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Updated: Apr 21, 2026
A Rat Orthotopic Renal Transplantation Model for Renal Allograft Rejection
Published on: February 2, 2022
Increased Expression of p-Akt correlates with Chronic Allograft Nephropathy in a Rat Kidney Model
Li-Na Zhou1, Ning Wang2, Yang Dong3
1Department of Nephrology, The No. 2 Hospital of Xiamen, Xiamen, 361021, China.
Abstract:
Chronic allograft nephropathy (CAN) is the most common cause of chronic graft dysfunction leading to graft failure, our study investigates the expression and significance of p-Akt in the pathogenesis of CAN in rats. Kidneys of Fisher (F344) rats were orthotopically transplanted into Lewis (LEW) rats. The animals were evaluated at 4, 8, 12, 16, and 24 weeks post-transplantation for renal function and histopathology. Phosphorate Akt (p-Akt) protein expression was determined by Western blot and immunohistological assays. Our data show that 24-h urinary protein excretion in CAN rats increased significantly at week 16 as compared with F344/LEW controls. Allografts got severe interstitial infiltration of mononuclear cells at week 4 and week 8, but it was degraded as the time went on after week 16. Allografts markedly presented with severe interstitial fibrosis (IF) and tubular atrophy at 16 and 24 weeks. p-Akt expression was upregulated in rat kidneys with CAN, and the increase became more significant over time after transplantation. p-Akt expression correlated significantly with 24-h urinary protein excretion, serum creatinine levels, tubulointerstitial mononuclear cells infiltration, smooth muscle cells (SMCs) migration in vascular wall, and IF. It was concluded that p-Akt overexpression might be the key event that involved mononuclear cells infiltration and vascular SMCs migration at early stage, and IF and allograft nephroangiosclerosis at the late stage of CAN pathogenesis in rats.
Insights
Phosphorylated Akt (p-Akt) overexpression is implicated in chronic allograft nephropathy (CAN) pathogenesis in rats. Elevated p-Akt correlates with graft dysfunction, inflammation, and fibrosis, suggesting it as a key factor in CAN development.
Area of Science:
- Nephrology
- Immunology
- Molecular Biology
Background:
- Chronic allograft nephropathy (CAN) is the primary cause of kidney transplant failure.
- Understanding the molecular mechanisms driving CAN is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role and expression patterns of phosphorylated Akt (p-Akt) in the pathogenesis of CAN in a rat model.
- To determine the correlation between p-Akt levels and key indicators of CAN progression.
Main Methods:
- Orthotopic kidney transplantation performed in F344 into LEW rats.
- Assessment of renal function and histopathology at multiple time points post-transplantation.
- Quantification of p-Akt protein expression using Western blot and immunohistochemistry.
Main Results:
- CAN rats showed significantly increased urinary protein excretion and serum creatinine levels over time.
- Histopathology revealed progressive interstitial fibrosis, tubular atrophy, and mononuclear cell infiltration.
- p-Akt expression was upregulated in CAN kidneys, correlating significantly with proteinuria, interstitial fibrosis, and cellular infiltration.
Conclusions:
- p-Akt overexpression is a significant factor in the pathogenesis of CAN in rats.
- p-Akt may drive early-stage mononuclear cell infiltration and smooth muscle cell migration, and later-stage interstitial fibrosis and nephroangiosclerosis.
