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% in FCXM+ recipients, and ≤3.6% in complementdependent 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. *Corresponding author: Ralph J. Graff, 3635 Vista at Grand Blvd., St. Louis, MO, USA 63110-0250, Tel: 314-577-8647; Fax: 314-268-5126; E-mail: [email protected] Received December 01, 2011; Accepted January 11, 2012; Published January 13, 2012 Citation: Graff RJ, Duffy B, Xiao H, Radell J, Lentine KL (2012) The Role of the Crossmatch in Kidney Transplantation: Past, Present and Future. J Nephrol Therapeutic S4:002. doi:10.4172/2161-0959.S4-002 Copyright: © 2012 Graff RJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Introduction Since Murray’s successful transplant of an allogeneic kidney in 1959 [1], renal transplantation has evolved from an experimental technique into an accepted modality for the treatment of end-stage renal disease with more than 310,000 renal transplants having been performed by 2010 [2]. This achievement constitutes a classical example of multidisciplinary collaboration: the description of the rejection of canine allografts by a surgeon [3], the appreciation by geneticists that the targets of rejection are inherited [4,5], the elucidation of the mechanism of allograft rejection by biologists [6], and the adaptation of this knowledge to the bedside by clinicians [1,7]. The two mechanisms employed to minimize transplant loss from rejection are the suppression of the recipient immune response with medications and immunogenetic characterization of the recipient. Early immunosuppressive medication regimens allowed transplantation of un-sensitized recipients, but transplantation of sensitized recipients was associated with immediate and early graft rejection. The most aggressive anti-rejection drug regimens available could not save these kidneys. The utilization of a complement dependent microcytotoxicty crossmatch (CDCXM) (an assay that measures cell bound antibody by its ability to bind complement and cause cell lysis) allowed the identification of recipient pre-sensitization to the donor kidney [8] as well as the recognition of the association between a CDCXM+ result and immediate graft loss [9], allowing an avenue for its avoidance. Over the last 50 years, as a result of improvement of immunosuppressive drug regimens and immunological evaluation techniques, kidney transplant outcomes have been greatly improved. The objective of this report is to review the evolution of crossmatch technique and associations with kidney transplant outcomes. Specifically, we review kidney graft outcome data in CDCXM, flow cytometry crossmatch (FCXM) and virtual crossmatch (VXM) negative (–) and positive (+) kidney transplant recipients. In several instances we updated our prior analyses using more recent Standard Transplant Analysis and Research Files (STAR) provided by the Organ Procurement and transplant Network (OPTN). We also review the role of antibody reduction therapy and post-transplant monitoring. The Evolution of Crossmatch Technology Because rejection-associated graft loss was observed in CDCXM– recipients [9], the initial CDCXM was refined to improve immunologic characterization of the recipient through the use of separated T and B lymphocyte target cells [10], the addition of wash steps [11], extended incubation [12], and the use of anti-human globulin (AHG) augmentation [12,13]. Flow cytometry technology was adapted to create a FCXM [14]. The flow cytometer measures cell-bound antibody with a fluorescing label, the amount of antibody being quantified by fluorescence intensity. The unit of intensity is called a channel, and the difference between control and experimental is called channel shift. Although each laboratory sets its criteria for a positive test, a 40 channel shift for T cells and an 80 channel shift for B cells are Citation: Graff RJ, Duffy B, Xiao H, Radell J, Lentine KL (2012) The Role of the Crossmatch in Kidney Transplantation: Past, Present and Future. J Nephrol Therapeutic S4:002. doi:10.4172/2161-0959.S4-002