Abstract: TH-PO0389
The Spontaneously Hypercholesterolemic (SHC) Rat as a Translational Model of FSGS: Renoprotective Effects of Irbesartan
Session Information
- Glomerular Diseases: Genetics to Therapeutics
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Takagahara, Shuichi, Axcelead Drug Discovery Partners Kabushiki Kaisha, Fujisawa, Kanagawa Prefecture, Japan
- Kobayashi, Ryosuke, Axcelead Drug Discovery Partners Kabushiki Kaisha, Fujisawa, Kanagawa Prefecture, Japan
- Nio, Yasunori, Axcelead Drug Discovery Partners Kabushiki Kaisha, Fujisawa, Kanagawa Prefecture, Japan
- Kaneko, Manami, Axcelead Drug Discovery Partners Kabushiki Kaisha, Fujisawa, Kanagawa Prefecture, Japan
Background
Focal segmental glomerulosclerosis (FSGS) is a major cause of progressive kidney disease. However, many commonly used animal models are driven by toxic, surgical, or monogenic mechanisms, limiting their relevance to the heterogeneous and multifactorial pathophysiology of human FSGS. SHC (spontaneously hypercholesterolemic) rats develop proteinuria, renal dysfunction, and glomerulosclerosis associated with genetically driven hyperlipidemia and hypertension, recapitulating features of secondary FSGS. In this study, we assessed the effects of irbesartan on renal function and pathology in SHC rats.
Methods
Male SHC rats (aged 10 weeks) received irbesartan (50 mg/kg/day, oral administration) for 14 weeks. Urine albumin-to-creatinine ratio (uACR), blood urea nitrogen (BUN), and total cholesterol levels were measured at 3, 6, and 12 weeks after treatment initiation. Renal function was assessed by measurement of glomerular filtration rate (GFR) at 23 weeks of age. At the end of the study, kidney tissues were subjected to histological and gene expression analyses.
Results
SHC rats exhibited marked increases in uACR, a decline in GFR, and focal glomerulosclerotic lesions, consistent with the pathological features of FSGS patients. Treatment with irbesartan attenuated elevations in uACR, plasma cholesterol, BUN and TBARS levels, accompanied by increased expression of SOD1 and SOD2 mRNA, while preventing the decline in GFR. Histopathological analyses demonstrated attenuation of glomerular lesions with a tendency toward a reduced number of affected glomeruli in irbesartan-treated rats.
Conclusion
These results suggest that the ameliorative effects of irbesartan in SHC rats may be mediated through normalization of blood pressure, lipid levels, and reduced oxidative stress. These findings indicate that irbesartan exerts renoprotective effects in SHC rats consistent with its clinical efficacy, supporting the utility of SHC rats as a translational model for evaluating therapeutic interventions targeting FSGS.
(A) Histopathological images (focal sclerotic lesion, arrowhead) and (B) protein albumin changes in SHC rats