Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation.

BACKGROUND: Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation. METHODS: A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.5 mg/kg/ day) or Atgam (15 mg/kg/day). The primary end point was rejection reversal (return of serum creatinine level to or below the day 0 baseline value). RESULTS: A total of 163 patients were enrolled at 25 transplant centers in the United States. No differences in demographics or transplant characteristics were noted. Intent-to-treat analysis demonstrated that Thymoglobulin had a higher rejection reversal rate than Atgam (88% versus 76%, P=0.027, primary end point). Day 30 graft survival rates (Thymoglobulin 94% and Atgam 90%, P=0.17), day 30 serum creatinine levels as a percentage of baseline (Thymoglobulin 72% and Atgam 80%; P=0.43), and improvement in posttreatment biopsy results (Thymoglobulin 65% and Atgam 50%; P=0.15) were not statistically different. T-cell depletion was maintained more effectively with Thymoglobulin than Atgam both at the end of therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 90 days after therapy, occurred less frequently with Thymoglobulin (17%) versus Atgam (36%) (P=0.011). A similar incidence of adverse events, post-therapy infections, and 1-year patient and graft survival rates were observed with both treatments. CONCLUSIONS: Thymoglobulin was found to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.

The impact of pre-transplant obesity on renal transplant outcomes.

The impact of obesity on graft survival after renal transplantation continues to be controversial. We have reviewed our experiences with living donor and cadaver transplantation in the current decade, focusing specifically on the impact of obesity on transplant outcome. Preoperative body mass index (BMI, kg/m2) was calculated for all adult renal transplant recipients between January 1990 and December 1995 and was used to classify patients as non-obese, moderately obese or morbidly obese. The effect of the degree of obesity on early and late outcomes after renal transplantation was examined. Three hundred and thirty-three recipients had pre-transplant BMI < 30 (normal or mild obesity), 68 BMI 30-40 (moderate obesity), and 7 BMI over 40 (morbid obesity). There was no correlation between obesity and other demographic factors. Wound infections and delayed graft function occurred more commonly in moderately and morbidly obese than in other cadaver donor recipients. Obese patients gained more weight after surgery and were given lower doses per kilogram of cyclosporine. There was, however, no significant correlation between obesity and graft survival for either cadaver or living donor transplants. Although obese patients have an increased risk of delayed graft function with cadaver donor transplantation, obesity has no discernible impact on either immunologic or overall graft survival with cadaver or living donor transplantation. The impact of moderate obesity on transplant outcome is modest and should not prevent these patients from receiving a transplant.