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Efficacy of Single High-dose Intra-operative Anti-T-lymphocyte Globulin Induction: A Single Centre Analysis of Results after Kidney Transplantation between 1987 and 2004

Keywords: kidney transplantation , induction , ATG-Fresenius , patient survival , graft survival , rejection , immediate graft function

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Abstract:

Aim/Background: About 90 years after beginning of the era of polyclonal anti-lymphocyte antibodies, initiated by the work of Metchnikoff (1899) and 24 years after their first clinical testing by Starzl et al. (1966), we introduced in 1990 the intra-operative high-dose ATG-Fresenius (ATG-F) induction in addition to the triple-drug therapy (TDT) consisting of steroids, azathioprine and cyclosporine. This was a new prophylactic option to improve results after kidney transplantation.Material/Methods: This retrospective analysis presents data of all 778 first kidney transplantations from deceased donors, performed between 1987 and 1998. The results of standard TDT alone (1st group: TDT alone, n=216) were compared with those of two different ATG-F inductions (2nd group: n=78, 3 mg/kg body weight [bw] ATG-F on 7 or 8 consecutive days as multiple-dose starting intra-operatively,) 3rd group: n=484, 9 mg/kg bw ATG-F as single high-dose intra-operatively). Results: At the individual end of follow-up patient survival was 67.1% (1st group), 80.8% (2nd group) and 79.1% (3rd group) [groups 3 and 2 vs. 1: p=0.001 and p=0.023], respectively, whereas a comparison of the results of the Kaplan-Meier survival analysis did not show significant advantages for ATG-F during the first ten years. Graft survival with deceased patients counted as graft failures was 36.6% (1st group), 52.6% (2nd group) and 62.8% (3rd group) [groups 3 and 2 vs. 1: p<0.001 and p=0.014] at the end of follow-up. When comparing long-term kidney graft survival rates in the intra-operative single high-dose ATG-F induction groups with those of the group receiving TDT alone, Kaplan-Meier survival analysis revealed in a significant prolongation of graft survival. This result was independent of whether the analysis was performed counting deceased patient with a functioning graft as graft failures or censoring deceased patients with a functioning graft. In addition, significant differences regarding long-term graft survival in favour of ATG-F were also observed in pre-sensitized patients, in particular after single high-dose ATG-F induction. A total of 69% of the patients in the two cohorts receiving ATG-F were free of any rejection episodes compared to 56% of patients receiving only TDT (groups 1 and 2 vs. 3: p=0.001 and p=0.018). Conclusion: The analysis of 778 renal transplantations performed during 1987-1998 in one hospital clearly shows that ATG-F induction is safe and efficacious. In particular a single intra-operative infusion of 9 mg/kg bw ATG-F (high-dose) in addition to TDT was superior to TDT alone,

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