Abstract
We evaluated the impact of human leukocyte antigen (HLA) disparity (immunogenicity; IM) on long-term kidney allograft survival. The IM was quantified based on physicochemical properties of the polymorphic linear donor/recipient HLA amino acids (the Cambridge algorithm) as a hydrophobic, electrostatic, amino acid mismatch scores (HMS\\AMS\\EMS) or eplet mismatch (EpMM) load. High-resolution HLA-A/B/DRB1/DQB1 types were imputed to calculate HMS for primary/re-transplant recipients of deceased donor transplants. The multiple Cox regression showed the association of HMS with graft survival and other confounders. The HMS integer 0–10 scale showed the most survival benefit between HMS 0 and 3. The Kaplan–Meier analysis showed that: the HMS=0 group had 18.1-year median graft survival, a 5-year benefit over HMS>0 group; HMS ≤ 3.0 had 16.7-year graft survival, a 3.8-year better than HMS>3.0 group; and, HMS ≤ 7.8 had 14.3-year grafts survival, a 1.8-year improvement over HMS>7.8 group. Stratification based on EMS, AMS or EpMM produced similar results. Additionally, the importance of HLA-DR with/without -DQ IM for graft survival was shown. In our simulation of 1,000 random donor/recipient pairs, 75% with HMS>3.0 were re-matched into HMS ≤ 3.0 and the remaining 25% into HMS≥7.8: after re-matching, the 13.5 years graft survival would increase to 16.3 years. This approach matches donors to recipients with low/medium IM donors thus preventing transplants with high IM donors.
Highlights
The impact of the human leukocyte antigen (HLA)-A/B/DR mismatch (MM) on kidney allograft survival has been a subject of extensive research [1,2,3,4]
We propose that a continuous IM scale offers greater freedom in finding weakly immunogenic transplants, allowing improvement of kidney allograft survival
Out of all 132,515 recipients of deceased donors, high-resolution HLAs were imputed for 78,864 donor/recipient pairs based on available race and HLA-A/B/DR 2-digit antigens; this cohort included 29,852 pairs with HLA-A/B/DRB1/DQB1 types available
Summary
The impact of the human leukocyte antigen (HLA)-A/B/DR mismatch (MM) on kidney allograft survival has been a subject of extensive research [1,2,3,4]. In the U.S, most of ABO-compatible kidney transplants are performed without HLA matching, with the exception for few special programs [5, 9, 10]. Between 2012 and 2016, only 16.4% of patients received “well-matched” deceased donor kidney transplants at 0-, 1- or 2-HLA MM. The remaining 83.6% of kidney transplants had 3-, 4-, 5-, and 6-HLA MM and should be considered as poorly matched [11]. Existing government programs prioritize 0-HLA MM kidney transplants for sensitized patients [12]. The remaining procured kidneys are allocated according to UNOS policies that rarely grant points for HLA matches. It is logistically impossible to match HLA for every transplant, and less than 10% of patients receive 0-HLA MM kidney transplants every year [13]
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