Abstract: PO0240
Urinary Follistatin: A Novel Biomarker for Monitoring the Severity of AKI
Session Information
- AKI: Clinical, Outcomes, and Trials
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 102 AKI: Clinical, Outcomes, and Trials
Authors
- Nagayama, Izumi, Saitama Ika Daigaku Sogo Iryo Center, Kawagoe, Saitama, Japan
- Nagata, Daisuke, Jichi Ika Daigaku, Shimotsuke, Tochigi, Japan
- Hasegawa, Hajime, Saitama Ika Daigaku Sogo Iryo Center, Kawagoe, Saitama, Japan
- Maeshima, Akito, Saitama Ika Daigaku Sogo Iryo Center, Kawagoe, Saitama, Japan
Group or Team Name
- Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe, Saitama 350-8550, Japan
Background
Activin A, a member of the TGF-beta superfamily, which was absent in normal kidney, was increased in the ischemic rat kidney and negatively regulates the repair process of the kidney after injury. However, the role of follistatin, an endogenous antagonist of activins, in the kidney is unknown. To address this issue, we examined the localization of follistatin in normal and ischemic rat kidney, and measured urinary follistatin in both rats and human with AKI.
Methods
Using vascular clamps, renal ischemia was induced for 45 min in 8-week-old male Wistar rats. Localization of follistatin in the kidney and urinary follistatin was examined by immunostaining and ELISA, respectively. Renal tissues of Nephrectomized kidney was used as normal human kidney (Approved number A18-150). Patients with AKI (n=98) and healthy adults (n=10) were enrolled in this study (Approved number A18-081 and A18-089). Serum and urinary follistatin was measured by ELISA. Correlations of urinary follistatin with other clinical parameters were analyzed.
Results
Follistatin was localized in renal tubules of normal rat kidney. Follistatin-expressing cells were positive for NCC and uromodulin, but were negative for AQP1 or AQP2. In contrast, follistatin expression was increased in the inner medulla of the kidney after renal ischemia. Urinary follistatin, undetectable in normal rats, was significantly increased with a peak at 24 h after renal ischemia. Consistent with normal rat kidney, follistatin was localized in renal tubules of normal human kidney. Urinary follistatin, undetectable in healthy adults, was significantly increased in patients with AKI (0.0 ± 0.0 vs. 433.6 ± 190.0 pg/mL, p< 0.05) and was positively correlated with the severity of AKI. Urinary follistatin was significantly increased in patients requiring renal replacement therapy compared to those who did not (911.7 ± 428.3 vs. 94.4 ± 40.0 pg/mL, p< 0.05). There was a significant correlation of urinary follistatin with urinary protein, alpha1-microglobulin, NGAL, but not with serum follistatin.
Conclusion
Follistatin, which is localized in the distal tubules of normal kidney, become detectable in the urine of AKI patients. Urinary follistatin may reflect the severity of acute tubular damage.