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Effect of OKT3 in steroid-resistant renal transplant rejection
J J Petrie1, R J Rigby, C M Hawley
1Renal Transplant Unit, Princess Alexandra Hospital, Woolloongabba, Brisbane, Australia.
Abstract:
Between January 1, 1982, and November 1, 1986, 169 cadaver renal graft transplantations were performed at this hospital with CsA as induction therapy. OKT3 was not available in this period. Of these grafts, 15.9% were lost within 6 months, 10.7% from acute rejection (AR). Between November 1, 1986, and October 1, 1992, 483 cadaver renal graft transplantation were performed. Induction therapy included CsA and OKT3 was available. Of these grafts, 8.7% were lost inside 6 months, 3.1% from AR. Of these last 483 grafts, 113 received 125 courses of OKT3. Ten courses were prophylactic, and 115 courses in 103 patients were for rejection resistant to steroid therapy (biopsy proven in all but 2 cases. Ninety-three percent of rejection episodes treated with OKT3 responded, at least initially. Graft survival in OKT3-treated patients was 81%, 77%, and 76% at 6 months, 1 year, and 2 years, respectively. In contrast, graft survival in steroid-resistant rejection during the first period (without OKT3) was 59%, 57%, and 57% at these intervals. There were 8 infective deaths within 6 months in the 113 OKT3-treated patients, compared with 2 in the 343 who did not receive OKT3 (P < 0.001). There were 7 viral deaths in the OKT3 group compared with none in those not receiving OKT3 (P < 0.001). Prophylaxis with oral acyclovir and cotrimoxazole was instituted in October 1990 in OKT3-treated patients and ganciclovir use was increased. Since this change, no further viral deaths have occurred. OKT3 is a very effective antirejection agent, but its use is associated with an increased mortality from viral infections. With appropriate prophylaxis and treatment, however, this mortality can be reduced.
Insights
The introduction of OKT3 (muromonab-CD3) significantly reduced acute rejection and improved graft survival in renal transplant patients. However, its use increased the risk of fatal viral infections, which could be mitigated with prophylactic measures.
Area of Science:
- Nephrology
- Immunology
- Transplantation Medicine
Background:
- Cyclosporine (CsA) was the primary induction therapy for renal transplantation between 1982 and 1986.
- Acute rejection (AR) rates were high, with 10.7% of grafts lost within six months.
Purpose of the Study:
- To evaluate the impact of introducing OKT3 (muromonab-CD3) as induction therapy on renal graft survival and rejection rates.
- To assess the safety profile of OKT3, particularly concerning infectious complications.
Main Methods:
- Retrospective analysis of two cohorts of cadaver renal transplant recipients (1982-1986 without OKT3, 1986-1992 with OKT3).
- Comparison of graft loss, acute rejection rates, and patient mortality between groups.
- Analysis of OKT3 treatment courses for steroid-resistant rejection and associated outcomes.
Main Results:
- Graft loss within six months decreased from 15.9% to 8.7%, and AR from 10.7% to 3.1% after OKT3 introduction.
- OKT3 was effective in treating steroid-resistant rejection, with a 93% initial response rate and improved graft survival (81% at 6 months).
- OKT3 use was associated with increased mortality from infections (8 vs. 2 deaths) and viral infections (7 vs. 0 deaths), but this was reduced with prophylaxis.
Conclusions:
- OKT3 is a highly effective antirejection agent in renal transplantation, significantly improving graft survival.
- The benefits of OKT3 must be weighed against an increased risk of serious infections.
- Implementing prophylactic strategies, such as antiviral and antibacterial agents, can mitigate the infectious risks associated with OKT3 therapy.