Renal Transplant

Renal Transplant - RENAL TRANSPLANTATION IN CHILDHOOD Lynne...

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RENAL TRANSPLANTATION IN CHILDHOOD Lynne P. Yao, M.D. INOVA Fairfax Hospital for Children Fairfax, VA
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Overview Review basic transplantation immunology Review immunosuppressive agents used in children Review clinical renal transplantation outcomes in children Review specific complications of renal transplantation in children Review the role of the general pediatrician in the care of a child with a renal transplant Review future directions in renal transplantation
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Historical perspectives 1902: First experimental kidney transplantation by Emerich Ullmann 1933: First human kidney transplant by Voronoy 1950-53: First functioning human kidney transplant (2 centers) 1961: Azathioprine first used successfully 1962: First use of tissue matching to select a donor 1963: Prednisolone and Azathioprine combination produced longer graft survival 1972: Successful transplantation into a 9 month-old girl 1978: First clinical use of cyclosporine A
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Transplant immunology ABO group matching Blood group mismatches result in hyperacute rejection in most cases ABO incompatible donor protocols underway in children Human Leukocyte Antigen (HLA) matching Panel Reactive Antibodies (PRA) and Crossmatching Rejection an immune response raised by the recipient against foreign (donor) alloantigens allograft rejection is a coordinated event
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HLA (Human Leukocyte Antigen) matching HLA system is divided into 2 classes Class I: HLA-A, HLA-B, HLA-C Expressed on most cell surfaces Class II: HLA-DR, HLA-DP, HLA-DQ Expressed predominantly on antigen presenting cells HLA-A, HLA-B, HLA-DR most important in clinical transplantation HLA genes located on short arm of chromosome 6 HLA antigens are inherited in a Mendelian fashion as codominant alleles
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Example of HLA matching A B DR Mother 3/29 13/44 5/7 Father 2/1 8/42 4/3 Patient 3 / 1 8 / 44 5 / 3 Result: Patient is a 3/6 antigen match with each parent (haplotype match) Haplotype matching improves graft survival because minor (unidentified) HLA loci are also matched HLA locus
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Crossmatching Used to detect presence of preformed HLA antibodies against donor tissues Lymphocytes from donor are incubated with recipient serum, complement added, and cell lysis is detected Positive crossmatch is associated with high risk for hyperacute rejection Prevents development of hyperacute rejection
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Panel reactive antibodies (PRA) PRA Used to assess likelihood of positive crossmatch Lymphocytes from a “representative” panel of donors are incubated with serum from patient Expressed as a percentage of panel cells showing activity High PRA levels are associated with greater likelihood of positive crossmatch Major risk factors for high PRA are prior blood transfusion, pregnancy, and prior transplant
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T lymphocyte activation from Arakelov, Lakkis, Semin. Nephrol., 20:2, 2000
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Renal Transplant - RENAL TRANSPLANTATION IN CHILDHOOD Lynne...

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