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Published on: April 12, 2021
Immunosuppressive Management of Pediatric Kidney Transplant Recipients
1Department of Pediatrics and Transplantation Center, University Hospital Motol, 2nd Faculty of Medicine, Charles University Prague and Biomedical Centre, Faculty of Medicine in Plzen, Charles University Prague, Plzen, Czech Republic.
Insights
Pediatric kidney transplant recipients require immunosuppression to prevent graft loss. Current strategies favor calcineurin inhibitors with antiproliferatives for maintenance, with individualized induction therapy based on risk.
Area of Science:
- Pediatric Nephrology
- Transplantation Immunology
Background:
- Kidney transplantation is the preferred treatment for pediatric end-stage kidney disease.
- Immunosuppressive medications are crucial for preventing rejection and graft loss in all transplant recipients, including children.
Purpose of the Study:
- To review current immunosuppressive strategies for pediatric kidney transplant recipients.
- To discuss the role of induction therapy, maintenance regimens, and treatment of acute rejection.
Main Methods:
- Literature review of recent advancements in pediatric kidney transplant immunosuppression.
- Analysis of current consensus and evidence regarding induction therapy, maintenance immunosuppression (CNIs, antiproliferatives, mTOR-inhibitors), and acute rejection management.
Main Results:
- No consensus exists for induction therapy in children; decisions should be risk-based.
- Maintenance therapy typically combines a calcineurin inhibitor (tacrolimus) with an antiproliferative (mycophenolate mofetil), with early or late steroid withdrawal in low-risk patients.
- mTOR-inhibitors are rarely used due to side effects and lack of proven benefit over CNIs. Therapeutic drug monitoring is essential for CNIs, mycophenolate, and mTOR-inhibitors.
Conclusions:
- Future research should focus on precise characterization of children needing induction therapy and specific indications for mTOR-inhibitors.
- The long-term goal is to achieve immune tolerance in pediatric kidney transplant recipients.
Abstract:
Kidney transplantation is a preferable treatment of children with end-stage kidney disease. All kidney transplant recipients, including pediatric need immunosuppressive medications to prevent rejection episodes and graft loss. Induction therapy is used temporarily only immediately following transplantation while maintenance immunosuppressive drugs are started and given long-term. There is currently no consensus regarding the use of induction therapy in children; its use should be decided based on the immunological risk of the child. The recent progress shows that the recommended strategy is to use as maintenance immunosuppressive therapy a combination of a calcineurin inhibitor (preferably tacrolimus) with an antiproliferative drug (preferably mycophenolate mofetil) with steroids that can be withdrawn early or late in low-risk children. The mTOR-inhibitors (sirolimus, everolimus) are used rarely in pediatrics because of common side effects and no evidence of a benefit over calcineurin inhibitors. The use of calcineurin inhibitors, mycophenolate, and mTOR-inhibitors should be followed by therapeutic drug monitoring. Immunosuppressive therapy of acute rejection consists of high-dose steroids and/or anti-lymphocyte antibodies (T-cell mediated rejection) or plasma exchange, intravenous immunoglobulines and/or rituximab (antibodymediated rejection). The future strategies for research are mainly precise characterisation of children needing induction therapy, more specific indications for mTOR-inhibitors and for the far future, the possibility to reach the immuno tolerance.
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