Use of Antithymocyte Globulin for Reversal of Acute Allograft Rejection

SUMMERY A prospective randomized study evaluating the effectiveness of antithymocyte globulin (ATG) for reversal of established rejection was undertaken in 20 recipients of related donor renal allografts. The patients were initially treated with azathioprine and prednisone. With the onset of acute rejection they were randomly assigned to additional treatment with either ATG or high-dose steroids. Eight of 10 patients treated with ATG had prompt reversal of acute rejection and have had no further evidence of rejection. Two of the patients had continuing evidence of rejection after several days of ATG treatment and therefore received high-dose steroids as well. One patient regained normal function but the second suffered repeated rejection episodes which eventually resulted in allograft failure All 10 patients treated with high-dose steroids had initial reversal of rejection, although four required irradiation of the graft and actinomycin therapy as well and five patients subsequently required treatment for second and third rejection episodes. One patient in this group died with perforated diverticulitis following reversal of rejection With a mean followup of 14 months, 9 of 10 patients treated with ATG have functional allografts, renal function being normal in 8 patients. Nine of 10 patients treated with steroids have functional grafts but renal function remains unpaired in three. The effectiveness of ATG when added at the time of acute allograft rejection has been demonstrated. The major advantage of ATG for rejection reversal has been a marked decrease in the cumulative steroid dose administered to these patients. This may avoid many long-term adverse effects of steroids such as the fatal diverticulitis complication observed in this study. An additional suggested benefit is a decreased incidence of second rejection episodes in the ATG-treated patients Heterologous antisera to human lymphocytes (e.g., antilymphocyte serum, antilymphocyte globulin (ALG), and ATG) have been used in conjunction with azathioprine and prednisone for primary immunosuppression following renal transplantation in multiple clinical trials. Despite their remarkable efficacy in experimental models, the usefulness of such preparations in improving long-term allograft function in man remains under investigation. Since it has been demonstrated in most animal models that ALS was more effective for suppression of primary rather than secondary immune responses, these agents have been even less extensively evaluated for the specific treatment of acute allograft rejection episodes Currently, most protocols for treatment of acute renal allograft rejection rely on increased steroid dosages with or without other agents such as radiation therapy and actinomycin D. Mee and Evans (1) and Deodhar et al. (2) used ALG in a nonrandom manner as an adjunct to such antirejection therapy and concluded that ALG did not add to the standard treatment. In two randomized studies, in which ALG was administered starting at the time of rejection, all patients received increased steroid dosages as well. Similarly, these studies did not demonstrate any significant long-term benefit of ALG when added to standard high-dose steroid therapy, although the patients receiving ALG did have fewer second rejection episodes (3) or had more rapid reversal of rejection (4). The present randomized controlled study was undertaken to define precisely the effectiveness of ATG alone as compared to increased steroids administered at the time of diagnosis of acute rejection