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

Abstract

Introduction: Kidney 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.

Methods: OPTN 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.

Results: The 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).

Conclusions: Race-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.

Keywords: allocation; human leukocyte antigen; human leukocyte antigen mismatch; immunogenicity; kidney transplantation; race; transplant survival.

Figure 1

Distribution of donor/recipient immunogenicity among Black and non-Black recipients. Patients were stratified either by HLA-A/B/DR mismatch (A) or by average HLA-A/B/DR/DQ HMS level (B). Class I immunogenicity as HLA-A/B antigenic mismatch distribution is shown in (C), and class II is shown as distribution of mismatches in HLA-DQ (D) and -DR (E) panels. Finally, panel (F) shows distribution of HLA-DR/DQ HMS scores. The dotted line represents the proportion of non-Black and Black recipients in the cohort.

Figure 2

Kaplan-Meier death-censored survival estimates for deceased donor kidney allograft in cohort patients stratified by recipient race (A, B) and summary of their median survival with 95% confidence intervals (C). Median death-censored graft survival (graft half-lives) in Blacks (D), Whites (E) and non-Blacks (F) measured in various immunogenicity categories defined HLA-A/B/DR/DQ HMS less than or equal to integer cutoff values from 0 to 10 are shown. Each immunogenicity category includes all patients with HMS scores below its threshold, which means each category overlaps with categories under lower HMS thresholds. Death-censored graft survival in Black patients (G), as well as White (H) and all non-Black patients (I) stratified by antigenic HLA mismatch is shown. Arrows show acceptable HMS values associated with the good transplant survival.

Figure 3

Percent of different ethnicity patients who receive a transplant under the indicated HMS threshold using current allocation vs. simulated allocation with priority for Black recipients. Bar graphs represent the percent of patients of various races who received a transplant under the indicated HMS threshold. The percent of patients who receive a transplant under current allocation policy (grey bars) vs. simulated allocation with the priority for Black patients (black bars).