CALCINEURIN INHIBITOR SPARING IN KIDNEY TRANSPLANTATION (CN-01)

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Improvements in post transplant care and immunosuppression have led to increasingly successful short-term outcome in pediatric recipients of kidney transplants. Unfortunately, morbidity associated with immunosuppressive agents is substantial and some of these drugs may accelerate chronic allograft nephropathy. The investigators propose that the use of the TOR-inhibitor, sirolimus, will obviate the need for calcineurin inhibitors in post-transplant immunosuppression in recipients of living donor grafts. If this pilot study is successful, the investigators will extend the protocol to include cadaver donor recipients and to a protocol including pre-transplant donor specific transfusions (DST) under sirolimus coverage. This deliberate pre-transplant exposure to donor antigen may lead to donor-immunosuppression even further. This long-term proposal is based on preclinical observations that DST plus T-cell costimulatory blockage (rapamycin) may result in activation induced cell death (AICD) of alloreactive T cells that are harmful to the graft. These protocols will include intense immunologic monitoring which is designed to uncover anti-donor responsiveness as early as possible. Patients will receive humanized anti-CD25 monoclonal antibody Dacluzimab, administered in 5 doses over a 2 month period. The first dose will be administered intra-operatively and the subsequent doses will be administered every two weeks up to 8 weeks post transplantation. Maintenance immunosuppression will also be administered beginning on Day -1.