Patients who are sensitized through pregnancy, previous blood transfusions, or organ transplantation produce donor-specific anti-HLA antibodies (DSA) that can result in an important obstacle in kidney transplantation. Sensitized patients wait longer on the cadaver donor transplant list, may not receive a transplant, and may have greater morbidity and mortality. Sensitized patients may have living donor candidates but transplantation cannot be performed because of cross-match positivity. Kidney transplant recipients with DSA are at higher risk of developing early acute antibody-mediated rejection (AMR) despite negative complement-dependent cytotoxicity (CDC) T-cell cross-match, and thus require desensitization. Desensitization protocols using the combination of apheresis (PE) or immunoadsorption to remove DSA and/or intravenous Ig (Iv-Ig) and rituximab to downregulate antibody-mediated immune responses have made kidney transplantation feasible by abrogating CDC T-cell cross-match positivity. All sensitized patients should be studied for DSA by sensitive methods and followed over time. The presence of DSA should be documented, and also the strength or titers of the alloantibodies should be determined to decide on the type of desensitization protocol. High-dosage Iv-Ig alone does not prevent AMR in patients with strong DSA, and the addition of peritransplantation PE as unselective plasma exchange, semiselective double filtration, or selective immunoadsorption significantly decreases the incidence of AMR. The effect of addition of monoclonal antibodies such as rituximab to desensitization protocols or of PE to patients with strong anti-HLA-II DSA on allograft outcomes requires further prospective studies.
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