Abstract: TH-PO394

Urinary Activin A Is a Novel Biomarker Reflecting Renal Inflammation and Tubular Damage in ANCA-Associated Vasculitis

Session Information

Category: Cell Biology

  • 203 Growth Factors, Chemokines, Autacoids

Authors

  • Takei, Yoshinori, Gunma University School of Medicine, Maebashi, Gunma, Japan
  • Takahashi, Shunsuke, Gunma University Graduate School of Medicine, Maebashi, Japan
  • Nakasatomi, Masao, Gunma University, Maebashi, GUNMA, Japan
  • Sakairi, Toru, Gunma University Graduate School of Medicine, Japan, Maebashi, GUNMA, Japan
  • Ikeuchi, Hidekazu, Gunma university graduate school of medicine, Maebashi, GUNMA, Japan
  • Kaneko, Yoriaki, Gunma University Graduate School of Medicine, Maebashi, Japan
  • Hiromura, Keiju, Gunma University Graduate School of Medicine, Maebashi, Japan
  • Nojima, Yoshihisa, Gunma University, Maebashi, GUNMA, Japan
  • Maeshima, Akito, Gunma University Graduate School of Medicine, Maebashi, Japan
Background

Activin A, a member of TGF-beta superfamily, is known to regulate cell growth and differentiation in various tissues. It has been reported that activin A is involved in kidney development, tubular regeneration, and renal fibrosis in rodents. However, the role of activin A in kidney diseases remains unknown in human. To address this issue, we analyzed renal biopsy specimens and urine from patients with ANCA-associated vasculitis (AAV).

Methods

Thirty-seven patients with biopsy-proven AAV who were treated in our department from 2011 and 2015 were included in this study. Serum activin A, urinary activin A, urinary follistatin (an activin antagonist), and urinary KIM-1 were measured by ELISA. Urine from healthy volunteers and rheumatic disease patients with normal urinalysis (control patients) were also used. The localization of activin A in renal biopsy specimens from AAV patients was examined by immunostaining. Normal kidney specimens from patients who underwent nephrectomy were used as a control.

Results

Urinary activin A was almost undetectable in healthy volunteers, but was significantly increased in AAV patients (7.2 ± 2.6 vs. 122.0 ± 38.6 ng/gCr, p<0.001). Urinary activin A levels of these patients was rapidly decreased after treatment. There was a significant correlation of urinary activin A level with urinary KIM-1 and urinary protein. On the other hand, compared with control patients, urinary follistatin levels were decreased in AAV patients (673.1 ± 135.3 vs. 291.7 ± 38.8 ng/gCr, p<0.05). Activin A was localized in the cytoplasm of distal tubules of normal kidneys. In contrast, activin A was present not only in distal tubules, but also in the apical lumen of proximal tubules, and infiltration macrophages in patients with AAV.

Conclusion

These data suggest that urinary activin A reflects renal inflammation and tubular damage in ANCA-associated vasculitis.

Funding

  • Commercial Support