*Purpose: Our previous results showed that low immunogenicity (IM) donors improved kidney allograft survival in non-sensitized recipients. Herein, we examined how the level of peak pre-transplant panel reactive antibody (PRA=0-100%) may affect the beneficial impact of low HLA IM.

*Methods: The donor/recipient IM was evaluated by the hydrophobic mismatch score (HMS) calculated from the hydrophobic charges of donor/recipient polymorphic amino acids. The 78,865 donor/recipient cohort (SRTR) was converted from 2- to 4-digit HLA-A/B/DR and the HMS calculated by the Cambridge algorithm. The HMS IM on a scale of 0-20 was correlated between four PRA groups (0-49%; 50-79%; 80-94%; and 95-100%) with Kaplan-Meier survival estimates and Cox regression analyses.

*Results: Non-sensitized and weakly sensitized (PRA=0-49%) as well as mildly sensitized (PRA=50-79%) recipients showed an improved graft survival at different HMS thresholds, namely HMS=0, HMS≤3.0, and HMS≤7.8. In contrast, highly (PRA=79-97%) and very highly (HMS-98-100%) sensitized recipients had improved graft survivals only at HMS=0 and HMS≤3.0 but not at higher HMS thresholds (Fig. 1). The logistic regression analysis also demonstrated the impact of PRA on IM defined by the HMS thresholds when measured by the incidence of rejection. Lowering HMS threshold also compensated the impact of higher PRA values based on the number of early acute rejection episodes (Table 1). This HMS threshold had significant impact on graft survival at PRA 0-49% (p<0.001), while it became less significant at PRA 50-97% (p<0.05) and became non-significant at PRA 98-100% (p=NS).

*Conclusions: Low IM (confirmed by lower HMS thresholds) significantly improved graft survivals and reduced number of rejection episodes in sensitized patients. Thus, the negative PRA effect on graft outcomes may be improved by adjusting the HMS IM thresholds.

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