Urinary Activin A is a novel biomarker reflecting renal inflammation and tubular damage in ANCA-associated vasculitis.

Abstract

Activin A, a member of the transforming growth factor-beta superfamily, is a critical modulator of inflammation and plays a key role in controlling the cytokine cascade that drives the inflammatory response. However, the role of activin A in inflammatory kidney diseases remains unknown. To address this issue, we examined here whether activin A can be detected in the kidney and/or urine from patients with antineutrophil cytoplasmic antibody (ANCA) -associated vasculitis (AAV). Fifty-one patients who had been diagnosed with AAV and were treated in our department between November 2011 to March 2018 were included in this study. Forty-one patients had renal complications (renal AAV). Serum and urinary activin A levels were measured by enzyme-linked immunosorbent assay. Correlation of urinary activin A concentration with clinical parameters was analyzed. Urinary activin A was undetectable in healthy volunteers. In contrast, urinary activin A concentration was significantly increased in patients with renal AAV but not in those with non-renal AAV. Urinary activin A concentration decreased rapidly after immunosuppressive treatment. There was a significant correlation of urinary activin A level with urinary protein, L-FABP, and NAG. Histologic evaluation revealed that urinary activin A levels were significantly higher in patients with cellular crescentic glomeruli than in those lacking this damage. In situ hybridization demonstrated that the mRNA encoding the activin A βA subunit was undetectable in normal kidneys but accumulated in the proximal tubules and crescentic glomeruli of the kidneys of patients with renal AAV. Immunostaining showed that activin A protein also was present in the proximal tubules, crescentic glomeruli, and macrophages infiltrating into the interstitium in the kidneys of patients with renal AAV. These data suggested that urinary activin A concentration reflects renal inflammation and tubular damage in AAV and may be a useful biomarker for monitoring renal AAV.

• Authors: Yoshinori Takei, Shunsuke Takahashi, Masao Nakasatomi, Toru Sakairi, Hidekazu Ikeuchi, Yoriaki Kaneko, Keiju Hiromura, Yoshihisa Nojima, Akito Maeshima
• Journal: PloS one (PLoS One) Vol. 14 Issue 10 Pg. e0223703 ( 2019) ISSN: 1932-6203 [Electronic] United States
• PMID: 31613925 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• RNA, Messenger
• activin A
• inhibin beta A subunit
• Activins
• Inhibin-beta Subunits

Topics

• Activins (genetics, metabolism, urine)
• Aged
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis (complications, genetics, urine)
• Biomarkers (urine)
• Biopsy
• Female
• Humans
• Inflammation (complications, urine)
• Inhibin-beta Subunits (genetics, metabolism)
• Kidney Tubules (metabolism, pathology)
• Male
• RNA, Messenger (genetics, metabolism)