Antilymphoid antibody preconditioning and tacrolimus monotherapy for pediatric kidney transplantation

Abstract

Objective: Heavy post-transplant immunosuppression may contribute to long-term immunosuppression dependence by subverting tolerogenic mechanisms; thus, we sought to determine if this undesirable consequence could be mitigated by pretransplant lymphoid depletion and minimalistic post-transplant monotherapy.

Study design: Lymphoid depletion in 17 unselected pediatric recipients of live (n = 14) or deceased donor kidneys (n = 3) was accomplished with antithymocyte globulin (ATG) (n = 8) or alemtuzumab (n = 9). Tacrolimus was begun post-transplantation with subsequent lengthening of intervals between doses (spaced weaning). Maintenance immunosuppression, morbidity, graft function, and patient/graft survival were collated.

Results: Steroids were added temporarily to treat rejection in two patients (both ATG subgroup) or to treat hemolytic anemia in two others. After 16 to 31 months (mean 22), patient and graft survival was 100% and 94%, respectively. The only graft loss was in a nonweaned noncompliant recipient. In the other 16, serum creatinine was 0.85 +/- 0.35 mg/dL and creatinine clearance was 90.8 +/- 22.1 mL/1.73 m2. All 16 patients are on monotherapy (15 tacrolimus, one sirolimus), and 14 receive every other day or 3 times per week doses. There were no wound or other infections. Two patients developed insulin-dependent diabetes.

Conclusion: The strategy of lymphoid depletion and minimum post-transplant immunosuppression appears safe and effective for pediatric kidney recipients.

Figure 1

Course of a 15-year-old recipient of a maternal kidney. The patient was pretreated with ATG. The twice daily tacrolimus (Tac.) dose of 5 mg was consolidated to one 10 mg per day after 4 months. At 8.5 months, the dose was spaced to every other day and has remained at that frequency for 20 months (top panel). Because serum creatinine and creatinine clearance have been stable throughout, there have been no biopsies or additional treatment (bottom two panels).

Figure 2

Current immunosuppression at a mean follow-up of 22 ± 4.9 months in 16 patients with functioning kidneys. Of the 14 patients on spaced-weaning (88%), 11 have doses every other day and three are on a 3 times per week (Monday, Wednesday, Friday) schedule.

Figure 3

Height (Panel A) and weight (Panel B) for age and gender Z scores for the 16 patients who bear functioning grafts. Reference population data is from the 2000 Centers for Disease Control, growth data available online at www.cdc.gov/growthcharts.