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OKT3 treatment of steroid-resistant renal allograft rejection
Abstract:
The monoclonal antibody, Orthoclone OKT3 (OKT3), has been used with great efficacy in a prospective multicenter trial as therapy for first rejection episodes in cadaveric donor (CD) renal allograft recipients treated with azathioprine (AZA) and prednisone (P). However, although almost all rejection episodes were reversed, recurrent rejection occurred in approximately two-thirds of OKT3-treated patients in this earlier trial; infections also occurred in about two-thirds of patients, often related to the additional immunosuppression necessary to reverse the rerejection episodes. In the current series of patients, OKT3 was used to treat rejection in CD renal graft recipients in a protocol differing from the multicenter trial in two respects: baseline immunosuppression was cyclosporine (CsA) and P or CsA, AZA, and P (probably more potent immunosuppressive combinations than the AZA and P in the multicenter trial); and OKT3 treatment was reserved for rejection episodes resistant to 3 bolus infusions of methylprednisolone (MP), 5-10 mg/kg, rather than as primary therapy for first rejection episodes. Using this protocol, 46 of 74 rejection episodes (62%) diagnosed between 3/85 and 3/86 in CD renal allograft recipients were treated successfully with MP. Of the remaining 28 steroid-resistant rejection episodes, 27 (96%) were reversed with a 7-14-day course of OKT3, 5 mg/day. Only 5 recurrent rejection episodes (19%) have been observed in the 2-14-month follow-up period after OKT3 treatment; infections have occurred in 10 patients (36%), and three grafts (11%) have been lost in OKT3 treated patients. These results suggest that recurrent rejection and subsequent infection after OKT3 is used to treat rejection may be reduced in a protocol where CD renal allograft recipients are treated with baseline immunosuppression regimens including CsA and where OKT3 is reserved for steroid-resistant rejection. This approach appears to be both more cost-effective than, and as effective therapeutically as, treating all first rejection episodes with the monoclonal antibody.
Insights
Orthoclone OKT3 (OKT3) effectively treats renal allograft rejection. Using OKT3 for steroid-resistant rejection with cyclosporine baseline immunosuppression reduces recurrent rejection and infections compared to treating all first rejections.
Area of Science:
- Nephrology
- Immunology
- Transplantation
Background:
- Orthoclone OKT3 (OKT3) effectively reverses renal allograft rejection episodes.
- Previous trials showed high rates of recurrent rejection and infection with OKT3 primary therapy.
- Alternative protocols are needed to optimize OKT3 use in cadaveric donor (CD) renal allograft recipients.
Purpose of the Study:
- To evaluate the efficacy of OKT3 for steroid-resistant rejection in CD renal allograft recipients.
- To assess the impact of baseline immunosuppression with cyclosporine (CsA) on OKT3 treatment outcomes.
- To compare recurrent rejection and infection rates between different OKT3 treatment strategies.
Main Methods:
- A protocol using CsA-based immunosuppression was implemented for CD renal allograft recipients.
- OKT3 treatment was reserved for rejection episodes resistant to methylprednisolone (MP) bolus infusions.
- Patient outcomes, including rejection reversal, recurrence, and infection rates, were monitored.
Main Results:
- 62% of rejection episodes were successfully treated with MP.
- 96% of steroid-resistant rejection episodes were reversed with OKT3.
- Recurrent rejection (19%) and infections (36%) were reduced compared to previous OKT3 protocols.
Conclusions:
- Reserving OKT3 for steroid-resistant rejection in CsA-treated CD renal allograft recipients reduces complications.
- This approach offers a cost-effective and therapeutically effective alternative to using OKT3 for all first rejection episodes.
- Optimized OKT3 use improves outcomes in renal transplantation.