Urinary mulberry bodies as a potential biomarker for early diagnosis and efficacy assessment of enzyme replacement therapy in Fabry nephropathy

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K17742
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Osaka University
• Principal Investigator: Yonishi Hiroaki 大阪大学, 医学部附属病院, 医員 (40822143)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: ファブリー病 / 尿中マルベリー小体 / グロボトリアオシルセラミド / リソソーム / ポドサイト

Outline of Final Research Achievements

【Methods】 Fifty-one Fabry disease (FD) patients were enrolled. Urinary mulberry bodies (uMBs) were immunostained for renal cell markers to determine their origin. The association between semiquantitative uMB excretion and the histological severity of podocyte vacuolation was investigated using the vacuolated podocyte: glomerular average area ratio. The association between the semiquantitative estimate of uMB excretion and duration of ERT was analyzed.
【Results】Thirty-two patients (63%) had uMBs, while only 31% showed proteinuria. The uMBs were positive podocalyxin, suggesting they were derived from podocytes. We observed more severe podocyte vacuolation with increased uMB excretion ;however, the same was not observed with increased proteinuria. The percentage of patients with substantial uMB excretion increased with shorter ERT duration. Eighteenmonth-long ERT reduced uMB excretion without affecting proteinuria.

Free Research Field

腎臓疾患

Academic Significance and Societal Importance of the Research Achievements

尿蛋白や腎機能障害が出現したファブリー病(FD)では、腎病変に対して酵素補充療法(ERT)では充分な治療効果が得られない。FDの腎病変の早期マーカーの確立が求められる中、FD患者に特徴的な尿沈査であるマルベリー小体(MB)に着目し、その臨床的意義について検討した。本研究により尿中MBがポドサイト障害を示し、蛋白尿に先行する早期マーカーであることと、ERTの治療効果の指標となる事明らかにすることができた。