1. EFFICACY AND SAFETY OF ANTI-THYMOCYTE GLOBULIN (ATG) TREATMENT OF STEROID RESISTANT ACUTE REJECTION IN KIDNEY TRANSPLANTATION
E. Bertoni, M. Biagini, M. Maccario*, G. Montagnino*, R. Piperno, A. Tarantino*, M. Salvadori
Renal Unit - Careggi University Hospital - Florence
*Renal Unit - Maggiore Hospital - Milano

2. BACKGROUND
DESPITE THE INTRODUCTION OF NEW ANTIREJECTION AGENTS, A SMALL NUMBER OF PATIENTS DEVELOPS REJECTIONS WHICH ARE RESISTANT TO STEROID THERAPY.SUCH REJECTIONS ARE A MAJOR CAUSE OF GRAFT LOSS IN TRANSPLANT RECIPIENTS. SEVERAL STUDIES REPORTED THAT RABBIT THYMOGLOBULIN MANUFACTURED BY IMTIX-MERIEUX IS SUCCESSFUL IN REVERSING 85% OF THIS KIND OF REJECTIONS

3. AIM OF THE STUDY
AIM OF THIS STUDY WAS TO VERIFY IN A RETROSPECTIVE STUDY THE EFFICACY AND SAFETY OF THYMOGLOBULINE MERIEUX (ATG) TREATMENT OF STEROID RESISTANT ACUTE REJECTIONS IN KIDNEY TRANSPLANTATION

4. PATIENTS AND METHODS I
WE REVIEWED THE CHARTS OF 34 RENAL TRANSPLANT PATIENTS (23 M, 11 F), MEAN AGE 41.73±11.59 YRS. ALL PATIENTS WERE ON CYA THERAPY GIVEN AS DUAL OR TRIPLE REGIMEN. ALL PATIENTS HAD A BIOPSY PROVEN ACUTE REJECTION WITH VASCULAR INVOLVEMENT (SCORE II-III).
MOST REJECTIONS OCCURRED IN THE FIRST PERIOD POSTTRANSPLANTATION (14.68±12.48 DAYS)

5. PATIENTS AND METHODS II
ALL PATIENTS GAVE AN INFORMED CONSENT TO RECEIVE THE DRUG. THIS WAS RECEIVED THROUGH A CENTRAL LINE. ALL PATIENTS AFTER UNSUCCESFULLY PULSE STEROID TREATMENT RECEIVED A 7-10 DAYS COURSE OF ATG WITH A DOSE RANGING FROM 1.5 TO 2.5 MG/KG ACCORDING THE REJECTION SEVERITY AND THE OCCURRENCE OF SIDE EFFECTS

6. RESULTS I
Most steroid resistant acute rejections occurred in the early post-transplant period (fig 1)
Serum creatinine levels during ATG treatment after a sharp increase by the 3rd day, decreased to mean levels of 2.07 mg/ml (fig 2)
Serum creatinine was well controlled also over the long term period.
This fact could be ascribed to the ATG pharmacokinetic and to the long term effect over the lymphocyte subsets (fig 3-4)

7. FIG. 1 NUMBER OF STEROID RESISTANT REJECTIONS BY TIME FROM TX

8. FIG. 2 SERUM CREATININE LEVELS IN THE ACUTE PHASE DURING TREATMENT WITH ATG

9. FIG. 3 THE DISAPPEARANCE CURVE OF RABBIT IgG IN THE PATIENTS SERUM OVER 3-MONTHS
From R.D. Guttmann, modified

10. FIG. 4 LYMPHOCYTE SUBSET COUNTS DURING AND AFTER ATG

11. RESULTS II
Main side effects were CMV infections, independently from the adopted prophylaxis and 3 cancers ( 2 Kaposi sarcomas ) completely reversed with the reduction of the immunosuppressive therapy (fig 5)
Graft 3 year survival rate was 80.36%, similar to the survival rate experienced by patients affected by severe acute rejections reversed by high dose of pulse steroid therapy (fig 6-7)
Patient 3 year survival rate was 96.7%.

12. FIG. 5 MAIN COMPLICATION PREVALENCE AFTER ATG TREATMENT
Fever (cytokine related) (84%)
CMV infection 9 (26.4%)
Cancer (9%)
Thrombocytopenia 5 (14.7%)

13. FIG. 6 ACTUARIAL GRAFT SURVIVAL AFTER ACUTE REJECTION TREATMENT WITH ATG

14. FIG. 7 ACTUARIAL GRAFT SURVIVAL AFTER ACUTE REJECTION TREATMENT WITH ATG OR STEROIDS
p= ns

15. CONCLUSION
OUR DATA SHOW THE EFFICACY AND THE SAFETY OF ATG TREATMENT IN STEROID RESISTANT ACUTE REJECTIONS WITH PROMPT RECOVERY OF RENAL FUNCTION IN THE MAJORITY OF PATIENTS.
THE RESULTS OBTAINED STABILIZED OVER A LONG PERIOD AFTER TREATMENT. PATIENTS AND GRAFT SURVIVAL RATES AT 3 YEARS WERE SIMILAR TO THOSE OF PATIENTS EXPERIENCING SEVERE ACUTE REJECTIONS CONTROLLED WITH STEROID TREATMENT ALONE