Prevention of acute rejection with antithymocyte globulin (Thymoglobuline): its potential to reduce corticosteroids.
We started using polyclonal antibody preparations (Thymoglobuline and Lymphoglobuline) as well as cyclosporine in 1981. A sequential immunosuppressive protocol was designed consisting of induction, delay cyclosporine introduction and corticosteroid withdrawal within the first 3 post-transplant months. This new immunosuppressive regimen has been applied to 1,671 patients: 1,439 received Thymoglobuline and 232 Lymphoglobuline; 1,083 were recipients of a primary renal transplant, 282 of a second transplant, 52 of third or fourth transplants, and 254 were recipients of a simultaneous kidney-pancreas transplant. The great majority of patients (96%) were recipients of cadaver organs; their age ranged from 3 to 77 years (average, 43+/-14). The overall incidence of acute rejection (intent-to-treat and biopsy-proven) was 23.7% (16% of patients had one episode and 8% had more than one episode), with 6.5% of rejections occurring after the third month and 3% after 12 months. The incidence of corticosteroid-resistant rejection was 8.7%. Between 1981 and 1990 (azathioprine maintenance) 40% of patients experienced an acute rejection while receiving a primary transplant versus 44% in case of retransplantation. Between 1991 and 1995 (CsA microemulsion maintenance), these percentages were reduced to 30 and 16%. After 1996 (mycophenolate mofetil and calcineurin inhibitors maintenance), the incidence of acute rejection was dramatically reduced to 8 and 6%, respectively in primary and retransplants. The incidence of patients free of corticosteroids was 61% at 3 months, 74% at 6 months, 79% at 1 year, 82% at 2 years, 89% at 5 years, 94% at 10 years and 100% at 20 years. A statistically better graft survival (up to 20 years, with similar patient survival) was observed in patients treated with Thymoglobuline as compared to Lymphoglobuline. Similar graft survival was observed in recipients of primary transplants as compared to retransplantation. The overall incidence of PTLD was 2.3%, with a significant decrease over the years achieving 0% after 1999. Thymoglobuline induction is a safe and highly efficient therapy to prevent rejection after kidney and kidney-pancreas transplantation. In association with CNI and antiproliferative immunosuppressive drugs, Thymoglobuline allowed the safe and early withdrawal of corticosteroids. This strategy of minimization of immunosuppression may have several beneficial effects in the long term.
Cantarovich
Diego
D
Department of Nephrology and Clinical Immunology, ITERT, Nantes University Hospital, Nantes, France. diego.cantarovich@chu-nantes.fr
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage; D005938:Glucocorticoids / Q000008:administration & dosage*; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage*; D012086:Reoperation
D000961:Antilymphocyte Serum; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone