Patients with end-stage renal disease (ESRD) exhibit a premature aging phenotype of the immune system. Nevertheless, the etiology and impact of these changes in ESRD patients remain unknown. Compared to healthy individuals, ESRD patients exhibit accelerated immunosenescence in both T cell and monocyte compartments, characterized by a dramatic reduction in naïve CD4+ and CD8+ T cell numbers but increase in CD8+ TEMRA cell and proinflammatory monocyte numbers. Notably, within ESRD patients, aging-related immune changes positively correlated not only with increasing age but also with longer dialysis vintage. In multivariable-adjusted logistic regression models, the combination of high terminally differentiated CD8+ T cell level and high intermediate monocyte level, as a composite predictive immunophenotype, was independently associated with prevalent coronary artery disease as well as cardiovascular disease, after adjustment for age, sex, systemic inflammation and presence of diabetes. Levels of terminally differentiated CD8+ T cells also positively correlated with the level of uremic toxin p-cresyl sulfate. Aging-associated adaptive and innate immune changes are aggravated in ESRD and are associated with cardiovascular diseases. For the first time, our study demonstrates the potential link between immunosenescence in ESRD and duration of exposure to the uremic milieu.

中文翻译：

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终末期肾病中 T 淋巴细胞和单核细胞衰老相关变化加重的综合表征：iESRD 研究

终末期肾病 (ESRD) 患者表现出免疫系统过早衰老表型。然而，这些变化对 ESRD 患者的病因和影响仍然未知。与健康个体相比，ESRD 患者在 T 细胞和单核细胞区室中都表现出加速的免疫衰老，其特征是幼稚 CD4+ 和 CD8+ T 细胞数量显着减少，但 CD8+ TEMRA 细胞和促炎单核细胞数量增加。值得注意的是，在 ESRD 患者中，与衰老相关的免疫变化不仅与年龄增加呈正相关，而且与透析时间的延长呈正相关。在多变量调整逻辑回归模型中，高终末分化 CD8+ T 细胞水平和高中间单核细胞水平的组合，作为复合预测免疫表型，在调整了年龄、性别、全身炎症和糖尿病的存在后，与流行的冠状动脉疾病和心血管疾病独立相关。终末分化的 CD8+ T 细胞水平也与尿毒症毒素对甲酚硫酸盐的水平呈正相关。衰老相关的适应性和先天性免疫变化在 ESRD 中加重，并与心血管疾病有关。我们的研究首次证明了 ESRD 中的免疫衰老与暴露于尿毒症环境的持续时间之间的潜在联系。衰老相关的适应性和先天性免疫变化在 ESRD 中加重，并与心血管疾病有关。我们的研究首次证明了 ESRD 中的免疫衰老与暴露于尿毒症环境的持续时间之间的潜在联系。衰老相关的适应性和先天性免疫变化在 ESRD 中加重，并与心血管疾病有关。我们的研究首次证明了 ESRD 中的免疫衰老与暴露于尿毒症环境的持续时间之间的潜在联系。