Increasing donor kidney age significantly aggravates the negative effect of pretransplant donor-specific anti-HLA antibodies on kidney graft survival

Michiel GH Betjes ^1* Judith A Kal-Van Gestel ¹ Dave Roelen ² Marcia Kho ¹ Sebastiaan Heidt ¹ Annelies De Weerd ¹ Jacqueline Van De Wetering ¹

• ¹ Erasmus Medical Center, Rotterdam, Netherlands
• ² Leiden University Medical Center (LUMC), Leiden, Netherlands

Background and hypothesis. The presence of donor-specific anti-HLA antibodies before kidney transplantation (preDSA) is associated with decreased graft survival. The hypothesis was investigated that increasing donor kidney age is negatively associated with the impact of preDSA on graft survival.Outcome of kidney transplantation in a single center cohort of 2024 patients transplanted between 2010 and 2020 with a follow-up of at least 3 years was analyzed to assess this relation.. DSA before transplantation were present in 14% of recipients The presence of DSA before transplantationand showed an independent association with graft loss. The preDSA against HLA class I (2%) or class II (7%) had an adjusted hazard ratio (HR) for death censored graft failure of 5.8 (95% CI 4.4-7.7), while the combination (5%) had a HR of 18.6 (95% CI 13.8-25.1). The preDSA associated increase in graft failure was caused primarily by an increase in the incidence of antibody-mediated rejection (ABMR), intragraft thrombosis and primary non-function. These effects were observed more frequently in the deceased donor kidney transplantations compared to living donor kidney transplantations. The incidence of ABMR was not associated with donor kidney age. However, increasing kidney donor donor kidney age significantly aggravated the negative effect of preDSA on graft survival. For instance, recipients of ≥65 years transplanted with a deceased donor kidney of ≥65 years had an uncensored 1-year and 3-year graft survival of 83% and 67% if transplanted without DSA, this decreased to 56% and 35% if transplanted in the presence of DSA. For comparison, recipients of ≥65 years of a deceased donor kidney of <65 years of age had an uncensored 1-year and 3-year graft survival of 92 % and 78% without preDSA, and if transplanted with preDSA this decreased to 77% and 69%.Conclusions. The negative effect of circulating DSA at time of transplantation on both early and late death-censored graft survival is heavily influenced by donor age.