Study of the Sialic Acid Modification and Kdn Accumulation in Acquired Cystic Kidney Disease

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17730
• 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 Tsukuba
• Principal Investigator: Kawanishi Kunio 筑波大学, 医学医療系, 助教 (00578750)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 後天性嚢胞腎 / 後天性嚢胞腎随伴腎細胞癌 / シアル酸 / Kdn / バイオマーカー

Outline of Final Research Achievements

Acquired cystic kidney disease (ACKD), a non-hereditary cystic disease, occurs in kidneys of choronic kidney disease (CKD) patients. The frequency of renal cell carcinoma is 5- to 15-fold higher in hemodialysis patients than in non-hemodialysis patients, and the frequency of acquired cystic kidney-associated renal cell carcinoma (ACD-RCC) is known to increase with the number of years of dialysis. Accoding to the discoveries of deaminoneuraminic acid (Kdn) accumulation in hemodialysis patients, and the presence of anti-Kdn antibodies in human serum, we hypothesized that Kdn is involved in the development of ACKD and ACD-RCC. We established a method to detect Kdn-conjugated glycopeptides in patient tissues and cell cultures. Although we could not find Kdn-conjugated glycopeptides in ACD-RCC tissues, we found several unique sialylated peptides that could be usuful biomarkers for ACD-RCC.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

透析患者のKdn蓄積とヒト血清中に抗Kdn抗体が存在するという発見から、ACKDのACD-RCCへの進展メカニズム解明を目指し、Kdn探索を行った。研究を通して、ACD-RCC組織からKdn型ペプチドを発見することはできなかったが、ヒト細胞株上でKdn型ペプチドを検出する手法を確立できた意義は大きい。また、研究期間中に米国での事前検討を深化させ、脊椎動物が保存するマンノース代謝経路とKdn産生の意義は過剰なマンノースの緩衝機構にあるとする学説を論文化できた。また研究の過程で透析腎癌マーカーとして有力な分子を複数発見し特許出願した社会的意義は大きく、検証のための多施設共同研究を開始できている。