Related Experiment Video
Updated: Jul 18, 2026
Murine Full-thickness Skin Transplantation
Published on: January 2, 2017
FTY720 in combination with cyclosporine--an analysis of skin allograft survival and renal function
Francieli Ruiz Silva1, Lea Bueno Lucas Silva, Patricia Maluf Cury
1UNESP, Ibilce, São Jose do Rio Preto, SP, Brazil.
Abstract:
Acute and chronic nephrotoxicity caused by CsA continuous administration impair kidney allograft survival. Several clinical and experimental protocols have shown benefits to the kidney after decreasing CsA dose, withdrawing the drug or delaying its introduction after transplantation. FTY720 is a new compound that has immunosuppressive characteristics and increase allograft survival in animal models without causing the side effects of calcineurin inhibitors (CNIs). FTY720 described mechanism of action that consists to alter the lymphocyte migration pattern without impairment of the immune system response against pathogens. In our mice model, FTY720 administered alone or in combination with CsA during 21 days increased skin allograft survival in a fully mismatched strain combination and did not cause significant changes in renal function. Moreover, renal structure was normal in all groups suggesting that at low doses (10 mg/kg/day) CsA can be associated during short-term period to other immunosuppressive drugs, i.e. FTY720 without affecting the kidney. Combination of immunosuppressive compounds with FTY720 and/or delayed introduction of low cyclosporine dose could prevent graft rejection and avoid nephrotoxicity.
Insights
New research shows FTY720, an immunosuppressant, can be combined with low-dose cyclosporine (CsA) to improve skin allograft survival without causing kidney damage. This combination may prevent rejection and reduce nephrotoxicity in transplantation.
Area of Science:
- Immunology
- Nephrology
- Transplantation Medicine
Background:
- Cyclosporine (CsA) is a calcineurin inhibitor (CNI) crucial for immunosuppression post-transplantation.
- Continuous CsA administration can lead to acute and chronic nephrotoxicity, impairing kidney allograft survival.
- Strategies to mitigate CsA nephrotoxicity include dose reduction, withdrawal, or delayed introduction.
Purpose of the Study:
- To evaluate the efficacy and renal safety of FTY720, a novel immunosuppressant, alone and in combination with CsA.
- To determine if FTY720 can enhance allograft survival without the nephrotoxic side effects associated with CNIs.
- To assess the impact of short-term, low-dose CsA combined with FTY720 on renal function and structure.
Main Methods:
- A mouse model was used to assess skin allograft survival.
- Mice received FTY720 alone or in combination with CsA (10 mg/kg/day) for 21 days.
- Renal function and kidney structure were evaluated in all treatment groups.
Main Results:
- FTY720 alone and in combination with CsA significantly increased skin allograft survival in a fully mismatched strain combination.
- No significant changes in renal function were observed in any treatment group.
- Histopathological examination revealed normal renal structure across all groups, indicating no CsA-induced nephrotoxicity at the tested dose and duration.
Conclusions:
- FTY720 demonstrates immunosuppressive properties that enhance allograft survival.
- Short-term co-administration of low-dose CsA with FTY720 is safe for the kidney and does not induce nephrotoxicity.
- Combining FTY720 with CsA or employing delayed introduction of low-dose CsA presents a promising strategy to prevent graft rejection while avoiding nephrotoxicity.
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