Current issues in pediatric transplantation

被引:51
作者
Kelly, D. A. [1 ]
机构
[1] Birmingham Childrens Hosp NHS Trust, Liver Unit, Birmingham, W Midlands, England
关键词
pediatric liver transplantation; immunosuppression; cytomegalovirus; Epstein-Barr virus; adolescence;
D O I
10.1111/j.1399-3046.2006.00567.x
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Pediatric solid organ transplantation is so successful that > 80% of children will survive to become teenagers and adults. Therefore, it is essential that these children maintain a good quality life, free of significant long-term side effects. While intensive immunosuppressive regimens (containing CsA, tacrolimus, MMF, and steroids) effectively reduce acute or chronic rejection, they can produce long-term side effects including viral infection, renal dysfunction, hypertension, and stunting. The development of effective methods of diagnosis, prevention, and treatment of CMV means that this is no longer a significant cause of mortality, but morbidity remains high. In contrast, infection rates of EBV remain high in EBV-negative pre-transplant patients. However, pre-emptive reduction of immunosuppression or treatment with rituximab or adoptive T-cell therapy is effective in preventing/treating post-transplant lymphoproliferative disease. Recent protocols have concentrated on reducing CsA immunosuppression, to prevent unacceptable cosmetic effects, and to reduce the hypertension, hyperlipidemia, and nephrotoxicity. Both CsA and tacrolimus cause a 30% reduction in renal function, with 4-5% of patients developing severe chronic renal failure. The use of IL-2 inhibitors for induction therapy with low-dose calcineurin inhibitors, in combination with renal-sparing drugs such as MMF or sirolimus for maintenance immunosuppression, should prevent significant renal dysfunction in the future. The concept of steroid-free immunosuppression with IL-2 inhibitors, tacrolimus, and MMF is an attractive option, which may reduce stunting and renal dysfunction. However, these regimens may be associated with the increased development of de-novo autoimmune hepatitis in 2-3% of children. The most important challenge to long-term survival in transplanted children is the management of non-adherence and other adolescent issues, particularly when transferring to adult units, as this is the time when many successful transplant survivors lose their grafts.
引用
收藏
页码:712 / 720
页数:9
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