ABO-adjusted calculated panel reactive antibody (cPRA): A unified metric for immunologic compatibility in kidney transplantation

Abstract

Implementation of the kidney allocation system in 2014 greatly reduced access disparity due to human leukocyte antigen (HLA) sensitization. To address persistent disparity related to candidate ABO blood groups, herein we propose a novel metric termed "ABO-adjusted cPRA," which simultaneously considers the impact of candidate HLA and ABO sensitization on the same scale. An ethnic-weighted ABO-adjusted cPRA value was computed for 190 467 candidates on the kidney waitlist by combining candidate's conventional HLA cPRA with the remaining fraction of HLA-compatible donors that are ABO-incompatible. Consideration of ABO sensitization resulted in higher ABO-adjusted cPRA relative to conventional cPRA by HLA alone, except for AB candidates since they are not ABO-sensitized. Within cPRA Point Group = 99%, 43% of the candidates moved up to ABO-adjusted cPRA Point Group = 100%, though this proportion varied substantially by candidate blood group. Nearly all O and most B candidates would have elevated ABO-adjusted cPRA values above this policy threshold for allocation priority, but relatively few A candidates displayed this shift. Overall, ABO-adjusted cPRA more accurately measures the proportion of immune-compatible donors compared with conventional HLA cPRA, especially for highly sensitized candidates. Implementation of this novel metric could enable the development of allocation policies permitting more ABO-compatible transplants without compromising equity.

ABO‐adjusted cPRA metric for kidney allocation in an Asian‐predominant population

“…of each blood group also varies considerably between different localities and ethnic groups. 18,26 Contrast to the USA where blood groups A and B accounts for 37% and 12% in the donor pool, our local data showed that blood groups A and B each accounts for approximately 25% of the donors. Another difference is the higher percentage of blood group AB in Hong Kong than in the USA (7% vs. 3.5%).…”

“…With a population of 7.3 million (91.6% were Chinese), over 95% of the kidney donor pool in the ORTS of Hong Kong are of Chinese ethnicity, and due to such ethnic predominance the HLA allele/haplotype frequencies differ significantly from other populations and transplant programs 29,36–40 . Add to that, the phenotypic frequency of each blood group also varies considerably between different localities and ethnic groups 18,26 . Contrast to the USA where blood groups A and B accounts for 37% and 12% in the donor pool, our local data showed that blood groups A and B each accounts for approximately 25% of the donors.…”

“…The calculation of ABO‐adjusted cPRA (HK ABO‐cPRA) involved the frequencies of incompatible donor HLA antigens (conventional cPRA) and the frequency of incompatible donor ABO phenotype (Freq ABOi ). The ABO‐adjusted cPRA was computed according to the method reported previously, 26 the equation is: …”

“…A more efficient allocation system is required to achieve equity in transplant opportunities by reducing the biological disadvantage based on ABO incompatibility. Gragert et al recently published a unified metric for immunologic compatibility in kidney transplantation, incorporating both HLA sensitization and ABO blood group incompatibility in cPRA calculation 26 . One should appreciate that ABO frequencies varies with the ethnic composition of a population, and a unified HLA‐ABO metrics derived from a multi‐ethnic population such as the USA may not be fully applicable to localities where a single ethnic group is highly predominant (e.g., Asia‐Pacific regions).…”

“…Gragert et al recently published a unified metric for immunologic compatibility in kidney transplantation, incorporating both HLA sensitization and ABO blood group incompatibility in cPRA calculation. 26 One should appreciate that ABO frequencies varies with the ethnic composition of a population, and a unified HLA-ABO metrics derived from a multi-ethnic population such as the USA may not be fully applicable to localities where a single ethnic group is highly predominant (e.g., Asia-Pacific regions). In Hong Kong and various Asia-Pacific countries, ABO disparity is observed in the current organ allocation system and hence an ABO-adjusted cPRA metrics developed from local ABO and HLA frequency data is eagerly awaited.…”