HLA-B46 Homozygous Kidney Transplant Candidates Waitlisted with Bw4 and Bw6 Sensitization Have Not Been Transplanted Due to Limitations in US Allocation Policy

Aim: Among kidney transplant candidates, B46-homozygous candidates represent a unique population of individuals who often develop strong antibodies against two public epitopes, Bw4 and Bw6, leading to a calculated panel reactive antibody (CPRA) value of 99.98+%. We aimed to analyze US transplant registry data to measure access to deceased donor kidney transplant (DDKT) for these ultra-highly sensitized candidates, hypothesizing they would have exceptionally low transplant rates.

Methods: We extracted HLA typing data for historical deceased kidney donors and recipients from the Scientific Registry for Transplant Recipients (SRTR) listed since October 1, 2009 when CPRA was introduced in US allocation system. We then measured waiting time before delisting or kidney transplant for B46-homozygous candidates with CPRA>=99.9% and compared time to DDKT using Kaplan-Meier analysis with censoring for waitlist removal for non-DDKT reasons. We also identified DDKT from B46-homozygous donors, who represent the only HLA genotypes compatible with these ultra highly sensitized candidates.

Results: We found 206 US B46-homozygous candidates (114 candidates since 2009), and 34 of these candidates (11 males and 23 females; all Asian) had a CPRA of 99.9+% and were potentially Bw4+Bw6 sensitized. Strikingly, not a single one of these candidates through the end of 2022 received a DDKT, even though we identified 42 transplants from B46-homozygous deceased donors that went into other recipients (Figure 1). We further describe the key characteristics of B46-homozygous candidates and transplant recipients of B46-homozygous donors, such as removal descriptions and 0-ABDR antigen mismatch.

Conclusion: Our findings support that highly sensitized B46-homozygous candidates, most often identified as Asian and female, are disadvantaged in kidney allocation with disproportionately longer wait times. In future work we plan to analyze unacceptable antigen specificities and historical offer data to evaluate the order in which B46-homozygous donors were offered to candidates on the waiting list. We then plan to develop and test alternative allocation policies that would offer HLA-compatible donors to the ultra-highly sensitized candidates that are in greatest need, which would improve equity in organ allocation.