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HLA MISMATCHES VS. EPLET MISMATCHES IN KIDNEY TRANSPLANTATION

Introduction: In Russia, each transplant center has its own separated waiting list. This significantly reduces the ability to select the optimal recipient in terms of tissue compatibility. Objective: to perform a multivariate analysis of the effect of the number of epitope mismatches on transplant survival. Materials and Methods: An observational retrospective cohort study was performed, which included 824 adult recipients. All patients underwent transplantation of a cadaveric kidney compatible by blood group. The endpoint was considered transplant loss. The death-censored graft survival was evaluated. The calculation of the number of epitope mismatches (EpMM) was carried out using information from publicly available resources about the population frequency of haplotypes and the repertoire of epitopes with confirmed immunogenicity. All possible combinations of the donor and recipient genotypes were compiled, and the probability of each combination was calculated. Then, for each combination with nonzero probability the number of donor epitopes absent in the recipient was determined. After that, the weighted average EpMM was calculated, where the weighted coefficient was the normalized probability of occurrence of each combination. Results: All recipient donor pairs had HLA incompatibilities (HLA MM): 1.9% 1 HLA MM, 6.7% 2 HLA MM, 29.9% 3 HLA MM, 38.5% 4 HLA MM, 18, 1% 5 HLA MM, 4.9% 6 HLA MM. EpMM increased with increase of the HLA MM count, but not linearly: 6 [interquartile range of RBI 4; 7] (from 2 to 7), 12 [IQR 7.74; 17.25] (from 4 to 20), 18 [IQR 14; 22] (from 8 to 28), 24 [IQR 20; 30] (from 10 to 33), 30.5 [IQR 25; 37] (from 13 to 35) and 36 [IQR 26.5; 44.5] (from 15 to 40) for 1, 2, 3, 4, 5, and 6 HLA MM, respectively. Significant risk factors for graft loss in the adjusted multivariate model were: HLA MM p <0.001; duration of conservation HR 1.08 for hour [95% CI 1.02; 1.16], p = 0.01; panel-reactive antibodies (PRA) HR 1.24 for every 10% [95% CI 1.06; 1.58], p = 0.017; but not the type of donor, age and gender of the recipient. (Fig. 1)