Antibody Testing Strategies for Deceased Donor Kidney Transplantation After Immunomodulatory Therapy

Background. Immunomodulatory protocols including intravenous immunoglobulin/rituximab (IVIG/R) are employed to decrease anti-human leukocyte antigen (HLA) antibody levels for patients broadly sensitized to HLA and increase chances for transplantation with a compatible deceased donor (DD). The aim of our study was to identify the optimal antibody levels allowing for selection of compatible DDs for these sensitized patients. Methods. From January 2006 to December 2009, 108 patients broadly sensitized to HLA who had reached the top of the DD waitlist were treated with IVIG/R. Antibody levels were monitored monthly by Luminex-based single-antigen bead assay. The antigens identified to produce positive complement-dependent cytotoxicity crossmatches (XMs; >200,000 standard fluorescence intensity [SFI]/10,000 median fluorescence intensity [MFI]) were determined to be unacceptable and entered into the United Network for Organ Sharing database generating the calculated panel reactive antibody (CPRA). The mean CPRA (mCPRA) for this group was more than 80. DDs were selected based on T-cell flow XMs (FXMs) less than 250 MCS and B-cell FXMs less than 300 mean channel shifts (MCS). Results. Monthly Luminex-based single-antigen assays showed that the IVIG/R therapy decreased antibody levels for a period of 30 to 120 days. Of the 108 patients treated, 80 (74%) were transplanted and 28 (26%) were not (mCPRA 96 +/- 11). Forty-two (53%) patients were transplanted with a positive FXM; 28 (35%) patients (mCPRA 84 +/- 25) were transplanted with a negative FXM; and 10 patients (12%; mCPRA90 +/- 19) received zero HLA ABDR mismatched grafts. Conclusions. After therapy, careful selection of acceptable DD involves the antibody profiling strength and XM results. These approaches provide patients broadly sensitized to HLA with an opportunity for compatible DD transplantation.