Kidney Week

Abstract: SA-PO0251

Urinary Activin A as a Potential Biomarker of AKI-to-CKD Transition After Ischemia-Reperfusion Injury

Session Information

• AKI: Mechanisms - Cell Signaling
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Takahashi, Shunsuke, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Shunsuke Takahashi, MD, PhD

• Okada, Mari, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Mari Okada, MD

• Abe, Erika, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Erika Abe, MD

• Sekiguchi, Momoko, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Momoko Sekiguchi, MD

• Hamada, Takayuki, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Takayuki Hamada, MD

• Maeshima, Akito, Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, Kawagoe, Saitama, Japan

Akito Maeshima, MD, PhD

Background

Activin A, a member of the transforming growth factor-β superfamily, regulates cell growth and differentiation in various tissues. We previously demonstrated that activin A is not expressed in normal kidneys but is induced in ischemic kidneys, where it negatively regulates renal repair after injury and acts as a potent activator of renal interstitial fibroblasts. We have also shown that urinary activin A reflects the severity of acute kidney injury (AKI) in both experimental models and patients. Based on these findings, the present study aimed to investigate the potential role of activin A in the transition from AKI to chronic kidney disease (CKD).

Methods

Male Wistar rats were subjected to 45 min of bilateral renal ischemia-reperfusion injury. Animals were sacrificed on days 2, 7, 14, 28, and 56 after surgery. Kidney tissues and urine samples were collected for biochemical, histological, and immunohistochemical analyses. Urinary activin A levels were measured by enzyme-linked immunosorbent assay. Renal fibrosis was evaluated histologically.

Results

Serum creatinine and blood urea nitrogen levels were markedly elevated on day 2 after ischemia-reperfusion injury but had nearly returned to baseline by day 7. In contrast, renal interstitial fibrosis became evident on day 14 and progressively worsened on days 28 and 56, indicating the development of chronic renal damage after apparent functional recovery. Immunoreactive activin A was detected in proximal tubular epithelial cells in the outer medulla of ischemic kidneys, whereas it was absent in normal kidneys. Urinary activin A was undetectable in normal rats but became detectable after ischemia-reperfusion injury. Time-course analysis revealed heterogeneous urinary activin A excretion patterns among individual animals, with single or biphasic peaks observed on days 2, 7, or 14. Notably, animals with minimal renal fibrosis did not show a sustained increase in urinary activin A during the observation period.

Conclusion

This renal ischemia-reperfusion model recapitulates key features of AKI-to-CKD transition, characterized by progressive interstitial fibrosis despite early recovery of renal function. Activin A may be involved in maladaptive repair processes that promote AKI-to-CKD progression. Urinary activin A may serve as a potential biomarker for identifying ongoing tissue injury and disease transition after AKI.