Session Time: 3:15pm-4:45pm
Presentation Time: 3:27pm-3:39pm
*Purpose: A severe shortage of deceased donor kidneys limits access to kidney transplantation. Limited longterm graft function exacerbates this shortage as 12% of the waiting list is for re-transplantation. Currently, median kidney graft survival is only 10 years for deceased donors and 12 years for live donors. We propose to improve graft survival outcomes by lowering immunogenicity based on HLA physiochemical properties.
*Methods: We calculated the hydrophobic mismatch score (HMS) of HLA-A/B/DR as the sum of hydrophobic charges only for HLA polymorphic amino acids different between a donor and a recipient (by Cambridge algorithm). The 2-digit HLA-A/B/DR of 78,000 actual deceased donor/recipient pairs (obtained from the SRTR; 2000-2016) were first imputed into 4-digit and then HMS values calculated.
*Results: The multiple Cox regression showed that HMS values were associated with the graft survival and selected covariates. In Kaplan-Meier analyses, the best-matched transplants (HMS=0) had an excellent median graft survival of 18.1 years. The well-matched pairs with an HMS≤3.0 (n=11,483) had equally impressive graft survival of 16.1 years, almost identical to 16.2 years in patients with 0-HLA/1-HLA mismatch combined (n=6,724). The median HMS≤7.8 threshold still produced very good graft survival of 14.3 years. Our computer simulation estimated that 75% of 1,000 and 88% of 10,000 donor/recipient pairs with an HMS>3.0 could be re-matched into pairs with HMS≤3.0 whereas 100% of 1000 or 10,000 pairs with HMS>7.8 could be re-matched into HMS≤7.8.
*Conclusions: We propose that HMS-based selection of low immunogenicity donors will avoid high immunogenicity transplants and will increase the average kidney graft survival to over 16 years. If the average deceased donor graft survival of 16,000 deceased donor kidney recipients could be increased from 10 years to 16 years, this would provide nearly 1 million additional years of graft survival over ten years and significantly reduce the waiting time for all.
To cite this abstract in AMA style:Bekbolsynov D, Mierzejewska B, Borucka J, Khuder SA, Rees M, Green R, Stanislaw S. Low Physiochemical Immunogenicity Scores Improve Long-Term Survival of Deceased Donor Kidney Transplants [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/low-physiochemical-immunogenicity-scores-improve-long-term-survival-of-deceased-donor-kidney-transplants/. Accessed September 24, 2020.
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