Betjes Michiel G H, Kal-van Gestel Judith A, Roelen Dave, Kho Marcia M L, Heidt Sebastian, de Weerd Annelies E, van de Wetering Jacqueline
Department of Internal Medicine, Erasmus Medical Center Transplant Institute, University Medical Center, Rotterdam, Netherlands.
Department of Immunology, Leiden University Medical Center, Leiden, Netherlands.
Front Immunol. 2025 Apr 16;16:1574324. doi: 10.3389/fimmu.2025.1574324. eCollection 2025.
The presence of donor-specific anti-HLA antibodies before kidney transplantation (preDSAs) is associated with decreased graft survival. The hypothesis that increasing donor kidney age is negatively associated with the impact of preDSA on graft survival was investigated.
Outcome of kidney transplantation in a single center cohort of 2,024 patients transplanted between 2010 and 2020 with a follow-up of at least 3 years was analyzed to assess this relation.
DSAs before transplantation were present in 14% of recipients and 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 an 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 donor kidney age significantly aggravated the negative effect of preDSA on graft survival. For instance, recipients aged ≥65 years transplanted with a deceased donor kidney aged ≥65 years had an uncensored 1- and 3-year graft survival of 83% and 67%, respectively, if transplanted without DSA. This decreased to 56% and 35% if transplanted in the presence of DSA. For comparison, recipients aged ≥65 years of a deceased donor kidney aged <65 years had an uncensored 1- and 3-year graft survival of 92% and 78%, respectively, without preDSA, and if transplanted with preDSA, this decreased to 77% and 69%, respectively.
The negative effect of circulating DSA at the time of transplantation on both early and late death-censored graft survival is heavily influenced by donor age.
肾移植前供者特异性抗人白细胞抗原（HLA）抗体（preDSA）的存在与移植肾存活期缩短相关。本研究探讨了供肾年龄增加与preDSA对移植肾存活影响呈负相关这一假设。
分析了2010年至2020年间在单中心接受肾移植的2024例患者的队列研究结果，随访时间至少3年，以评估这种关系。
14%的受者移植前存在DSA，且与移植肾丢失独立相关。针对HLAⅠ类（2%）或Ⅱ类（7%）的preDSA导致死亡截尾移植肾失功的校正风险比（HR）为5.8（95%置信区间[CI] 4.4 - 7.7），而两者合并存在时（5%）HR为18.6（95% CI 13.8 - 25.1）。preDSA相关的移植肾失功增加主要是由于抗体介导的排斥反应（ABMR）、移植肾内血栓形成和原发性无功能的发生率增加所致。与活体供肾移植相比，这些影响在尸体供肾移植中更常见。ABMR的发生率与供肾年龄无关。然而，供肾年龄增加显著加重了preDSA对移植肾存活的负面影响。例如，接受年龄≥65岁尸体供肾移植且年龄≥65岁的受者，若移植时无DSA，其1年和3年未截尾移植肾存活率分别为83%和67%。若移植时有DSA，这一比例分别降至56%和35%。相比之下，接受年龄<65岁尸体供肾移植且年龄≥65岁的受者，若无preDSA，其1年和3年未截尾移植肾存活率分别为92%和78%，若移植时有preDSA，这一比例分别降至77%和69%。
移植时循环DSA对早期和晚期死亡截尾移植肾存活的负面影响受供者年龄的严重影响。
