Elucidation of the mechanism of cyclosporine nephropathy and development of biomarkers for early detection of cyclosporine nephropathy

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K19603
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Niigata University
• Principal Investigator: Yamada Takeshi 新潟大学, 医歯学総合病院, 助教 (90601922)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: シクロスポリン腎症 / マクロファージ / ネフローゼ症候群

Outline of Final Research Achievements

Nephrotic syndrome is the most common chronic kidney disease in children. Most patients respond well to steroid therapy. However, many patients relapse and suffer from side effects of steroid. On the other hand, cyclosporine is effective in preventing relapse, but cyclosporine-induced nephrotoxicity is observed in some patients during long-term treatment.
I revealed some mechanisms of cyclosporine-induced nephrotoxicity. Chronic cyclosprine-induced nephrotoxicity is characterized by arteriolopathy and tubulointerstitial lesions. Tubulointerstitial lesions consist of vacuolization of the tubules, focal areas of tubular atrophy, and interstitial fibrosis. The results obtained in this study suggest that M2 alternatively activated macrophages are involved in the interstitial fibrosis and that steroid therapy promotes interstitial fibrosis by activating M2 macrophages.

Free Research Field

小児腎臓病学