HLA Matching in US Kidney Transplantation Over Three Decades: Trends, Disparities, and Clinical Implications

Human Leukocyte Antigen (HLA) matching is associated with better allograft survival and reduced immunosuppression requirements in kidney transplantation. However, the effects of evolving US kidney allocation policies and changes in living donor demographics on the degree of HLA matching over time have not been characterized.

Using Scientific Registry of Transplant Recipients data from 1991 to 2023, we evaluated temporal trends in zero HLA-ABDR and zero HLA-DR mismatches among living and deceased donor kidney transplants, including across racial and age subgroups. We further examined associations between HLA mismatching and graft outcomes across transplant eras (1990s, 2000s, 2010s) and peak calculated panel reactive antibody (CPRA) at repeat waitlisting.

The proportion of well-matched kidney transplants declined substantially over time. In 2023, 5% (1,145) and 16% (3,804) of transplants had zero HLA-ABDR and zero HLA-DR mismatches, respectively, compared with 11% (318) and 32% (929) in 1991. Trends in deceased donor transplantation were intermittent and temporally aligned with allocation policy changes, whereas declines in living donor transplantation were continuous and paralleled reductions in biologically related donors. These patterns were consistent across racial and age groups, with the lowest rates observed among children and racial minority deceased donor kidney recipients. Although the associations are weaker in recent eras, HLA matching remained significantly associated with better graft survival, and greater HLA mismatching was associated with significantly higher CPRA at repeat listing.

HLA matching in US kidney transplantation has declined markedly over the past three decades, with children and racial minorities currently experiencing the lowest levels of matching. Well-matched transplants experience better graft longevity, but the magnitude of benefit has diminished in the most recent era.