Antilymphocyte globulins versus OKT3 as prophylactic treatment in highly sensitized renal transplant recipients.
Monoclonal antibodies were proposed as an effective prophylactic immunosuppressive treatment in highly sensitized patients (HSP). In this study we compared the results obtained in HSP treated with OKT3 or antilymphocyte globulins (ALG). From January 1989 to January 1993, 38 transplantations were performed in patients with high panel reactive antibodies (PRA > 50%). The group comprised 22 women and 16 men, mean age 45 +/- 2 (23-67) years; ten were second grafts and two were third grafts. Peak PRA was > or = 80% in 24 sensitized patients and 50-80% in 14 sensitized patients. Patients were randomly assigned to either prophylactic OKT3 (n = 15) or ALG (n = 23). Oral cyclosporin A (10 mg/kg) was started at day 8 in the OKT3 group and when the serum creatinine level decreased to 200 micromol/l in the ALG group. OKT3 was systematically withdrawn on day 10 but ALG was stopped only when total blood cyclosporin A concentration reached 150-200 ng/ml. In both groups, azathioprine (150 mg/day) and prednisolone were given. During the first months, 6/15 grafts were lost in the OKT3 group (three hyperacute rejections, one renal vein thrombosis, one steroid-resistant rejection, one death); in the ALG group 4/23 grafts were lost (one hyperacute rejection, two steroid-resistant rejections, one death). Side effects were significantly more frequent in the OKT3 group than in the ALG group. After 12 months of follow up, the graft survival was 71% (27/38) and did not significantly differ (log-rank test, NS) between the OKT3 (60%, 9/15) and the ALG group (78%, 18/23). We conclude that the use of the monoclonal antibody OKT3 as a prophylactic agent in HSP does not improve the early graft survival when compared with prophylactic ALG. Polyclonal antibodies, which react with many epitopes and are much better tolerated seem to offer a good strategy for induction therapy in this population.
Department of Nephrology, H pital Lapeyronie, Montpellier, France.
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Vela
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Cristol
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Chong
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Okamba
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Lorho
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Mion
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Mourad
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000627:therapeutic use*; D001379:Azathioprine / Q000627:therapeutic use; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000453:epidemiology; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000009:adverse effects / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000453:epidemiology; D011239:Prednisolone / Q000627:therapeutic use; D012086:Reoperation; D014777:Virus Diseases / Q000453:epidemiology
D000906:Antibodies; D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D016572:Cyclosporine; D011239:Prednisolone; D001379:Azathioprine