The New OPTN Kidney Allocation Policy: Potential for Inequitable Access Among Highly Sensitized Patients

To the Editor: In 2013, the Organ Procurement and Transplantation Network approved a new national kidney allocation scheme (KAS) for deceased donor (DD) transplantation. Among the many attributes of the new policy was the decision to proactively address organ allocation to highly sensitized patients, long recognized to be the most disadvantaged group on the waiting list. Beginning on December 4, 2014, the new KAS will be implemented and candidates with calculated panel reactive antibody (cPRA) values of 98%, 99% and 100% will have the highest priority for local, regional and national sharing, respectively. This approach is projected to improve the access of patients in this group to compatible organs. While the new KAS undoubtedly favors the highly sensitized candidate, antibodies to HLA-DPB and HLA-DQA antigens were not incorporated into the new allocation algorithm and they were not (and could not be) modeled in the simulation performed by the Scientific Registry of Transplant Recipients. The effect of omitting this immunological information may have unintended consequences depending on the frequency of DPB and DQA antibodies among candidates with cPRA of ≥98%. Under the current allocation schema, listing of unacceptable antigens combined with virtual crossmatching has facilitated the transplantation of many highly sensitized patients (1.Cecka JM Kucheryavaya AY Reinsmoen NL Leffell MS. Calculated PRA: Initial results show benefits for sensitized patients and a reduction in positive crossmatches.Am J Transplant. 2011; 4: 719-724Abstract Full Text Full Text PDF Scopus (133) Google Scholar). Nonetheless, unexpected positive crossmatches still occur as a result of antibodies to DPB and DQA. In order to better understand the potential impact these antibodies may present under the new KAS, we assessed the frequency of antibodies to DPB and DQA among active candidates with cPRA ≥98%. Our findings show that these antibodies are quite prominent among this group of patients and we predict that their presence will result in a less-than-expected rate of transplantation. Data were collected on 593 waitlist (WL) candidates with cPRA ≥98% from six HLA laboratories encompassing 10 transplant centers (Emory University, Duke University, Henrico Doctor’s Hospital, Sentara Norfolk General Hospital, California Pacific Medical Center and Midwest Transplant Network (which includes five transplant centers: University of Kansas, The Children’s Mercy Hospital, St. Luke’s Health System, Research Medical Center and the University of Missouri)) and the frequency of antibodies against DPB and/or DQA were assessed. In addition, other parameters, such as average time on the WL, race, gender and whether the candidate was awaiting a primary or re-transplant were recorded. The data are summarized in Table 1. These highly sensitized candidates were predominantly females (65.5%), non-white minorities (73.7%), comprised ∼15.7% of active WL candidates and had a mean waiting time of 4.3 years. On average, 63% of WL candidates with cPRA ≥98% possessed antibodies against DPB and/or DQA (range 50–73%). This is not particularly surprising given that more than half of the candidates (53.7%) were awaiting a second or greater graft. Studies have shown that antibodies to DPB and DQA are common among sensitized candidates and recipients of failed renal allografts (2.Arnold ML Pei R Spriewald B Wassmuth R. Anti-HLA class II antibodies in kidney retransplant patients.Tissue Antigens. 2005; 65: 370-378Crossref PubMed Scopus (44) Google Scholar, 3.Duquesnoy RJ Awadalla Y Lomago J Retransplant candidates have donor-specific antibodies that react with structurally defined HLA-DR,DQ,DP epitopes.Transpl Immunol. 2008; 18 (et al): 352-360Crossref PubMed Scopus (75) Google Scholar, 4.Billen EV Christiaans MH Doxiadis II Voorter CE van den Berg-Loonen EM. HLA-DP antibodies before and after renal transplantation.Tissue Antigens. 2010; 75: 278-285Crossref PubMed Scopus (40) Google Scholar, 5.Tambur AR Leventhal JR Zitzner JR Walsh RC Friedewald JJ. The DQ barrier: Improving organ allocation equity using HLA-DQ information.Transplantation. 2013; 95: 635-640Crossref PubMed Scopus (40) Google Scholar). There was no significant difference between whites and non-whites with respect to the proportion of candidates with DPB and/or DQA antibodies.Table 1Characteristics of WL candidates with cPRA ≥98% from six HLA laboratoriesCenterN% of WL% F% Non-W% Re-TxAve. time on WL% w/Abs175127287554.8612230176277484.750338266878604.4714149186474534.957547107250623.073654115576444.168Total59315.765.573.753.74.363.3N, total number of candidates; WL, waitlist; F, female; W, White; Re-Tx, retransplant; Abs, combined frequency HLA-DPB and DQA antibodies. Open table in a new tab N, total number of candidates; WL, waitlist; F, female; W, White; Re-Tx, retransplant; Abs, combined frequency HLA-DPB and DQA antibodies. Although not a large study, our findings reveal that a majority of candidates with cPRA ≥98% possess antibodies against DPB and/or DQA antigens. Importantly, these antigens/loci are not considered in the new KAS, nor are they part of the current unacceptable antigen exclusion process. Kucheryavaya et al (6.Kucheryavaya A Tyan D Boyle G Kiger D Murphey C Baxter-Lowe L. A substantial increase in reporting of HLA-DPB typing of deceased donors in the U.S.Am J Transplant. 2014; 14: 590Crossref Google Scholar) recently reported that, as of September 2013, ∼29% of DDs were typed for DPB. This represents an increase from <1% in 2005, but still, only 51% of HLA laboratories are reporting DD typing information for DPB (6.Kucheryavaya A Tyan D Boyle G Kiger D Murphey C Baxter-Lowe L. A substantial increase in reporting of HLA-DPB typing of deceased donors in the U.S.Am J Transplant. 2014; 14: 590Crossref Google Scholar). The frequency of laboratories reporting DQA typing is not known. Thus, given the high frequency with which antibodies to DPB and/or DQA occur in candidates with cPRA ≥98%, combined with the lack of mandatory typing of DDs for these loci, we anticipate that the rate of unanticipated positive crossmatches will be high. The concern is that many highly sensitized candidates will not be transplanted with their allocated donor. Furthermore, one of the goals of the new KAS, namely, increasing access for highly sensitized candidates, will be viewed by some as having failed. Unsuccessful allocation due to HLA antibodies that were not accounted for could result in organs experiencing prolonged ischemia time as well as centers incurring unnecessary expenses for shipping and crossmatching. Thus, for many of the patients in this subgroup of highly sensitized candidates, the predicted increase in access will not likely be realized. In fact, the shortcoming of the algorithm actually creates an inequity among highly sensitized candidates, namely females and minorities, who appear to disproportionally present with antibodies to DPB and/or DQA. Moreover, since only about one-half of HLA laboratories perform DPB typing, transplant centers served by these laboratories may have an advantage over those centers whose laboratories do not provide this typing. In our opinion, an equitable solution would be mandatory typing of DPB (and possibly DPA) and DQA for all DDs, as well as full incorporation of HLA typing and all unacceptable antibodies into the allocation schema. Anything less will create an additional obstacle for a subset of already disadvantaged patients awaiting transplantation. The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.