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.
Guttmann
R D
RD
Centre for Clinical Immunobiology and Transplantation, McGill University, Montréal, Quebec, Canada.
Flemming
C
C
D000206:Actuarial Analysis; D000328:Adult; D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000627:therapeutic use*; D001379:Azathioprine / Q000008:administration & dosage / Q000627:therapeutic use; D002102:Cadaver; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D003586:Cytomegalovirus Infections / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology / Q000628:therapy; D006085:Graft Survival; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015994:Incidence; D016030:Kidney Transplantation / Q000276:immunology*; D007970:Leukopenia / Q000209:etiology; D019520:Living Donors; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008580:Meningism / Q000209:etiology; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D011817:Rabbits; D012008:Recurrence; D019233:Retreatment; D015996:Survival Rate
D000961:Antilymphocyte Serum; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D001379:Azathioprine; D008775:Methylprednisolone