Current issues in pediatric transplantation

Abstract

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.

Pediatric Vascularized Composite Allotransplantation

“…Retransplantation rates for chronic rejection vary between 5% and 25% for all organ types. 6 Of all transplant candidates on the waiting list in 2011, 5% to 9% were listed for retransplantation. 88 These are sensitized candidates who spend longer times on the waiting lists and are at higher risk for graft loss.…”

“…Among pediatric recipients of solid organ transplants, the cardiovascular disease risk factors are exponentially increased with the ensuing cardiovascular morbidities threatening both graft and patient survival 4,5 (Table 3). 6 Hypertension usually occurs within the first year after transplantation and persists into adulthood. 7 Older than 12 years at the time of transplantation, presence of intact native kidneys, at least 1 episode of acute rejection, and cadaveric allograft all correlate with an increased risk of developing hypertension after transplantation.…”

“…13 The efficacy of these regimens is demonstrated by the low retransplantation rates for chronic rejection, which vary between 5% and 25% for all organ types. 6 Interleukine-2 antagonists (basiliximab and daclizumab) remain the preferred induction agents in children given the higher risk of posttransplant lymphoproliferative disease (PTLD) and cytomegalovirus disease seen with T-cellYdepleting agents (antithymoglobulin and OK3). Calcineurin inhibitors are the main risk factors for posttransplant hypertension, with an increased risk when steroids are coadministered.…”

Trasplante hepático infantil. Resultados a largo plazo

“…Aunque los métodos de evaluación basados en creatinina sobreestiman, un 13% de los pacientes a los 5 años del trasplante presenta un filtrado glomerular inferior a 90 ml/min/1,73 m 217 . El 5% desarrolla insuficiencia renal terminal 39 .…”

Liver transplantation in children

“…O desen- Além disso, a incidência de rejeição aguda e crônica tem caído devido ao desenvolvimento de novas drogas imunossupressoras mais facilmente absorvidas, como a ciclosporina em microemulsão (Neoral), ou mais potentes, como o tracolimus 8 . O uso de terapia imunossupressora de indução com anticorpos monoclonais (inibidores de IL-2), como o daclizumab, um anticorpo humanizado, e o basiliximab, um anticorpo quimérico, com transferência para terapia imunossupressora de manutenção com drogas preservadoras da função renal, como o micofelonato mofetil ou o sirolimus (rapamicina), pode reduzir a disfunção renal a longo prazo 9 .…”