Abstract: TH-PO244

Identification of Urinary Activin A as a Novel Biomarker for AKI

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic


  • Takahashi, Shunsuke, Gunma University Graduate School of Medicine, Maebashi, Japan
  • Takei, Yoshinori, Gunma University School of Medicine, Maebashi, GUNMA, 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

Activin A, a member of TGF-beta superfamily, is known to regulate cell growth and differentiation in various tissues. We previously reported that activin A, which was absent in normal kidney, was increased in the ischemic rat kidney and negatively regulates the repair process of the kidney after injury (Maeshima et al. J Am Soc Nephrol 2001). To further investigate the role of activin A in acute kidney injury (AKI), we examined whether activin A can be detected in the urine of mice and humans with AKI.


Ischemia-reperfusion injury (I/R) was induced in C57BL/6 mice. At the indicated periods after operation, the kidneys and urine were collected for analysis. Expression and localization of activin A in ischemic kidneys (real-time PCR, immunostaining, and in situ hybridization) and urinary activin A (ELISA) were examined. Urine samples were also collected from fifteen patients with AKI as well as from eight healthy volunteers. Correlations of urinary activin A with other parameters were analyzed.


Expression of activin A was markedly increased in the ischemic mouse kidney and peaked at 24 hours after I/R. Immunoreactive activin A was detected in proximal tubular cells of the outer medulla in ischemic kidneys, but not in normal kidneys. Activin A was absent in the urine of normal mice. In contrast, activin A was detectable in the urine of ischemic mice and bimodal peak (3 hours and 48 hours after I/R) was observed. In situ hybridization demonstrated that activin mRNA was expressed in tubular cells of the ischemic kidney, but was not in normal kidneys. Urinary activin A level became higher according to the ischemic periods. Urinary activin A was almost undetectable in healthy volunteers, but was significantly increased in patients with renal-AKI (7.2 ± 2.6 vs. 48.6 ± 15.3 pg/ml, p<0.05). Interestingly, urinary activin A was absent in the urine from patients with pre-renal AKI due to dehydration. There was a significant correlation of urinary activin A level with urinary follistatin (activin antagonist), but not with urinary KIM-1, urinary protein and serum creatinine.


Urinary activin A can be detected in mice and humans with AKI and might be a useful biomarker reflecting the severity of AKI.


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