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Updated: Aug 20, 2026
A Rat Orthotopic Renal Transplantation Model for Renal Allograft Rejection
Published on: February 2, 2022
Effects of progesterone and selective oestrogen receptor modulators on chronic allograft nephropathy in rats
Balazs Antus1, Shanying Liu, Yousheng Yao
1Department of Nephrology,, Klinikum rechts der Isar, Munich, Germany. antbal@net.sote.hu
Background:
We recently demonstrated that oestrogens ameliorate the progression of chronic allograft nephropathy (CAN). In our present study, we investigated the role of progesterone and selective oestrogen receptor modulators (SERMs) in this process.
Methods:
Female Fisher (F344) kidneys were orthotopically transplanted into intact or ovariectomized female Lewis recipients. Ovariectomized recipients were divided into four groups and were treated with either progesterone alone or in combination with oestradiol, oestradiol alone or vehicle. Intact recipients were divided into three groups and were treated with SERMs such as tamoxifen and one of its new derivatives, droloxifene or vehicle. Animals were harvested 24 weeks after transplantation for histological and immunohistological studies as well as for molecular analysis.
Results:
Administration of progesterone resulted in increased urinary protein excretion as well as profound glomerulosclerosis and mononuclear cell infiltration. The combined treatment had similar detrimental effects on the development of CAN. In contrast, oestradiol treatment alone improved graft function, reduced glomerulosclerosis and diminished cellular infiltration. SERMs again impaired allograft function and promoted the development of CAN. Renal allograft damage paralleled intragraft mRNA expression of transforming growth factor-beta1 in all groups.
Conclusions:
Our results suggest that addition of progesterone diminishes the beneficial effects of oestrogens on the development of CAN in rats. Similarly to progesterone, SERMs worsened long-term renal allograft outcome.
Insights
Progesterone and selective oestrogen receptor modulators (SERMs) worsen chronic allograft nephropathy (CAN) outcomes in rats. Oestradiol alone, however, ameliorates CAN progression, highlighting differential hormonal effects on kidney transplant health.
Area of Science:
- Nephrology
- Immunology
- Endocrinology
Background:
- Oestrogens have shown beneficial effects in mitigating chronic allograft nephropathy (CAN).
- The roles of progesterone and selective oestrogen receptor modulators (SERMs) in CAN progression remain less understood.
Purpose of the Study:
- To investigate the impact of progesterone and SERMs on the development of CAN.
- To compare the effects of progesterone, SERMs, and oestradiol on renal allograft outcomes.
Main Methods:
- Kidney transplantation was performed in female Lewis rats, with recipients treated with progesterone, oestradiol, SERMs (tamoxifen, droloxifene), or vehicle.
- Histological, immunohistological, and molecular analyses were conducted 24 weeks post-transplantation.
- Assessment included urinary protein excretion, glomerulosclerosis, cellular infiltration, and intragraft mRNA expression of transforming growth factor-beta1.
Main Results:
- Progesterone administration exacerbated CAN, increasing proteinuria, glomerulosclerosis, and inflammation.
- Oestradiol treatment alone improved graft function, reduced glomerulosclerosis, and diminished cellular infiltration.
- SERMs impaired allograft function and promoted CAN development, with renal damage correlating with transforming growth factor-beta1 expression.
Conclusions:
- Progesterone diminishes the protective effects of oestrogens on chronic allograft nephropathy in a rat model.
- Selective oestrogen receptor modulators negatively impact long-term renal allograft outcomes, similar to progesterone.
- These findings underscore the complex hormonal regulation of kidney transplant rejection and suggest caution in using certain hormone-based therapies.
