Transplanting the Highly Sensitized Patient: The Emory Algorithm

Abstract

Renal transplant patients sensitized to HLA antigens comprise nearly one-third of the UNOS wait-list and receive 14% of deceased donor (DD) transplants, a rate half that of unsensitized patients. Between 1999 and 2003, we performed 492 adult renal transplants from DD; 120 patients (∼25%) had a panel reactive antibody (PRA) of >30%, with nearly half (n = 58) having a PRA of >80%. Our approach is based upon highresolution solid-phase HLA antibody analysis to identify class I/II antibodies and a 'virtual crossmatch' to predict compatible donor/recipient combinations. Recipients are excluded from the United Network for Organ Sharing match run if donors possess unacceptable antigens. Thus, when sensitized patients appear on the match run, they have a high probability of a negative final crossmatch. Here, we describe our 5-year experience with this approach. Five-year graft survival ranged from 66% to 70% among unsensitized (n = 272), moderately sensitized (PRA < 30%, n = 100) and highly sensitized (>30% PRA; n = 120) patients, equal to the average national graft survival (65.7%). The application of this approach (the Emory Algorithm) provides a logical and systematic approach to improve the access of sensitized patients to DD organs and promote more equitable allocation to a highly disadvantaged group of patients awaiting renal transplantation.

HLA Antibody Detection With Solid Phase Assays: Great Expectations or Expectations Too Great?

“…By applying virtual crossmatching, highly sensitized patients, the most disadvantaged group of candidates awaiting kidney transplants, are being transplanted at a rate greater than at any time in the past. Furthermore, and in contrast to long held beliefs, graft survival in patients with high pretransplant PRA (or cPRA) values is essentially the same as unsensitized patients provided no DSA was present at the time of transplant or developed de novo (13,65). As a direct result of more accurate antibody analysis, a policy for national sharing of organs for patients who have a cPRA of 100% was recently approved for implementation by the end of 2014.…”

“…In 2006, investigators at Emory University and Duke University independently published results demonstrating the clinical applicability of virtual crossmatching for highly sensitized patients receiving deceased donor kidney (Emory) and lung (Duke) transplants (13,15). Subsequently, a retrospective analysis by UNOS evaluated the ability of virtual crossmatching to predict positive crossmatches among highly sensitized patients on the national waiting list and reported the positive predictive value to be >90% (20).…”

“…Just as importantly, if positive, the crossmatch would be interpreted as ''not due to HLA antibodies'' (2,12) and proceeding to transplant would be reasonable and practical (13,14), with the proviso that antibody analysis was comprehensive and up to date. The precise evaluation of HLA antibodies present in sera of sensitized patients coupled with objective identification of the HLA antigens expressed by organ donors defined the process of the vXM.…”

“…The precise evaluation of HLA antibodies present in sera of sensitized patients coupled with objective identification of the HLA antigens expressed by organ donors defined the process of the vXM. The implementation of the vXM has facilitated local, regional and national solid organ allocation from both deceased and living donors (13,(15)(16)(17)(18) and has been particularly beneficial to highly sensitized patients, that is, those with panel reactive antibody (PRA) !80%.…”

Bioengineering Priorities on a Path to Ending Organ Shortage

“…Considerable work has been done in optimizing patient matching to ensure equitable and efficient pairing between recipients and cadaveric donors with consideration for geographical and other disparities. Interested readers are referred to these references for additional viewpoints [33][34][35]. Finally, to fully optimize organ transport, a future system may include a centralized database that can seamlessly match donors (cadaveric or living) equitably with patients on the waiting list along with tracking technology to seamlessly communicate organ delivery times in a highly effective manner, perhaps even via an app that could be checked on a smart phone.…”