Anti-thymocyte globulin (ATG) is used as induction immunosuppression in kidney transplantation to prevent allograft rejection. ATG causes dose-dependent lymphocyte depletion, yet optimal dose is unknown. ATG has a narrow therapeutic window between increased risks of rejection for under-dosing and infection for over-dosing.

Methods: We performed a retrospective analysis of sequential kidney transplants from 11/17/14 to 11/28/16. We collected data on covariates likely to confound the relationship between full or reduced ATG dose and kidney transplant outcomes. We performed descriptive statistics and multivariate logistic regression on 1 year outcomes. The a priori designated primary outcome was rejection-free graft and patient survival at 1 year.

Results: During the study period, 176 patients received kidney transplantation, 6 of whom had dual kidney-pancreas transplants. We excluded 16 patients who received basiliximab induction and 1 who died on post-operative day 1. Of 150 persons with complete data for 1 year follow-up, full dose ATG (>4.5 mg/kg) was given to 91 persons and reduced dose ATG (≤4.5 mg/kg) was given to 59 persons. Age, PRA, DSA and belatacept maintenance were associated with reduced ATG dose. Covariates associated with the primary outcome included race, prior transplant, steroid free at 30 days and leukopenia or thrombocytopenia within 5 days after transplant. Sex, deceased vs living donor, KDPI, use of pump, cold ischemia time and DGF were associated with neither the exposure nor the outcome. The primary outcome was achieved by 72 (79%) in the full dose group and 40 (68%) in the reduce dose group. In unadjusted analysis, the odds ratio (OR) for rejection-free graft and patient survival at 1 year was 0.56 (95%CI 0.26-1.17), p=0.12 in the reduced dose compared to full dose ATG groups. Adjusting for age, race, PRA, and positive DSA, the OR was 0.43 (95%CI 0.18-1.01), p=0.051. Only 44 (48%) and 19 (31%) of persons in the full and reduced ATG dose groups achieved a secondary outcome of rejection-free and infection-free graft and patient survival at 1 year.

Conclusion: Higher doses of ATG (>4.5 mg/kg) trended to improved outcomes for both rejection and infections. Treatment with ATG until achieving leukopenia or thrombocytopenia was associated with improved rate of rejection. Such blunt biomarkers for efficacy of ATG could potentially be improved on by a more specific biomarker such as CD3.

CITATION INFORMATION: Mitrokhin A., Goldman J., Trivedi B., Vidyasagar V., Vadivel N., Hart M. Optimal Anti-Thymocyte Globulin Dose for Induction Immunosuppression in Kidney Transplantation Am J Transplant. 2017;17 (suppl 3).

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