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Current issues in pediatric transplantation
Author(s) -
Kelly D. A.
Publication year - 2006
Publication title -
pediatric transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.457
H-Index - 69
eISSN - 1399-3046
pISSN - 1397-3142
DOI - 10.1111/j.1399-3046.2006.00567.x
Subject(s) - medicine , immunosuppression , tacrolimus , calcineurin , transplantation , sirolimus , rituximab , immunology , lymphoma
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.