Improving Access to HLA-Matched Kidney Transplants for African American Patients

Abstract

IntroductionKidney transplants fail more often in Black than in non-Black (White, non-Black Hispanic, and Asian) recipients. We used the estimated physicochemical immunogenicity for polymorphic amino acids of donor/recipient HLAs to select weakly immunogenic kidney transplants for Black vs. White or non-Black patients.MethodsOPTN data for 65,040 donor/recipient pairs over a 20-year period were used to calculate the individual physicochemical immunogenicity by hydrophobic, electrostatic and amino acid mismatch scores (HMS, EMS, AMS) and graft-survival outcomes for Black vs. White or vs. non-Black recipients, using Kaplan-Meier survival and Cox regression analyses. Simulations for re-matching recipients with donors were based on race-adjusted HMS thresholds with clinically achievable allocations.ResultsThe retrospective median kidney graft survival was 12.0 years in Black vs. 18.6 years in White (6.6-year difference; p>0.001) and 18.4 years in non-Black (6.4-year difference; p>0.01) recipients. Only 0.7% of Blacks received transplants matched at HLA-A/B/DR/DQ (HMS=0) vs. 8.1% in Whites (p<0.001). Among fully matched Blacks (HMS=0), graft survival was 16.1-years and in well-matched Blacks (HMS ≤ 3.0) it was 14.0-years. Whites had 21.6-years survival at HMS ≤ 3.0 and 18.7-years at HMS ≤ 7.0 whereas non-Blacks had 22.0-year at HMS ≤ 3.0 and 18.7-year at HMS ≤ 7.0, confirming that higher HMS thresholds produced excellent survival. Simulation of ABO-compatible donor-recipient pairs using race-adjusted HMS thresholds identified weakly immunogenic matches at HMS=0 for 6.1% Blacks and 18.0% at HMS ≤ 3.0. Despite prioritizing Black patients, non-Black patients could be matched at the same level as in current allocation (47.0% vs 56.5%, at HMS ≤ 7.0).ConclusionsRace-adjusted HMS (EMS, AMS)-based allocation increased the number of weakly immunogenic donors for Black patients, while still providing excellent options for non-Black recipients.

Canadian Kidney Transplant Professionals’ Perspectives on Precision Medicine and Molecular Matching in Kidney Allocation

“…Previous studies have shown that HLA matching is harder for Black transplant patients. 27 , 33 Lemieux et al 7 have outlined strategies to improve utility and equity in access to transplantation when incorporating molecular compatibility in organ allocation schemes for nonsensitized and sensitized patients, respectively. In the case of sensitized patients, this strategy aligns with the Eurotransplant Acceptable Mismatch program.…”

Comparative Study of the Impact of Human Leukocyte Antigens on Renal Transplant Survival in Andalusia and the United States

“…Some studies conclude that the best HLA matches occur when the donor and recipient are of the same race when the transplant comes from a cadaveric donor [37]. In addition, a recent study [38] indicated that HLA-based allocation systems disadvantage Afro-American patients, and this trend has been ongoing for decades [37]. The study reveals that HLA matching is more difficult for Afro-American patients than for white patients, with a lower likelihood that an Afro-American recipient will receive a transplant from a donor with a zero HLA mismatch.…”

Association of Recipient APOL1 Kidney Risk Alleles With Kidney Transplant Outcomes

“…In a recent study, using Organ Procurement and Transplantation Network data for 65 040 donor/ recipient pairs during a 20-y period, it was shown that the retrospective median graft survival in Black recipients was 12.0 y versus 18.6 y in White recipients, 17.2 y for Hispanics and 17.1 y for Asian Americans. 2 AA recipients who were followed for 9 y posttransplant were found to be 1.8 times more likely to experience graft failure compared with White recipients 3 and were more likely to have delayed graft function (odds ratio = 1.63 [95% confidence interval, 1.54-1.73]; P < 0.001), a risk factor for poor allograft survival. 4 Likewise, having an AA kidney donor is associated with worse graft survival (adjusted hazard ratio [HR] = 1.64 [95% confidence interval, 1.24-2.17]).…”