[Low-dose antithymocyte globulins in kidney transplantation: results of a protocol of intermittent administration].

BACKGROUND

Despite the long history of use of antithymocyte globulins (ATG) in renal transplantation, ideal doses and duration of ATG administration based on the monitoring of T lymphocytes have yet to be defined.

METHODS

Two immunosuppressive regimens based on low dose rabbit ATG (thymoglobuline, Imtix-Sangstat, Lyon-France) were assessed during the first year post-transplant: daily ATG (n = 32) where 50 mg of ATG were given every day and intermittent ATG (n = 24) where similar doses of ATG were given for the first three days and then intermittently only if CD3+T lymphocytes (measured by flow cytometry) were > 10/mm3. Both groups received steroids, azathioprine and cyclosporin A (CsA).

RESULTS

ATG-induced depletion was similar for PBL and T cells in both groups: it began at day one post-transplant, was submaximal at day 3 and reached maximum intensity between days 6 and 8 from which time cell counts progressively increased. However, T cell depletion was still present at day 20. The total ATG dose per patient (361 +/- 105 vs 556 +/- 119 mg/patient) and the mean cumulative daily dose of ATG (0.60 +/- 0.17 vs 0.80 +/- 0.14 mg/kg/d) were significantly lower in the IATG group (p = 0.0001, and 0.0006 respectively). The overlap of ATG and CsA treatment was 6.7 +/- 3 vs 7.4 +/- 4.3 days (p = ns) and the mean duration of ATG therapy was 12 +/- 3 vs 11 +/- 2.5 days in the IATG and DATG groups respectively (p = ns). ATG were given in an average of one dose every 1.6 days in the IATG group compared to one dose daily in the DATG group (p = 7 x 10(-7). There was no significant difference in renal graft function, the number of acute graft rejections or ATG related side effects and complications. Despite daily immunological follow-up, there was a net saving of 920 $/patient in the cost of treatment in the intermittent ATG group.

CONCLUSION

Intermittent ATG had the advantage of a reduction in the dose of ATG and in the cost of treatment while offering similar T cell depletion and effective immunosuppression. This approach could be proposed as an induction protocol, particularly for patients with poor graft function in whom CsA introduction has to be delayed.