Current issues in pediatric transplantation.
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.
Kelly
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The Liver Unit, Birmingham Children's Hospital NHS Trust, Birmingham, UK. Deirdre.Kelly@bch.nhs.uk
D000293:Adolescent; D001828:Body Image; D002648:Child; D003586:Cytomegalovirus Infections / Q000175:diagnosis / Q000517:prevention & control; D020031:Epstein-Barr Virus Infections / Q000175:diagnosis / Q000517:prevention & control; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects / Q000379:methods*; D008297:Male; D016377:Organ Transplantation; D010349:Patient Compliance; D011247:Pregnancy; D011253:Pregnancy in Adolescence; D011788:Quality of Life