Comparison of polyclonal induction agents in pediatric renal transplantation

Abstract

Collective pediatric data suggest that anti-T-cell induction therapy with polyclonal antibodies improves the outcome of both short- and long-term renal allograft survival. Polyclonal agents, including thymoglobulin (Thy), a rabbit anti-thymocyte globulin; Minnesota (horse) anti-lymphoblast globulin (ALG); and ATGAM, a horse anti-thymocyte globulin (ATG), all suppress B and T cells. While no specific T-cell subset marker exists to measure the adequacy of immunosuppression with polyclonal induction, flow cytometric analysis has been used to evaluate the suppression of CD3, CD4, and CD8 cells. Thy is currently undergoing pediatric trials at our center, and we have utilized ATG and ALG in previous pediatric induction protocols. ALG (20 mg/kg/day) and ATG (15 mg/kg/day) were administered over 10 days, whereas Thy (2 mg/kg/day) was given over 5 days. All inductions were accompanied by preoperative intravenous solumedrol (10 mg/kg) followed by oral prednisone (2 mg/kg/day) with taper. Preoperative (1.5 mg/kg/day) and post-operative (2 mg/kg/day) azathioprine was administered to patients receiving ALG or ATG. Mycophenolate mofetil (MMF) (1200 mg/m2/day) was given to the patients receiving Thy. Post-operative cyclosporin A (CsA) (14 mg/kg/day) was started (for all groups) once renal function permitted (creatinine < 50% of baseline with brisk urine output) (trough goal 150-250 ng/mL via HPLC). Values for CD3, CD4, and CD8 T cells were determined by flow cytometry in 2-18-yr-old renal transplant recipients, comparing the polyclonal induction agent utilized [Thy (n = 8), mean age 9.7 +/- 2.3 yr; ATG (n = 13), mean age 10.1 +/- 4.1 yr; and ALG (n = 9), mean age 9.3 +/- 3.7 yr] over days 2-10 post-induction. Data were expressed as the average percentage of cells remaining relative to the baseline T-cell subsets (day 1 = 100%), because of the large age variation present in basal T-cell subset values. The flow cytometric data suggest that 5 days of Thy appears to give an equal or greater peripheral blood T-cell suppression by day 10 than a 10-day course of either ATG or ALG.