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Thymoglobulin Induction Dosing Strategies in a Low-Risk Kidney Transplant Population: Three or Four Days?

DOI: 10.1155/2010/957549

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Abstract:

The optimal dose and duration of rabbit antithymocyte globulin (rATG) induction has not been defined. Methods. We compared the safety and efficacy of 2 dosing strategies, rATG 1.5?mg/kg for 4 days ( ) versus 2?mg/kg for 3 days ( ), in a retrospective, cohort study. Results. Two-year rejection-free survival was 95% in each group ( ). Renal function and infection rates were similar. The incidence of leucopenia was similar, although the 2?mg/kg group was more likely to be thrombocytopenic on day 2 (4% versus 28%, ). Length of stay tended to be longer for the 1.5?mg/kg group ( versus days ). A cost savings of $920 per patient for rATG were seen in the 2?mg/kg group ( ). Conclusions. Shorter, more intense dosing of rATG is safe and effective. The 3-day dose strategy resulted in a clinically shorter length of stay and may result in cost savings. 1. Introduction Induction therapy, using potent immunosuppressive agents in the critical, early period of allograft placement with the goal of decreasing the risk of acute rejection and potentially allowing lower overall intensity of the maintenance immunosuppressive regimen, is common in kidney transplantation. The induction agent of choice, along with dose and duration is controversial, center-specific, and often based on limited clinical data. Rabbit antithymocyte globulin (rATG, Thymoglobulin, Genzyme, Cambridge, MA) is FDA approved for treatment of acute rejection at a dose of 1.5?mg/kg for 7–14 days based on the results of a multicenter, double-blind randomized trial [1, 2]. Although rATG is not currently FDA approved as induction therapy in kidney transplantation, it is the most commonly administered agent for this purpose. Over one-half of the 70% of patients that receive an induction agent at the time of kidney transplantation receive rATG. Induction doses have ranged from 1–6?mg/kg/dose over 1–10 days with a more typical regimen of 1.5?mg/kg for 3–5 days [3–11] with a cumulative target of 4.5–10?mg/kg. In animal models, higher initial doses of shorter duration approximating a human-equivalent dose of 6?mg/kg were associated with more peripheral and central lymphocyte depletion and better allograft survival [12]. In humans, total doses of 5.7?mg/kg on average given as 1.5?mg/kg per day have been shown to produce similar outcomes in high risk recipients who received an average of 10.3?mg/kg [9]. Based on these models the optimal induction dose is felt to approximate 6?mg/kg [4, 7–10, 12]. Higher doses and prolonged duration of induction agents are thought to be associated with an increased risk of infection

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