Department of Clinical Immunology 7631, University Hospital of Copenhagen - Rigshospitalet, Copenhagen, Denmark.
Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
Scand J Immunol. 2023 Jan;97(1):e13225. doi: 10.1111/sji.13225. Epub 2022 Nov 8.
Long-term allograft survival remains a challenge in kidney transplantation. In this study, we aimed to identify biomarkers for potentially modifiable pathways involved in the outcome of kidney transplantation. We tested the hypothesis that a pre-existing systemic environment with endothelial cell activation in the recipient is associated with the outcome after kidney transplantation. In a retrospective study cohort of 611 kidney transplanted patients, we investigated associations between serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) before transplantation and delayed graft function, acute rejection, graft loss and mortality after transplantation. We adjusted associations for age, sex, preformed donor-specific antibodies (DSA), pretransplant diabetes, cardiovascular disease and dialysis. Additionally, we investigated if associations between endothelial cell activation markers and outcomes differed in recipients with and without preformed DSA. Serum levels of endothelial cell activation markers were associated with delayed graft function and mortality but not with rejection. Additionally, high levels of sICAM-1 were associated with graft loss. Associations were most pronounced in recipients without DSA, adjusted for potential confounders. Data suggest that endothelial cell activation at the time of transplantation is associated with graft loss and mortality after kidney transplantation, especially in transplant candidates without preformed DSA.
在肾移植中，长期移植物存活仍然是一个挑战。在这项研究中，我们旨在确定与肾移植结果相关的潜在可调节途径的生物标志物。我们假设受者体内预先存在的内皮细胞激活的全身环境与肾移植后的结果有关。在一项回顾性研究队列中，我们研究了 611 例接受肾移植的患者在移植前血清可溶性细胞间黏附分子-1（sICAM-1）和可溶性血管细胞黏附分子-1（sVCAM-1）水平与移植后延迟移植物功能、急性排斥反应、移植物丢失和死亡率之间的关系。我们调整了年龄、性别、预先形成的供体特异性抗体（DSA）、移植前糖尿病、心血管疾病和透析等因素的相关性。此外，我们还研究了内皮细胞激活标志物与有和没有预先形成的 DSA 的受者之间的相关性是否存在差异。内皮细胞激活标志物的血清水平与延迟移植物功能和死亡率相关，但与排斥反应无关。此外，高水平的 sICAM-1 与移植物丢失相关。在调整了潜在混杂因素后，这些相关性在没有 DSA 的受者中最为明显。数据表明，移植时的内皮细胞激活与肾移植后移植物丢失和死亡率相关，尤其是在没有预先形成的 DSA 的移植候选者中。
