Kidney Transplantation Without a Final Crossmatch1,2

*Abbreviation: PRA, panel reactive antibody. The current United Network for Organ Sharing standards state that all prospective cadaver kidney transplant recipients should have a final crossmatch pretransplant (1). Yet in certain well-defined circumstances, the crossmatch is almost certain to be negative. Too often, waiting for the results of the crossmatch significantly postpones the transplant and increases the cold ischemia time. Increased cold ischemia time has been associated with increased risk of delayed graft function and with worse outcome (2,3). We hypothesized that potential recipients who have been regularly screened for anti-HLA antibodies against a panel of donor lymphocytes and who have been found to have no detectable antibodies (0% panel reactive antibody [PRA*]) are likely to have a negative crossmatch unless an intercurrent event stimulates antibody production. The aim of our current study was to determine whether patients on the transplant waiting list with a 0% PRA on their interval screening ever had a positive final crossmatch. We continue to think that the benefits of random donor, pretransplant transfusions outweigh the risks. Therefore, in general, we recommend that transplant candidates receive pretransplant transfusions. Exceptions include those who have known anti-HLA antibodies, those receiving HLA-identical living donor transplants, and those refusing transfusion. All transfusions are performed under azathioprine coverage. Transplant candidates are expected to send serum samples 4 to 6 weeks posttransfusion and at monthly intervals for PRA determination and for use in the screening and final crossmatch. The same technique (T-cell antihemophilic globulin) is used for PRA determination and for the screening and final crossmatches. We reviewed the records of 494 transplant candidates who had final crossmatches performed at the University of Minnesota between January 1, 1996, and December 31, 1997. Because we belong to a multicenter organ procurement organization encompassing three states, the preliminary screening crossmatches with peak and current sera were performed at a number of centers. The final crossmatch for first or second transplant candidates included all sera within the last 6 months plus a freshly drawn sample. The final crossmatch for third or fourth transplant candidates also included all historical sera. More recently, we have stopped transplanting recipients with historical positive crossmatches (4). Therefore, currently, for the final crossmatch, all historical samples plus a freshly drawn sample are used. Of the 494 candidates, 43 (8.7%) had positive final crossmatches; all 43 had previous positive PRAs. The mean (±standard deviation) PRA for those with final positive crossmatches (sample for each patient who had the lowest PRA and was crossmatch-positive) was 86.5±18.9 (range, 38-100%). Importantly, of the 494 candidates, 290 (58.7%) had no detectable antibodies to a panel of HLA antigens during their pretransplant screening (0% PRA). None of the 0% PRA patients had a final positive crossmatch. All 290 candidates with 0% PRA underwent transplantation. None had hyperacute rejection. The recognition that cytotoxic antibodies to donor cells could be responsible for immediate graft failure and the subsequent development of the crossmatch technique were major advances in clinical transplantation (5). The crossmatch rapidly became part of the routine pretransplant evaluation, but it soon became clear that not all antibodies identified by the standard crossmatch technique were immediately harmful to the graft (6-9). Considerable research has been conducted to determine when recipients with pretransplant antibodies can be successfully transplanted. However, little attention has been paid to whether the crossmatch is necessary for a 0% PRA transplant candidate. Cytotoxic anti-HLA antibodies occur most often after transplantation, pregnancy, and transfusions. Sanfilippo et al. (10) showed that transplantation and pregnancy were most likely to result in antibody production. Thus, we questioned whether in the absence of defined sensitizing events, a transplant candidate with a known 0% PRA would develop antibodies and have a final positive crossmatch. Our data suggested that such an event is unlikely. Kerman et al. (11) presented similar findings. This finding is of importance in that the transplant is often delayed for a final crossmatch, frequently setting off a domino effect that causes further delays. For example, an operating room that is available at the time the crossmatch is initiated may no longer be free when the crossmatch is completed. Moreover, transplantation without a final crossmatch would shorten the ischemia time. This is particularly beneficial for kidneys that have already had a relatively long ischemia time, such as a six-antigen-match kidney shipped from another part of the country. At most centers, when a potential cadaver donor is identified, a screening crossmatch is performed using sera from all (or a select group of) blood type-compatible recipients. Those who are crossmatch-negative are eligible to be called in as prospective recipients; when they arrive at the hospital, blood is drawn for a final crossmatch. On some occasions, both high- and low-PRA candidates are called in and it is necessary to wait to see if the high-PRA candidate has a negative final crossmatch. Under these circumstances, there is no time saved by not performing a final crossmatch for the 0% PRA candidates (but there may be costs saved). On other occasions, only 0% PRA candidates are called in. Under these circumstances, a final crossmatch may not be necessary. Our data raise two questions. First, is the screening crossmatch necessary in a patient with a 0% PRA and no intercurrent events that might stimulate anti-HLA antibodies? And second, with or without a screening crossmatch, is a final crossmatch ever necessary in such patients? Our data suggest that a final crossmatch is not necessary in select circumstances. We think that a patient with 0% PRA who can give an adequate history of no intercurrent events (e.g., transfusions) could be taken to the operating room without a crossmatch. Eliminating the final crossmatch for these selected patients would shorten preservation time and decrease the risk of delayed graft function. United Network for Organ Sharing guidelines should be changed accordingly. Acknowledgments. The authors thank Harriet Noreen and Miriam Segall for provision of the data and for discussion of the manuscript, the staff of the immunology laboratory who performed the assays, Mary Knatterud for editorial assistance, and Stephanie Daily for preparation of the manuscript.