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[Nephrotoxicity of anti-CD3 monoclonal antibodies]
M L Alegre1, M Depierreux, S Florquin
1Département médico-chirurgical de Néphrologie, Hôpital Erasme.
Abstract:
The OKT3 monoclonal antibody entails a transient acute nephrotoxicity when used either to prevent or to treat renal allograft rejection. This nephrotoxicity was reproduced experimentally in mice injected with 145-2C11, an anti-CD3 monoclonal antibody which shares many properties with OKT3. Both clinical and experimental data suggest that the renal lesions are due to the systemic release of cytokines that occurs prior to the immunosuppression. Pre-treatment with corticosteroids before the injection of anti-CD3 monoclonal antibody mitigates both the release of cytokines and the nephrotoxicity, in a dose-dependent manner. Experimental data suggest that very high doses of methylprednisolone (50 mg/kg) administered 2 to 3 hours before the monoclonal antibody are necessary to obtain an optimal protection.
Insights
Monoclonal antibody OKT3 causes acute kidney injury during renal transplant rejection treatment. Pre-treating with corticosteroids, especially methylprednisolone, significantly reduces this nephrotoxicity by mitigating cytokine release.
Area of Science:
- Nephrology
- Immunology
- Transplantation
Background:
- The monoclonal antibody OKT3 is used to prevent or treat renal allograft rejection.
- OKT3 administration can cause transient acute nephrotoxicity.
- This nephrotoxicity is linked to cytokine release preceding immunosuppression.
Purpose of the Study:
- To investigate the mechanism of OKT3-induced nephrotoxicity.
- To evaluate the efficacy of corticosteroid pre-treatment in mitigating anti-CD3 antibody-related nephrotoxicity.
Main Methods:
- Reproduced OKT3-like nephrotoxicity in mice using the 145-2C11 anti-CD3 antibody.
- Administered varying doses of methylprednisolone prior to anti-CD3 antibody injection.
- Monitored cytokine release and renal lesions.
Main Results:
- Anti-CD3 antibody administration induced nephrotoxicity and systemic cytokine release in mice.
- Corticosteroid pre-treatment dose-dependently reduced both cytokine release and nephrotoxicity.
- Optimal protection was achieved with high-dose methylprednisolone (50 mg/kg) given 2-3 hours before the antibody.
Conclusions:
- The nephrotoxicity associated with anti-CD3 monoclonal antibodies is mediated by cytokine release.
- Corticosteroid pre-treatment is an effective strategy to prevent this adverse effect.
- Specific dosing and timing of methylprednisolone are crucial for optimal nephroprotection.