Kidney Week

Abstract: TH-PO0808

Goreisan Attenuates Cardiac Remodeling in CKD with Pressure Overload-Induced Cardiac Hypertrophy via Suppression of Aquaporin-1 Signaling

Session Information

• CKM Axis: Vascular Dysfunction, Atherosclerosis, and Heart Failure in Kidney Diseases
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Cardiovascular-Kidney-Metabolic Health

• 601 Cardiovascular-Kidney-Metabolic Health: Basic

Authors

• Hirai, Toshiyuki, Division of Nephrology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan

Toshiyuki Hirai, MD

• Goto, Shunsuke, Division of Nephrology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan

Shunsuke Goto, MD, PhD

• Okamoto, Hayaki, Division of Nephrology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan

Hayaki Okamoto, MD

• Tabuchi, Momoko, Division of Nephrology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan

Momoko Tabuchi, MD

• Fujii, Hideki, Division of Nephrology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan

Hideki Fujii, MD, PhD, FASN

Background

Chronic kidney disease (CKD) is associated with cardiac remodeling characterized by left ventricular hypertrophy (LVH) and fibrosis, which contribute to adverse cardiovascular outcomes. Goreisan (GRS), a traditional Kampo medicine, has been reported to improve fluid homeostasis and may reduce heart failure events; however, its effects on CKD-associated cardiac remodeling remain unclear. This study aimed to investigate the effects of GRS on cardiac remodeling in CKD, with and without pressure overload-induced cardiac hypertrophy, focusing on aquaporin-1 (AQP1) and oxidative stress–related pathways.

Methods

Male Sprague–Dawley rats were used. LVH was induced by pressure overload using transverse aortic constriction at 6 weeks of age, and CKD was induced by 5/6 nephrectomy at 7 and 8 weeks. Rats were assigned to sham, CKD, and CKD with LVH (CKD/LVH) groups. The CKD and CKD/LVH groups were further divided into vehicle- and GRS-treated (1.0 g/kg) groups and treated for 4 weeks. At 14 weeks, echocardiography was performed, after which animals were sacrificed for analysis of blood and urine parameters, mRNA and protein expression, and cardiac histopathology.

Results

AQP1 expression was upregulated at both mRNA and protein levels in the CKD/LVH group compared with the sham group. Myocardial fibrosis area and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were significantly increased in the CKD group compared with the sham group. These changes were further exacerbated in the CKD/LVH group, which also showed cardiomyocyte hypertrophy, an increased β-myosin heavy chain (MHC)/α-MHC ratio, elevated connective tissue growth factor (CTGF) expression, and higher urinary 8-OHdG levels. Phosphorylation of ERK and p38 was increased exclusively in the CKD/LVH group. GRS reduced AQP1 expression and attenuated cardiomyocyte hypertrophy, myocardial fibrosis, the β-MHC/α-MHC ratio, CTGF expression, and urinary 8-OHdG levels in the CKD/LVH group. GRS also suppressed phosphorylation of ERK and p38.

Conclusion

GRS attenuated cardiac remodeling induced by CKD and pressure overload, possibly by suppressing AQP1 and downstream mitogen-activated protein kinase signaling, thereby reducing oxidative stress, hypertrophy, and fibrosis. These findings suggest that GRS may represent a potential therapeutic strategy for cardiac remodeling in CKD.

Funding

• Commercial Support – Tsumura & Co.