Impact of Small Variations in the Delivered Dose of Rabbit Antithymocyte Induction Therapy in Kidney Transplantation With Early Corticosteroid Withdrawal

Abstract

Optimal dosing of rabbit antithymocyte globulin (rATG) induction therapy in kidney transplantation is not well defined. The impact of dosing from variations in dose rounding or single dose limits has not been studied. This retrospective study of 242 adult renal transplant recipients receiving rATG induction and steroid-sparing maintenance therapy evaluates the effect of small changes in rATG induction dosing. The local protocol calls for four doses of rATG 1.5 mg/kg, approximated to the nearest 25 mg and limited to a max of 150 mg. Patients were stratified by total rATG dose received 5 to 6 mg/kg (n=151) and 6 mg/kg (n=91) or more. Incidence of biopsy-proven acute rejection, patient and graft survival, and allograft function were examined. Baseline and transplantation characteristics were similar between groups except for differences in mean weight (SD) (81 [17.3] vs. 76.3 [15.6]) and cumulative rATG dose received (451.8 [96.2] vs. 481.1 [93]) for patients in the 5- to 6-mg/kg group and 6-mg/kg or more group, respectively. Patients who received more rATG showed a significantly lower incidence of biopsy-proven acute rejection at last follow-up 11% (32/151) vs. 21.2% (10/91) among those who received only 5 to 6 mg/kg (P<0.042). Renal function (mean serum creatinine level) was similar at both 90 days and time of last follow-up. Safety review of leukopenia or thrombocytopenia did not differ. Small changes in total rATG induction administered seem to significantly impact the incidence of rejection. Adequate rATG dosing is associated with improved rejection-free graft survival and should be achieved for all patients; doses should be rounded up when appropriate or additional doses should be administered if necessary.