The New Kidney Allocation System (KAS) and the Highly Sensitized Patient: Expect the Unexpected

OnDecember 4, 2014, theUnitedNetwork forOrganSharing (UNOS) and the Organ Procurement and Transplant Network (OPTN)will activate a newkidney allocation system (KAS) (1). After years of modeling, the new KAS is poised to improve allograft utility while minimizing the shortcomings of the current system. A critical facet of the new KAS focuses on the most disadvantaged candidates, namely, patients with calculated panel reactive antibody (cPRA) values of 98%, 99% and 100%. Compared to their less sensitized counterparts, these patients have prolonged wait times and a higher incidence of death on the wait list (http://srtr.transplant.hrsa. gov/annual_reports/2010/flash/01_kidney/index.html). In the new KAS, candidates with cPRA values of 98%, 99% and 100% have the highest priority to receive compatible deceased donor organs at the local, regional and national levels, respectively. That this aspect of the new KAS is possible is a testament to the success of bead-based, HLA antibody identification methodologies and virtual crossmatching, which, together, dramatically improved our ability to identify compatible donors for highly sensitized recipients (2,3). While the Scientific Registry of Transplant Recipients modeling of the new KAS predicts that patients with a cPRA of 98–100%will receive more transplant offers than ever before, there are two important issues not yet consideredwhich can negatively impact the process. First, in a recent survey of six transplant centers,more thanhalf of the 573 patients with cPRA values of 98–100% possessed antibodies toHLA-DPB,DPAandDQAantigens (BrayRAet al submitted for publication). Importantly, UNOS does not require deceased donors to be typed for the corresponding HLAantigens. Thus, laboratories and transplant programswill not have preallocation access to information that might lead to refusal of the offer. As such, we predict that a significant number of offers deemed ‘‘compatible’’ will likely be ‘‘incompatible’’ and crossmatches will be unexpectedly positive. Second, although all deceased donors are now HLA typed with molecular methodologies, typing errors still occur. Last year, as many as 4.5% of the typings reported to UNOSwerediscrepant (http://optn.transplant.hrsa.gov/CommitteeReports/interim_main_HistocompatibilityCommittee_ 9_5_2013_11_34.pdf). If a negative virtual crossmatch was predicted based on an erroneous HLA typing, a positive physical crossmatch could result in a canceled transplantwith the kidney being reallocated to a local back-up or shipped to another center. In either circumstance, ischemia time would be prolonged. Alternatively, the positive crossmatch could be misinterpreted as ‘‘not due to HLA antibodies,’’ leading to a transplantwith the potential for a disastrous clinical outcome. At present, there are no provisions that ensure the donor’s HLA type, reported to the UNet database, is correct. Accuracy in deceased donor typing is paramount when mandatory sharing of organs among the most highly sensitized patients is implemented. Improving accuracy may be as simple as requiring a second-level review before and after data are entered into the UNet database or as imposing as verification testing on a second sample from the same donor. Since the data are co-dependent, requiring a donor’s HLA type to be verified is as important as the requirement to verify the unacceptable antigens of recipients with cPRAs 98%. In summary, while the new KAS is a major step forward for the highly sensitized patient there are shortcomings in the process that should not be overlooked. UNOS and the OPTN have invested significant time, effort and financial resources to improve the kidney allocation process. Ignoring the practical issues discussed above is, in our opinion, ‘‘penny-wise, pound foolish. ’’ As it stands, when the new KAS is officially implemented and kidneys are mandatorily shared among highly sensitized patients, laboratories and transplant programsshould expect theunexpected.