析 / プロトンポンプ阻害剤 / 遺伝子多型

Outline of Final Research Achievements

Proton pump inhibitors are widely used for gastric acid inhibitors and are also used in patients with renal failure including dialysis. CYP2C19 is a gene polymorphism involved in the metabolism of proton pump inhibitors. It is known that the metabolism of proton pump inhibitors differs depending on the polymorphism mainly of CYP2C19 and affects the blood concentration and influences biological functions. The purpose of this study is to clarify the effect of the CYP2C19 gene polymorphism among patients with renal failure including dialysis. Based on our prospective cohort study of hemodialysis patients, we found that the use of proton pump inhibitors was significantly involved in all-cause mortality, infection development, and fractures in patients with renal failure. Both outcomes were higher than those in the non-oral group. It was also suggested that these effects may differ depending on the gene polymorphisms divided into the three groups of CYP2C19.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

本研究ではプロトンポンプ阻害剤による腎不全患者への影響が明らかになった。プロトンポンプ阻害剤の使用により全死亡へのリスクが明示された。またその影響がプロトンポンプ阻害剤の代謝に関与するCYP2C19遺伝子多型により異なる可能性が示唆された。以前よりCYP2C19の遺伝子多型によりプロトンポンプ阻害剤の代謝が異なり血中濃度に影響することが知られているが、全死亡を始めとする副作用に関する報告は少ない。今後、プロトンポンプ阻害剤を使用する際にはCYP2C19などの遺伝子を調べることで、より患者の状態に即した治療を行える可能性があり遺伝子診断を基にした個別化医療への実現につながる可能性がみられた。