Association of amino acids in autosomal dominant polycystic kidney disease progression

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08603
• 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: Hokkaido University
• Principal Investigator: Nishio Saori 北海道大学, 大学病院, 講師 (90463736)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 常染色体顕性多発性嚢胞腎 / アミノ酸 / LAT1 / トルバプタン

Outline of Final Research Achievements

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder characterized by progressive cyst formation in the kidneys, resulting in bilateral renal enlargement, structural damage and kidney failure. The purpose of this study was to elucidate the involvement of amino acids in the progression of ADPKD and to develop new therapeutic agents. L-type amino acid transporter 1 (LAT1) is one of the transmembrane proteins to deliver essential amino acids. Analysis of Pkd1 and LAT1 double knockout mice accelerated cyst formation via amino acids sensing mechanism. However, appropriate suppression of amino acids by drugs suppresses cyst progression.
We found LAT1 inhibitor ameliorates cystogenesis. Furthermore, we found that the combination of LAT1 inhibitor and tolvaptan inhibits the progression of cysts. These treatments may become new treatments in the future.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

ADPKDは遺伝性腎疾患でも最も多く60歳までに約半数が末期腎不全に至る疾患である。治療薬は現在トルバプタンのみであるが、多飲・多尿などの副作用があり、新たな治療薬の開発が急務である。本研究でアミノ酸吸収を阻害することが治療に結びつき、かつトルバプタン併用で治療効果が増強することを明らかにした。この結果から新規治療薬の開発に繋がる可能性がある。