Elucidation of factors contributing to the progression of renal impairment based on single nucleotide polymorphism of uric acid transporter

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08224
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: Ichida Kimiyoshi 東京薬科大学, 薬学部, 教授 (80183169)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: CKD / ABCG2 / 腎機能 / 尿酸トランスポーター / 尿酸 / 一塩基多型

Outline of Final Research Achievements

Hyperuricemia is a risk factor for the development of renal disease or a facilitator of renal impairment, and to clarify the effect of ABCG2 function on the renal function decline, we evaluated the single nucleotide polymorphisms Q126X and Q141K in the ABCG2 gene. In a study of 276 CKD patients, there was a trend toward accelerated eGFR decline with presumed ABCG2 functional decline in the CKD stage G3 group. A retrospective cohort study of 1885 healthy subjects (eGFR >60 mL/min/1.73m2) also showed that estimated ABCG2 functional decline significantly reduced renal function over a longer time course of 9-10 years. Furthermore, the results were similar when matched by propensity score for age, gender (males only), eGFR, BMI, and serum uric acid level, indicating the involvement of ABCG2 in renal function independent of serum uric acid level.

Free Research Field

尿酸代謝

Academic Significance and Societal Importance of the Research Achievements

ABCG2の機能低下が高尿酸血症を引き起こすと同時に、高尿酸血症を介さずにも腎障害の進行を促進することが明らかになった。さらに高尿酸血症に著しいABCG2機能低下を合併すると、腎障害の進行は促進されることも明らかになった。ABCG2の機能低下を来す一塩基多型Q126XとQ141Kの頻度は高いことから、将来的には高尿酸血症患者のABCG2の一塩基多型を調べることにより、より腎障害の進行のリスクの高い患者に絞って、その他のリスクの管理や生活指導を行えるようになることが期待される。