Urinary mulberry bodies as a potential biomarker for early diagnosis and efficacy assessment of enzyme replacement therapy in Fabry nephropathy
| Project/Area Number |
19K17742
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| 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 / 尿中マルベリー細胞 / グロボトリアオ汁シルセラミド / マルベリー小体 / 尿沈査 / 慢性腎臓病 / 腎障害マーカー |
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| Outline of Research at the Start |
ファブリー病は遺伝的な酵素欠損により、糖脂質が蓄積することで臓器障害をきたす。酵素補充療法は根本的な治療法であるが、臓器障害が進行した状態では治療効果が十分に得られないことが多く、早期発見が重要であるとされている。尿中マルベリー細胞はファブリー病患者に特徴的な尿沈渣成分であり診断につながった報告もある。しかしその起源や本態について不明な部分も多いのが現状である。そこで尿中マルベリー細胞の起源や本態を明らかにし、臨床的意義を明らかにする。
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| 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.
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| 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。
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Report
(3 results)
Research Products
(3 results)
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[Journal Article] Urinary mulberry bodies as a potential biomarker for early diagnosis and efficacy assessment of enzyme replacement therapy in Fabry nephropathy.2020
Author(s)
Yonishi H, Namba-Hamano T, Hamano T, Hotta M, Nakamura J, Sakai S, Minami S, Yamamoto T, Takahashi A, Kobayashi W, Maeda I, Hidaka Y, Takabatake Y, Sakai N, Isaka Y.
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Journal Title
Nephrology Dialysis Transplantation
Volume: Online ahead of print.
Related Report
Peer Reviewed
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[Presentation] Urinary Mulberry Bodies as a Potential Biomarker for Early Diagnosis and Monitoring the Effectiveness of Enzyme Replacement Therapy in Fabry Disease2019
Author(s)
Hiroaki Yonishi, Tomoko Namba-Hamano, Takayuki Hamano, Masaki Hotta, Shinsuke Sakai, Ryuta Fujimura, Satoshi Minami, Takeshi Yamamoto, Atsushi Takahashi, Yoshitsugu Takabatake, Norio Sakai, Yoshitaka Isaka
Organizer
the 56th ERA-EDTA Congress
Related Report
Int'l Joint Research
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