[Kidney transplantation in highly sensitized patients]

The broad alloreactivity of antibodies in patients awaiting renal graft is a barrier to access to transplantation and may be the cause of acute or chronic graft dysfunction. Proper management of highly sensitized patients allows safe graft transplant and reduced wait-ing time. First, serum profiles from the patients should be distributed to all transplant centers for typing to every well HLA-matched donor. Secondly, a precise profiling of antibodies must be made, including differentiation of autoantibodies and alloantibodies, and determining the levels and specificities of alloantibodies. Thirdly, only well-matched kidneys are to be transplanted, particularly important with regard to HLA-DR and HLA-B antigens. The identification of acceptable mismatches in HLA class I and class II antigens and defining the probability of a negative cross-match can help finding a donor. Fourthly, pretransplant cross-matching should be performed by a complement-dependent cytotoxicity method (CDC) with T and B lymphocytes and antihuman globulin augmentation (AHG-CDC), flow cytometry (FC), or immunoenzymatic assay (ELISA) with current and historical sera. The desensitizing protocols should be kept in reserve for highly sensitized patients who are unlikely to receive a graft. Two of these protocols are plasmapheresis/immunoadsorption with low doses of intravenous immune globulin anti-CMV (100 mg/kg b.w.) or high doses of immune globulin (2 g/kg b.w.). Immunosuppressive treatment should consist of decisive induction and maintenance of immunosuppression, e.g. with ATG, tacrolimus, and mycophenolate mofetil. The monitoring of anti-donor antibodies after transplantation is obligatory. The symptoms of antibody-mediated rejection are graft dysfunction, and characteristic pathologies including C4d staining, vasculitis, neutrophil infiltration, and circulating donor-specific antibody.