Brennan DC, et al. "Rabbit antithymocyte globulin versus basiliximab in renal transplantation". New England Journal of Medicine. 2006. 355(19):1967-1977.
How does induction with antithymocyte globulin compare to basiliximab for high-immunologic risk kidney transplant recipients?
Antithymocyte globulin was associated with lower rejection rates and rejection severity at 12 months when compared to basiliximab induction in high-risk kidney transplant recipients. The incidence of delayed graft function, patient survival and graft survival were similar between groups.
Antibody induction therapy is used in a majority of kidney transplant recipients to reduce risk of acute rejection and delayed graft function, both of which negatively influence graft survival.  Antithymocyte globulin is a rabbit-derived polyclonal antibody which exerts its affect across multiple immunologic targets and depletes T-lymphocytes. Basiliximab is a chimeric, monoclonal antibody which specifically inhibits the interleukin-2 receptor, blocking downward replication of T-lymphocytes, but it does not deplete them. Given that previous studies with antithymocyte globulin have showed reduced rates of delayed graft function with 7-14 day courses of therapy, and other studies have shown similar rejection rates with shorter vs longer courses of therapy, this study aimed to evaluate if a shorter course of antithymocyte globulin would be a superior to induction with basiliximab in high- risk kidney transplant recipients.
This international, multicenter, randomized controlled trial evaluated a 5-day course of thymoglobulin vs basiliximab induction in patients deemed highest risk for acute rejection and delayed graft function. There was no difference in the primary composite endpoint of acute rejection, delayed graft function, graft loss or death. However, overall rejection rates and severe rejection rates were significantly lower in the antithymocyte globulin-treated patients when compared to basiliximab-treated patients. Individual components of the composite (delayed graft function, graft loss and death) were not different between groups. There were lower rates of rejection in black and nonblack subgroups with antithymocyte globulin, but only the comparison within nonblack patients was statistically significant. Leukopenia and infections were more common in the antithymocyte globulin-treated patients. However, rates of cancer, serious adverse events were similar between groups. Notably, the rate of CMV infection was lower in the anti-thymocyte group.
This study demonstrates improved rejection rates, but similar rates of delayed graft function, with antithymocyte globulin vs. basiliximab in high-risk patients. At least one other study demonstrated superiority of antithymocyte globulin with regards to rejection and delayed graft function, when compared to an interleukin-2 receptor antagonist in a high-risk population.  Other studies, including a meta analysis that have compared antithymocyte globulin to basiliximab and have found no difference have been in low-risk or general populations.  Longer term randomized controlled trials may be needed to determine if either induction agent influences longer term graft survival, however a UNOS registry data review by Cai and Terasaki of over 100,000 kidney transplant recipients showed that antithymocyte globulin had improved 5-year graft survival vs. basiliximab.
Primary outcome: composite of the first occurrence of biopsy-proven acute rejection, delayed graft function, graft loss or death at 12 months.
Cyclosporine was started when urine output ≥1.5L/day for 2 consecutive days; serum creatinine was ≤3.0 mg/dL for 2 consecutive days; or serum creatinine decreased to <50% pre-transplant level.
If cyclosporine was started later than post-operative day 4, it had to be within "therapeutic range" by post-operative day 10.
Comparisons are antithymocyte globulin vs. basiliximab.
This study was supported by SangStat Medical Corporation and Genzyme.
↑ Cecka JM, Cho YW, Terasaki PI. "Analyses of the UNOS Scientific Renal Transplant Registry at three years--early events affecting transplant success." "Transplantation." 1992;53:59-64.
↑ Brennan DC, Flavin K, Lowell JA, et al. "A randomized, double-blinded comparison of Thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients." "Transplantation." 1999;67:1011–8.
↑ Agha IA, Rueda J, Alvarez A, et al. "Short course induction immunosuppression with thymoglobulin for renal transplant recipients." "Transplantation." 2002;73:473–5.
↑ Noël C, Abramowicz D, Durand D, et al. "Daclizumab versus antithymocyte globulin in high-immunological-risk renal transplant recipients." "Journal of the American Society of Nephrology." 2009;20:1385–92.
↑ Liu Y, Zhou P, Han M, et al. "Basiliximab or antithymocyte globulin for induction therapy in kidney transplantation: a meta-analysis." "Transplant Proceedings." 2010;42:1667-70.
↑ Cai J, Terasaki PI. "Induction immunosuppression improves long-term graft and patient outcome in organ transplantation: an analysis of United Network for Organ Sharing registry data." "Transplantation." 2010;90:1511–5.
This page was last modified on 23 January 2019, at 14:40.