Informatics Publishing Limited

Asha Moudgil ¹, Charu Gupta ²

Affiliations
1 1.5-100, West Wing Department of Nephrology Children’s National Medical Center 111, Michigan Avenue, NW Washington, DC, 20010, US
2 Department of Nephrology, Children’s National Medical Center, Washington, DC, US

Abstract

Induction therapy is used to manipulate transplant recipients’ immune system to prevent acute rejection (AR) and immune mediated graft loss in the first few months. Historically, potent induction targeted at T-cells was used until maintenance immunosuppression could take effect. With modern maintenance immunosuppression, improved human leukocyte antigen (HLA) typing, cross-match and precise identification of anti-HLA antibodies, AR incidence has fallen significantly except in high-risk patients. Therefore, an increased need for devising targeted induction based on risk stratification for AR including targeting B-cells and complement has been recognized. Specific induction protocols are needed in children with end-stage renal disease (ESRD) due to focal segmental glomerulosclerosis (FSGS) and atypical hemolytic uremic syndrome (aHUS) to prevent disease recurrence. Induction is modified to avoid long-term steroids and to minimize nephrotoxic calcineurin inhibitor (CNI) exposure. Current data suggests that anti-interleukin-2 receptor and lymphocyte depleting antibodies may improve short-term graft survival in standard-risk and high-risk patients respectively; though effect on long-term graft survival has not been shown. In highly sensitized and those with a positive cross-match or ABO incompatible transplants, treatment with intravenous immunoglobulin, plasmapheresis and rituximab may be indicated. In children with ESRD due to FSGS and aHUS, pre-transplant plasmapheresis is useful. Eculizumab has replaced plasmapheresis in children with aHUS. Extended anti-IL-2R therapy or Thymoglobulin have been useful for steroid avoidance and Alemtuzumab for immunosuppression minimization. Belatacept induction and maintenance to avoid CNI use is under investigation. Tolerance protocols including recipient T-cell depletion and donor bone marrow or stem cell infusions are under way.

Keywords

Thymoglobulin, Basiliximab, Intravenous Immunoglobulin, Rituximab

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