ORGAN ALLOCATION AND TRANSPLANT EQUITY IN BRAZIL: THE HIDDEN BURDEN OF HLA HOMOZYGOSITY AND HYPERSENSITIZATION

Kidney transplantation remains the most cost-effective treatment for end-stage renal disease (ESRD), yet the global scarcity of donor organs leads to prolonged waiting times and disparities in access. In Brazil, despite a well-established public transplant program, immunological barriers such as HLA sensitization and homozygosity continue to limit transplant opportunities. The current allocation system prioritizes candidates based on ABO compatibility and mismatches at the HLA-A, -B, and -DR loci, but lacks specific policies for highly sensitized or homozygous patients. This study examined the impact of these factors on transplant probability to support potential improvements in allocation strategies.

This cross-sectional study evaluated kidney transplant recipients from deceased donors and active candidates on the Brazilian transplant waiting list between January 2010 and August 2024 in the regional sector of Minas Gerais. To identify factors most strongly associated with transplant status, a decision tree model was constructed, considering the variables sex, age group, diabetes mellitus status, immunological status, blood type, and homozygosity for HLA-A, HLA-B, and HLA-DR. The final tree included only the variables most strongly associated with the outcome, from which the cutoff point for immunological status was derived (cPRA ≥84). Model performance was assessed using accuracy. The study was approved by the Ethics Committee of the Faculty of Medical Sciences of Minas Gerais (CAAE: 65092117.0.0000.5134).

This study included 2,907 patients: 1,794 (61.7%) were transplanted and 1,113 (38.3%) remained active on the waiting list. The cohort was mostly male (60.4%) and under 60 years old (76.9%; mean age 49.3 ± 12.5). Hypertension (19.1%) and diabetes (12.1%) were the most common comorbidities. Blood types O (48.8%) and A (34.2%) predominated. Median cPRA was 0 [IQR: 0–11], with 7.7% ≥84. HLA-DR homozygosity was present in 8.9% of patients. Immunological risk (cPRA ≥84) and HLA-DR homozygosity were the strongest predictors of prolonged waiting time. Patients with both factors had only an 8% chance of transplantation, versus 84% in those with neither. The model showed 66.4% accuracy. Multivariate analysis revealed increased transplant probability among patients under 60 (HR 1.162), with diabetes (HR 1.166), and with blood types A, B, or AB compared to O. Lower immunological risk (HR 2.718) and the absence of HLA-DR homozygosity (HR 1.824) were favorable. The highest predicted transplant likelihood (HR 9.72) was for younger diabetic females with blood type AB, cPRA <84, and no HLA-DR homozygosity. No association was found between HLA-A alleles and transplant status. However, HLA-B44 was more frequent (p = 0.012) and HLA-DR8 less frequent (p < 0.001) among transplant recipients. 

This study highlights that high sensitization and HLA-DR homozygosity pose significant barriers to kidney transplantation in Brazil, restricting access and reinforcing existing disparities. In contrast, younger age, diabetes, and non-O blood types were associated with increased transplant probability. To address these challenges and promote greater equity, Brazil intends to update its national kidney allocation algorithm in the second half of 2025, incorporating sensitization status and HLA homozygosity into recipient prioritization. Current discussions also stress the importance of redefining regional boundaries, expanding interstate organ sharing, and integrating advanced immunological tools into the allocation framework. Proposed enhancements include broader HLA typing, with antibody screening across all 11 classical loci (HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1, -DPB1), and the adoption of virtual crossmatching to optimize compatibility assessment, reduce cold ischemia time, and improve transplant outcomes.