The Role of the Crossmatch in Kidney Transplantation: Past, Present and Future

Immunogenetic characterization of the transplant recipient with crossmatch is used to minimize graft loss by detecting preformed antibodies. Use of increasingly sensitive tests including flow cytometry crossmatch (FCXM) has been accompanied by near elimination of hyperacute rejection. We reviewed associations of crossmatch results with kidney graft outcomes in contemporary practice, and provided updates of our past publications with more recent data in several instances. Recent United States registry data for transplants performed with a reported positive crossmatch demonstrate immediate graft loss rates of ≤1.3% or less in FCXM+ recipients, and ≤3.6% in complement-dependent cytotoxicity crossmatch positive (CDCXM+) recipients. One-year graft survival was reduced by ≤6.4% in FCXM+ versus FCXM- recipients, and by ≤11.5% in CDCXM+ versus CDCXM- recipients. Five-year graft survival was reduced by ≤10.2 % in FCXM+ versus FCXM- recipients, and by ≤8.7% in CDCXM+ versus CDCXM- recipients. A possible explanation for the markedly lower graft loss risk with crossmatch positive transplants in modern practice may be selection of recipients with low anti-HLA titers. Although a good correlation between virtual crossmatch and actual crossmatch has been demonstrated, the outcome significance of positive virtual/negative actual and negative virtual/positive actual crossmatches is not clearly established. Post-transplant demonstration of the persistence or appearance of donor-specific antibody is of value in prognostication, but utility for adjustment of therapy is uncertain. In summary, contemporary data suggest that, among selected transplants performed, the impact of a positive crossmatch may be relatively small compared to other accepted clinical factors. Further study is warranted work to determine, prospectively, under what circumstances crossmatch positive transplants can precede with safety.