Sequential biological immunosuppression. Induction therapy with rabbit antithymocyte globulin

This paper describes 108 consecutively treated patients receiving 109 cadaveric (CD) and living donor (LD) renal allografts using a protocol of quadruple sequential immunosuppression with a rabbit anti-human thymocyte IgG (Thymoglobuline), azathioprine, tapering corticosteroids, and delayed introduction of cyclosporine A. The average length of induction was 6.1 d with an average Thymoglobuline dose of 2.0 mg/kg/d. The mean serum creatinine pre-transplant of the cohort was 877 +/- 263 (sd) mumol/L, 146 +/- 44 mumol/L by 3 months post-transplant, and 136 +/- 40 mumol/L at 1 yr. The overall 4-yr actuarial patient survival was 96.6%, and allograft survival was 88.6% at 2 yr and 83.6% at 4 yr. The incidence of acute rejection episodes defined by intention to treat was 32%. Additionally, eight patients in this series received retreatment with Thymoglobuline for a first acute rejection, and only one of these had a second rejection. This was in contrast to 5/11 recurrent rejections following steroid treatment only, and 5/13 recurrences following OKT3 treatment for the first rejection episode. The side-effect profile of Thymoglobuline was largely benign, and the biological agent was well tolerated with initial fever in 75%, chills in 27%, and leucopenia in 22% of the patients. All other drug-related adverse events had a prevalence of less than 3%, and clinical signs of meningismus were seen in only one patient. There were five associated episodes of CMV. We conclude that Thymoglobuline as part of a quadruple sequential immunosuppressive regimen for renal transplantation is well tolerated and can be associated with a good short- and long-term outcome of renal transplantation.