ANTILYMPHOCYTE THERAPY IN KIDNEY TRANSPLANTATION: A PROSPECTIVE RANDOMIZED TRIAL OF FULL-DOSE RABBIT ANTI-HUMAN THYMOCYTE GLOBULIN (RATG) VERSUS LOW-DOSE RATG AND BASILIXIMAB

P236 Aims: Antilymphocyte therapy by Rabbit Anti-human Thymocyte Globulin (RATG) may be used to increase immunosuppression in hyperimmune, second graft, or living donor renal transplant recipients, or to allow delayed cyclosporine (CsA) therapy in renal transplant patients with delayed graft function (DGF). Indeed, RATG is a powerful antirejection agent devoided of nephrotoxicity, but associated with an increased risk of acute adverse reactions and of chronic complications such as opportunistic infections and cancer. Monoclonal antibodies against the interleukin 2 receptor (basiliximab) are apparently devoided of these adverse effects, but are remarkably less effective in the prevention of graft rejection. Thus, combined therapy with low-dose RATG and basiliximab may serve to achieve the same antirejection activity of full-dose RATG, but with a better safety profile. Methods: In this randomized, prospective trial we compared the efficacy, tolerability and costs of treatment with full-dose RATG (2 mg/Kg) and low-dose RATG (0,5 mg/Kg) plus basiliximab (20 mg 4 days apart) in patients who received a kidney transplant in our Transplant Unit from October 2000 to September 2003. Both treatment protocols were started the day of transplant or of the first post-transplant dialysis session and were continued for 7 to 10 days. All patients received concomitant therapy with steroids, CsA and azathioprine or MMF. In those with DGF, CsA administration was stopped during RATG infusion. Results: Sixteen patients received full-dose RATG and 17 low-dose RATG plus basiliximab. Full vs. low RATG doses were associated with a higher prevalence of fever (56,5% vs. 17,6%; p = 0.01) and need of more red blood cell transfusions (2.0±2.38 vs. 0.53±0.94 units; p < 0.001) during RATG infusion, and with a higher incidence of CMV reactivation (56,5% vs. 17,6%; p= 0.01) over the follow-up period. Two acute rejections occurred on full-dose and 1 on low-dose RATG (p > 0.05). Time to first spontaneous serum creatinine decrease in patients with DGF (4 ± 2.8 vs. 5 ± 3.6 days; p > 0.05) and graft and patients survival (100% for both) were comparable in the two treatment groups. Average, per patient, treatment costs of full vs. low RATG doses plus basiliximab were 5400±1960 Euros vs. 3652±704 Euros, respectively (p=0.001). Conclusions: In renal transplant patients with an indication to antilymphocyte therapy low-dose RATG and Basiliximab are more cost-effective and better tolerated than full RATG doses alone.