Abstract: PUB025
Goreisan Attenuates AKI and Modulates AKI-to-CKD Transition After Ischemia-Reperfusion Injury
Session Information
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Eriguchi, Masahiro, Nara Kenritsu Ika Daigaku, Kashihara, Nara Prefecture, Japan
- Uemura, Takayuki, Nara Kenritsu Ika Daigaku, Kashihara, Nara Prefecture, Japan
- Matsui, Masaru, Nara Kenritsu Ika Daigaku, Kashihara, Nara Prefecture, Japan
- Tsuruya, Kazuhiko, Nara Kenritsu Ika Daigaku, Kashihara, Nara Prefecture, Japan
Background
Goreisan (GRS), a traditional Japanese Kampo medicine, is used for edema, diarrhea, and uremic symptoms. Recent studies suggest that GRS modulates the gut microbiota and attenuates inflammation and fibrosis; however, its protective effects in kidney ischemia–reperfusion injury (IRI) remain unclear. This study evaluated the effects of GRS in murine models of acute kidney injury (AKI) and AKI-to-CKD transition.
Methods
Two murine models were employed. In Study 1 (AKI model), mice underwent unilateral renal ischemia–reperfusion injury (IRI; 26 minutes) with simultaneous contralateral nephrectomy, creating a single-kidney model. Animals were assigned to Sham, IRI, and GRS groups (3.0% mixed diet), and samples were collected 2 days post-IRI.
In Study 2 (AKI-to-CKD model), mice underwent unilateral IRI with the contralateral kidney intact, followed by contralateral nephrectomy at 7 days to induce CKD. Mice were sacrificed 28 days after IRI. GRS was administered as continuous, post-IRI, or pre-IRI treatment. Kidney function (BUN), urinary KIM-1, and kidney cortical gene expression (MCP-1, Col1a1) were assessed.
Results
In Study 1, IRI significantly increased BUN compared with Sham in the control group (Sham vs IRI: −50.58, 95% CI −92.38 to −8.79, P=0.019), whereas this increase was markedly attenuated in the GRS group (difference −2.09, P=0.918), indicating attenuation of AKI. In contrast, inflammatory markers (IL-1β, LCN2, CCL2, ADGRE, TNFα) were not significantly different between groups.
In Study 2, BUN was significantly elevated in the IRI control group compared with Sham (P<0.0001). GRS treatment showed a tendency toward BUN reduction (difference 7.74, 95% CI −0.77 to 16.25, P=0.0728). Notably, improvement in BUN and urinary KIM-1 followed the order: continuous > post-IRI > pre-IRI treatment. Post-IRI treatment showed the smallest difference from control (difference 2.37, P=0.592), suggesting a potential therapeutic effect after AKI onset. Furthermore, kidney cortical expression of MCP-1 and Col1a1 was reduced in GRS-treated groups compared with IRI controls, indicating suppression of inflammation and fibrosis
Conclusion
GRS attenuated acute kidney dysfunction after IRI and showed a trend toward improved outcomes in AKI-to-CKD transition. Its effects may involve suppression of inflammation and fibrosis, particularly with post-injury administration.
Funding
- Commercial Support – Tsumura & Co., Ltd.