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 m 2 . 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.Until the late 1960s, renal transplantation in pediatric patients was a controversial service that was systematically provided in only a few centers. 1-4 Numerous ethical issues were raised at the outset, including risk to live donors, effects on family unity, mental health of well siblings, and doubts about the long-term prognosis.5 Some of these anxieties have been relieved with the passage of time. For example, complications associated with heavy steroid use have been progressively circumvented with better adjunct6 and/or baseline drugs7 -13 However, chronic immunodepression per se and drug-specific side effects (eg, nephrotoxicity) have remained the principal threats to the quality and duration of life of the pediatric recipient. 14 We report here an experience in 17 pediatric kidney recipients in whom the burden of longterm immunosuppression was lightened with a treatment regimen designed to avoid acute rejection while interfering minimally with natural tolerogenic mechanisms. 17 One principle of the strategy consisted of lymphoid depletion before renal allograft revascularization. In the first eight patients, the lymphoid depletion was done with antithymocyte globulin (ATG; Thymoglobulin R ). 18 In the next nine patients, alemtuzumab (Campath-1H ® )19 -23 was used. The second therapeutic principle consisted of the use of the least amount of post-transplant immunosuppression consistent with stable graft function. This was accomplished by beginning the postoperative course on tacrolimus monotherapy with subsequent attempts to reduce ...

Two Hundred Living Donor Kidney Transplantations Under Alemtuzumab Induction and Tacrolimus Monotherapy: 3-Year Follow-Up

“…(55), the experiences with this agent in renal transplantation have been promising (13)(14)(15)(16)18,(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)54,56). …”

Tolerance for organ recipients: A clash of paradigms

“…25 These principles have been applied in Pittsburgh since 2001 with encouraging results in liver and other organ recipients. [31][32][33][34] The same principles can be readily identified in the strategy reported by Donckier et al Immunosuppression was begun on the day of liver replacement. This consisted of 5 daily doses of antithymocyte globulin (ATG, thymoglobulin ), a 1-week course of mediumdose prednisone that was tapered at the time of stem cell infusion, and conventional doses of sirolimus until liver function normalized.…”

Alemtuzumab Pre-Conditioning With Tacrolimus Monotherapy in Pediatric Renal Transplantation

“…This regimen avoids posttransplant maintenance corticosteroids, which have had such deleterious effects on growth in children, and allows for low-dose tacrolimus monotherapy, to minimize nephrotoxicity. We recently reported on the early clinical experience with this regimen (4), and in this report describe a larger, more comprehensive experience with alemtuzumab pre-conditioning and tacrolimus monotherapy.…”