Establishing the diagnosis of acute focal bacterial nephritis in children

• Project/Area Number: 17K10142
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Yamaguchi University
• Principal Investigator: MIZUTANI Makoto 山口大学, 大学院医学系研究科, 助教 (10593303)
• Co-Investigator(Kenkyū-buntansha): 松重 武志 山口大学, 医学部附属病院, 講師 (60528941) ; 長谷川 俊史 山口大学, 大学院医学系研究科, 教授 (90314806)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 小児腎臓 / 上部尿路感染症 / 高サイトカイン血症 / IFN-γ / 急性巣状細菌性腎炎 / インターフェロンγ / 腎瘢痕 / 小児

Outline of Final Research Achievements

We have found that IFN-γ is greatly involved in the pathophysiology of acute focal bacterial nephritis (AFBN), especially the process of inflammation. Pathological analysis of “IFN-γ hyperproduction” in this study. Cytokine measurements showed that sTNFR1 as activation of macrophages was significantly higher in AFBN than in acute pyelonephritis (APN) (4,100 vs. 3,400 pg/mL, p=0.006). It is considered that macrophages are affected by IFN-γ. As a study of the source of IFN-γ production, we have performed a cytokine analysis of intracellular mononuclear cells in peripheral blood, but the identification of the producing cell has not been clarified.

Academic Significance and Societal Importance of the Research Achievements

AFBNの病態解明を進めるべく、本研究を実施した。サイトカイン解析では, AFBN患児においてIFN-γの影響を受けると考えられるマクロファージの活性化を示唆する所見を得た。AFBNが高サイトカイン血症を来す病態が追加証明され, 上部尿路感染症の中で重症病態であることがより明確になった. IFN-γ産生源の検討では，明らかな産生細胞の同定には至らず, 新規治療法の確立とともに今後の研究課題となった．

Research Products

• [Journal Article] Distinctive inflammatory profile between acute focal bacterial nephritis and acute pyelonephritis in children. (2017)
  • Author(s): Mizutani M, Hasegawa S, Matsushige T, Ohta N, Kittaka S, Hoshide M, Kusuda T, Takahashi K, Ichihara K, Ohga S.
  • Journal Title: Cytokine Volume: 99 Pages: 24-29
  • DOI: 10.1016/j.cyto.2017.06.012
  • Peer Reviewed / Open Access
• [Presentation] Distinctive inflammatory profile of acute focal bacterial nephritis compared to acute pyelonephritis in children (2018)
  • Author(s): Makoto Mizutani
  • Organizer: The 9th Asian Congress of Pediatric Infectious Diseases (ACPID 2018)
  • Int'l Joint Research
• [Presentation] Distinctive cytokine profile between acute focal bacterial nephritis and acute pyelonephritis in children (2017)
  • Author(s): Makoto Mizutani
  • Organizer: The 14th Congress of Asian Society for Pediatric Research
  • Int'l Joint Research
• [Presentation] 急性巣状細菌性腎炎のサイトカインプロファイル ～急性腎盂腎炎と比較して～ (2017)
  • Author(s): 水谷 誠
  • Organizer: 第49回日本小児感染症学会