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Current issues in pediatric transplantation.

D A Kelly1

  • 1The Liver Unit, Birmingham Children's Hospital NHS Trust, Birmingham, UK. Deirdre.Kelly@bch.nhs.uk

Pediatric Transplantation
|August 17, 2006
PubMed
Summary
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Pediatric solid organ transplant recipients face long-term side effects from immunosuppressants, including viral infections and organ damage. Optimizing immunosuppression strategies is key to improving quality of life and graft survival in these young patients.

Area of Science:

  • Pediatric Transplantation
  • Immunosuppression
  • Long-term Outcomes

Background:

  • Pediatric solid organ transplantation survival rates exceed 80%, necessitating focus on long-term quality of life and minimizing side effects.
  • Current intensive immunosuppressive regimens (cyclosporine, tacrolimus, mycophenolate mofetil, steroids) effectively prevent rejection but cause significant adverse effects like viral infections, renal dysfunction, hypertension, and stunting.
  • While cytomegalovirus (CMV) mortality is reduced, morbidity persists; Epstein-Barr virus (EBV) infections remain a concern, though post-transplant lymphoproliferative disease is manageable.

Purpose of the Study:

  • To review the long-term side effects of immunosuppressive therapy in pediatric solid organ transplantation.
  • To discuss current and emerging strategies for optimizing immunosuppression to improve patient outcomes.
  • To highlight challenges in managing adolescent transplant recipients and ensuring long-term graft survival.

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Main Methods:

  • Review of current immunosuppressive protocols and their associated toxicities in pediatric solid organ transplant recipients.
  • Analysis of strategies to mitigate side effects, including reducing calcineurin inhibitor doses and exploring steroid-free regimens.
  • Discussion of challenges related to viral infections (CMV, EBV) and post-transplant lymphoproliferative disease management.
  • Examination of the impact of immunosuppression on renal function, growth, and the development of de-novo autoimmune conditions.
  • Consideration of non-adherence and psychosocial factors in adolescent transplant care.

Main Results:

  • Intensive immunosuppression leads to substantial long-term side effects, including a 30% reduction in renal function with calcineurin inhibitors (cyclosporine, tacrolimus) and potential chronic renal failure.
  • Strategies like using IL-2 inhibitors with low-dose calcineurin inhibitors and renal-sparing agents (MMF, sirolimus) show promise in preventing renal dysfunction.
  • Steroid-free regimens may reduce stunting and renal issues but can increase the risk of de-novo autoimmune hepatitis.
  • Effective management of CMV and EBV, alongside strategies for post-transplant lymphoproliferative disease, is crucial for reducing morbidity.

Conclusions:

  • Optimizing immunosuppression in pediatric solid organ transplantation is vital to balance rejection prevention with minimizing long-term side effects.
  • Novel protocols, including steroid-free and reduced-intensity regimens, are essential for improving graft and patient survival.
  • Addressing adolescent non-adherence and psychosocial challenges is critical for long-term transplant success, especially during the transition to adult care.