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Effect of HLA matching on renal transplant survival
Insights
Human Leukocyte Antigen (HLA) matching significantly impacts kidney transplant success. Optimal HLA matching improves graft survival rates, reducing rejection episodes and enhancing long-term outcomes for recipients.
Area of Science:
- Immunogenetics
- Transplantation immunology
- Nephrology
Background:
- Human Leukocyte Antigen (HLA) compatibility is crucial for allograft survival.
- Cadaveric renal transplantation outcomes are influenced by the degree of HLA matching.
- Previous studies indicated HLA matching's importance, but large-scale data on its impact on graft survival and rejection is continuously analyzed.
Purpose of the Study:
- To evaluate the impact of HLA matching on cadaveric renal allograft survival.
- To assess the relationship between HLA mismatch levels and graft rejection episodes.
- To analyze the influence of HLA matching on transplant outcomes across different transplant centers.
Main Methods:
- Analysis of 30,139 first cadaveric renal transplants.
- Comparison of graft survival rates based on the number of HLA antigen mismatches.
- Correlation of HLA mismatch with early graft rejection incidence.
- Evaluation of center-specific practices regarding HLA matching and their impact on outcomes.
Main Results:
- Significant positive correlation between HLA matching and graft survival; a 32% difference at 10 years between best and worst matches.
- Zero HLA mismatches yielded superior graft survival (89% at 1 year, 83% at 3 years); survival declined stepwise with increasing mismatches.
- Reduced early rejection episodes in zero-mismatch recipients (12%) compared to highly mismatched (26%).
- HLA-DR mismatches affected short-term outcomes, while HLA-B mismatches influenced long-term graft survival.
Conclusions:
- HLA matching is a critical determinant of cadaveric renal allograft survival and rejection rates.
- The national sharing program has increased HLA-matched transplants, underscoring the clinical significance of precise matching.
- Optimizing HLA matching, particularly for HLA-DR and HLA-B loci, is essential for improving long-term kidney transplant success.
Abstract:
1. HLA matching had a significant impact on cadaveric renal allograft survival. The difference in graft survival rates between the best- and worst-matched recipients among the 30,139 first cadaver transplants was 11% at one year, 19% at 3 years, and a projected 32% at 10 years posttransplant (p < 001). 2. Kidneys with no HLA antigens mismatched to the recipient yielded a superior result compared with any other match level. The one- and 3-year graft survival rates were 89% and 83% at one and 3 years, respectively. Even a single HLA antigen mismatch resulted in substantially poorer survival rates of 84% and 72% at one and 3 years (p < 0.001, each comparison). Nevertheless, there was a stepwise decline in graft survival with increasing numbers of mismatched HLA antigens. 3. The number of HLA-matched first cadaver transplants performed has increased from 2% of the total in 1987 to 6% in 1992, as a result of the national 6-antigen-match sharing program instituted by UNOS in 1987 and expanded to include phenotypically matched kidneys in 1990. 4. The incidence of early graft rejection episodes correlated with the number of HLA antigens mismatched. Only 12% of the zero-mismatched recipients experienced early rejection, whereas 26% of those with 5 or 6 antigens mismatched had rejection episodes during the transplant hospitalization (p < 0.01). 5. Transplants performed at the top 20 United States centers (based upon multivariate ranking) showed a strong effect of HLA matching, especially with respect to long-term outcome. The survival difference between the best- and worst-match groups was 9% at one year, 16% at 3 years, and a projected 25% at 10 years (p < 0.05). 6. Similarly, the survival difference between the best- and worst-matched groups at the bottom 20 centers was 16% at one year, 22% at 3 years, and a projected 36% at 10 years (p < 0.01). The bottom 20 centers apparently placed more emphasis on matching. Transplants with fewer than 3 mismatched antigens accounted for 34% of first cadaver transplants in the bottom 20, compared with 26% at the top 20 centers. 7. When all 27 possible HLA-A,B,DR mismatch combinations were examined, those involving HLA-DR mismatches had a strong influence on graft outcome at 3 months, whereas those involving HLA-B mismatches had the most influence on long-term outcome. HLA-A-locus mismatches had the smallest effect on graft outcome.(ABSTRACT TRUNCATED AT 400 WORDS)