Jeremy M.Blumberg, Hans A.Gritsch, Elaine F.Reed, J.M.Cecka, Gerald S.Lipshutz, Gabriel M.Danovitch, Suzanne McGuire, David W.Gjertson and Jeffrey L.Veale
Incompatible donor/recipient pairs with broadly sensitized recipients have difficulty finding a crossmatch-compatible match, despite a large kidney paired donation pool. One approach to this problem is to combine kidney paired donation with lower-risk crossmatch-incompatible transplantation with intravenous immunoglobulin. Whether this strategy is non-inferior compared with transplantation of sensitized patients without donor-specific antibody (DSA) is unknown. Here we used a protocol including a virtual crossmatch to identify acceptable crossmatch-incompatible donors and the administration of intravenous immunoglobulin to transplant 12 HLA-sensitized patients (median calculated panel reactive antibody 98%) with allografts from our kidney paired donation program.…
Andrea A. Zachary, Mary S. Leffell
Summary: Desensitization protocols are being used worldwide to enable kidney transplantation across immunologic barriers, i.e. antibody to donor HLA or ABO antigens, which were once thought to be absolute
contraindications to transplantation. Desensitization protocols are also being applied to permit transplantation of HLA mismatched hematopoietic stem cells to patients with antibody to donor HLA, to enhance the opportunity for transplantation of non-renal organs, and to treat antibody-mediated rejection. Although desensitization for organ transplantation carries an increased risk of antibody-mediated rejection, ultimately these transplants extend and enhance the quality of life for solid organ recipients, and desensitization that permits transplantation of hematopoietic stem cells is life saving for patients with limited donor options. Complex patient factors and…
Annette M. Jackson, Mary S. Leffell, Robert A. Montgomery, and Andrea A. Zachary
Purpose of review
To identify factors that affect the choice of route to renal transplantation for the sensitized patient. The evolution of protocols for transplanting sensitized patients has been desensitization (DES), paired donation, and most recently, paired donation combined with DES. Use of these protocols has revealed various factors that influence which route is the most likely to work for a given patient.
The data indicate that patient blood type and HLA sensitization have the dominant influence on what route is best for a patient but numerous other factors, particularly the number, HLA type, and ABO type of donors a patient brings to a program will also affect the likelihood of transplantation. The distribution of these factors among patients transplanted or unable…
Robert A. Montgomery, Bonnie E. Lonze and Annette M. Jackson
Purpose of review
Many sensitized patients have willing live donors but are unable to use them because of a human leukocyte antigen (HLA) incompatibility. The options for these patients include: remaining on the deceased-donor list, entering a kidney-paired donation scheme, or undergoing desensitization with high-dose IVIg or plasmapheresis and low-dose IVIg.
Mathematical simulations verified by actual data from several national kidney-paired donation (KPD) programs has shed light on which donor/recipient phenotypes are likely to benefit from each transplant modality. Pairs that are easy to match are likely to receive compatible kidneys in a KPD. Those who are hard to match may be better served by desensitization. The phenotype which is both hard to match and hard to desensitize due to board and…
Annette M. Jackson, Edward S. Kraus, Babak J. Orandi, Dorry L. Segev, Robert A. Montgomery and Andrea A. Zachary
Rituximab has been used to increase the efficacy of desensitization protocols for human leukocyte antigen (HLA)-incompatible kidney transplantation; however, controlled comparisons have not been reported. Here we examined 256 post-transplant HLA antibody levels in 25 recipients desensitized with and 25 without rituximab induction, to determine the impact of B-cell depletion. We found significantly less HLA antibody rebound in the rituximab-treated patients (7% of donor-specific antibodies (DSAs) and 33% of non-DSAs) compared with a control cohort desensitized and transplanted without rituximab (32%
DSAs and 55% non-DSAs). The magnitude of the increase was significantly larger among patients who did not receive rituximab. Interestingly,…
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