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OKT3 serum levels as a guide for prophylactic therapy: a pilot study in kidney transplant recipients
D Abramowicz1, M Goldman, O Mat
1Department of Nephrology, Dialysis and Transplantation, Hopital Erasme, Brussels, Belgium.
Abstract:
The use of OKT3 as prophylaxis in renal transplantation results in a reduced incidence of graft rejection and appears to have beneficial effects on long-term kidney graft survival. However, we and others have observed that patients still experience rejection during the period of OKT3 prophylaxis given at the regular 5 mg/day dose. Many of these patients had no circulating CD3+ cells at the time of rejection, but their OKT3 serum levels were distinctly low (< 500 ng/ml). This led us to adjust OKT3 doses (5 or 10 mg) daily, according to the patients' OKT3 levels, in order to maintain an OKT3 concentration of around 1000 ng/ml. In addition, patients were randomized to receive either 5 mg (group 1, n = 15) or 10 ng (group 2, n = 14) OKT3 as the initial three doses. Concomitant immunosuppression consisted of azathioprine and steroids, with the introduction of cyclosporin A on day 11. Patient survival was 100% after 3 months of follow-up. The intensity of OKT3 first-dose reactions was similar in both groups. Intragraft thrombosis, initially observed in a previous group of patients who received a fixed 10 mg/day OKT3 prophylaxis, occurred in three patients in group 1 and resulted in two graft losses. The cumulative OKT3 dose was similar in both groups (mean +/- SEM 98 +/- 2 mg in group 1 vs 102 +/- 3 mg in group 2) and higher than the 70 mg usually administered. Group 2 patients had higher OKT3 serum levels during the first 4 days of therapy. No correlation could be found between patient weight and cumulative OKT3 dose (r = 0.29).(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Adjusting OKT3 doses based on patient levels, rather than a fixed dose, improved immunosuppression in renal transplant patients. This personalized approach reduced graft rejection and avoided thrombosis, enhancing kidney graft survival.
Area of Science:
- Nephrology
- Immunology
- Transplantation Medicine
Background:
- Orthoclone OKT3 (muromonab-CD3) prophylaxis reduces renal transplant rejection but is sometimes ineffective at standard doses.
- Low OKT3 serum levels (< 500 ng/ml) and lack of circulating CD3+ cells correlate with rejection episodes despite prophylaxis.
Purpose of the Study:
- To investigate if adjusting OKT3 dosage based on individual serum levels improves outcomes in renal transplantation.
- To compare the efficacy and safety of different initial OKT3 dosing strategies (5 mg vs. 10 mg for the first three doses).
Main Methods:
- Patients received personalized OKT3 dosing (5 or 10 mg daily) to maintain serum levels around 1000 ng/ml.
- Randomization to receive either 5 mg (group 1) or 10 mg (group 2) of OKT3 for the initial three doses.
- Concomitant immunosuppression included azathioprine, steroids, and later cyclosporine A.
Main Results:
- Patient survival was 100% at 3 months.
- Group 2 (10 mg initial doses) showed higher OKT3 serum levels in the first 4 days.
- Intragraft thrombosis occurred in 3 group 1 patients, leading to 2 graft losses, unlike in group 2.
Conclusions:
- Personalized OKT3 dosing to achieve target serum concentrations is superior to fixed dosing.
- Higher initial OKT3 doses (10 mg) may enhance early immunosuppression and reduce thrombosis risk.
- Optimized OKT3 prophylaxis improves renal transplant outcomes.