CHAPTER 86: Transplant Protocols and Pharmacologic Considerations in the Pediatric Patient

INTRODUCTION

Management of the pediatric kidney transplant patient involves balancing the long-term health and outcomes of the transplanted organ with the potential risks for side effects, including infections, growth alterations, hypertension (HTN), diabetes, and malignancy. This chapter focuses on posttransplant treatment protocols and considerations specific to the pediatric patient. Although pediatric transplant management consensus guidelines do not exist, this chapter is based on data reported in the literature and consensus among various transplant centers.

Immunosuppression: The medications given to a patient during and after transplantation in order to lower the chance of the patient rejecting the kidney

• Goals of immunosuppression

  • Prevent rejection and improve kidney survival time

  • Minimize adverse effects, limit coinfections (viral, bacterial, or fungal), and avoid malignancies

TYPES OF IMMUNOSUPPRESSION

Induction

• Induction therapy is recommended for all kidney transplant recipients

• Consists of either a lymphocyte-depleting agent or an interleukin-2 (IL-2) receptor antagonist given before, during, or immediately after transplantation

• Corticosteroids are a standard part of induction protocols, and may be continued as a maintenance immunosuppressive as well

• Purpose of induction: To deplete or change the response of the immune system to the presenting antigen (the new kidney). Its use reduces the risk of acute rejection and allows for lower doses of initial maintenance immunosuppression

• The choice of induction agents used is based primarily on recipient characteristics (underlying disease, degree of sensitization, age, race, etc.), as well as donor–recipient match characteristics (human leukocyte antigen [HLA] mismatch, Epstein-Barr virus [EBV], and cytomegalovirus [CMV] positivity)

• IL-2 receptor antagonists: Basiliximab (Simulect)

  • Chimeric monoclonal antibody that binds to the IL-2 receptor preventing T-cell activation and proliferation

  • Initial dose given at time of transplant and then repeated on postoperative day 4

    • Patients less than 35 kg: 10 mg per dose

    • Patients 35 kg and greater: 20 mg per dose

  • Hypersensitivity to basiliximab is rare and therefore premedication is not necessary

• Lymphocyte depleting agents

• Rabbit antithymocyte globulin (Thymoglobulin, rATG)

  • Polyclonal antibody that binds to T-cell surface antigens and causes a depletion of CD4 lymphocytes

  • Initial dose is given at time of transplant and dosed daily for 4–7 days based on daily laboratory test results

    • Initial daily dose: 1.5 mg/kg

    • Consider dose adjustments for leukopenia, thrombocytopenia, and/or neutropenia Suggested Dose Adjustments

    Table Graphic Jump Location

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    	WBC count	Platelet count
    Decrease dose by 50%	2–3 × 103 cells/mm3	50,000–80,000/mm3
    Hold dose	< 2 × 103 cells/mm3	< 50,000/mm3

  • Premedication with corticosteroids, acetaminophen, and diphenhydramine required to prevent infusion related reactions

  • Central line administration preferred (if a peripheral line is used, medication should be mixed with heparin and hydrocortisone to prevent thrombophlebitis)

  • Administer through a 0.22-micron filter

  • Adverse effects: leukopenia and thrombocytopenia (requiring dose adjustments), cytokine release syndrome (requiring premedications), serum sickness, risk of infection, risk of malignancies

  • Equine antithymocyte globulin (Atgam, eATG)

    • Used less frequently, as ...