ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005


The Latest on Twitter

Kidney Week

Abstract: TH-OR115

Mizoribine Prevents M2-Type Macrophage-Mediated Development of Chronic Lesions in Childhood IgA Nephropathy

Session Information

  • Mostly IgA Nephropathy
    November 07, 2019 | Location: Ballroom C, Walter E. Washington Convention Center
    Abstract Time: 05:54 PM - 06:06 PM

Category: Glomerular Diseases

  • 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix


  • Ikezumi, Yohei, Fujita Health University School of Medicine, Toyoake, Japan
  • Matsumoto, Yuji, Fujita Health University School of Medicine, Toyoake, Japan
  • Kondo, Tomomi, Fujita Health University School of Medicine, Toyoake, Japan
  • Kumagai, Naonori, Fujita Health University School of Medicine, Toyoake, Japan
  • Yamada, Takeshi, Niigata University Medical and Dental Hospital, Niigata, Japan
  • Hasegawa, Hiroya, Niigata University Medical and Dental Hospital, Niigata, Japan
  • Nikolic-Paterson, David J., Monash Medical Centre, Clayton, Victoria, Australia

We have previously reported that CD163+ M2-type macrophages (MQ) are associated with the development of chronic lesions such as glomerular matrix expansion and interstitial fibrosis in the progression of IgA nephropathy (IgAN). On the other hand, the immunosuppressant mizoribine (Miz) has been shown to reduce the progression of childhood IgAN. To investigate the mechanism of Miz protection, we examined the effect of Miz on MQ function.


A total of 73 children with IgAN were divided into groups treated with prednisolone (PSL) only (P group; n=33) or PSL plus Miz (PM group; n=40), and their clinicopathological findings compared retrospectively. For in vitro studies, normal human monocyte-derived MQ were incubated with dexamethasone (Dex), or Dex plus Miz, for 48 hours and then analysed by DNA microarray.


There were no differences in clinical and histological findings at the first (diagnostic) biopsy between the P and PM groups. Although there was no significant difference in the urinary findings, the protocol biopsy after 2-years of treatment showed that the number of sclerotic glomeruli, the degree of interstitial fibrosis, and the number of interstitial CD163+ MQ were significantly reduced in the PM group, but not in the P group. Dex stimulation of cultured human MQ induced up-regulation of scavenger receptor characteristic of M2-type MQ (CD163). Dex also induced up-regulation of cytokines and growth factors associated with inflammation and fibrosis (CCL13, CXCL12, NOS1, NOS2, FGF-8, FGF-21 and CTGF) which was prevented by Miz. In addition, Miz inhibited expression of CD300e, an activating receptor capable of providing survival signals to prevent monocyte apoptosis and to regulate the innate immune response. Immunohistochemistry revealed expression of CD300e which co-localized with CD163+ MQ in biopsies from IgAN patients treated with steroid which was reduced by Miz treatment.


Our data suggest that Miz suppresses M2-type MQ mediated interstitial fibrosis by inhibiting expression of profibrotic cytokines, and reducing MQ life-span by inhibiting steroid-induced CD300e expression.