Division of Nephrology and Hypertension, University of California, Orange, California, USA.
J Ren Nutr. 2012 Jan;22(1):149-56. doi: 10.1053/j.jrn.2011.10.020.
End-stage renal disease (ESRD) is simultaneously associated with immune activation, marked by systemic inflammation, and immune deficiency. Systemic inflammation contributes to atherosclerosis, cardiovascular disease, cachexia, and anemia, whereas immune deficiency leads to impaired response to vaccination, and increased incidence and severity of microbial infections. ESRD-associated inflammation and immune deficiency are associated with the following: (a) general expansion of monocytes and elevations of their basal integrin, Toll-like receptor (TLR)-2, TLR-4 expression, cytokine production, and reactive oxygen species (ROS) generation and reduced phagocytic capacity, (b) depletion and impaired inhibitory activity of regulatory T cells, (c) spontaneous activation, degranulation, increased basal ROS production, decreased phagocytic capacity, and increased apoptosis of the circulating polymorphonuclear leukocytes, (d) upregulation of ROS production machinery and chemokine expression in the cellular constituents of various tissues, highlighting participation of nonimmune cells in the prevailing inflammatory state, (e) depletion of the antigen-presenting dendritic cells, (f) reduced CD4/CD8 T cell ratio and depletion of naïve and central memory T cells, (g) diffuse B cell lymphopenia leading to impaired humoral immunity, and (h) increased proinflammatory activity of low-density lipoprotein and reduced anti-inflammatory capacity of high-density lipoprotein. Thus, ESRD-associated inflammation is due to activation of innate immune system, orchestrated by monocytes, macrophages, granulocytes, and cellular constituents of other organs/tissues. This is coupled with immune deficiency that is caused by depletion of dendritic cells, naïve and central memory T cells and B cells, and impaired phagocytic function of polymorphonuclear leukocytes and monocytes.
终末期肾病（ESRD）同时伴有免疫激活，表现为全身炎症和免疫缺陷。全身炎症导致动脉粥样硬化、心血管疾病、恶病质和贫血，而免疫缺陷导致疫苗反应受损，以及微生物感染的发生率和严重程度增加。ESRD 相关的炎症和免疫缺陷与以下因素有关：（a）单核细胞普遍扩张，其基础整合素、Toll 样受体（TLR）-2、TLR-4 表达、细胞因子产生和活性氧（ROS）生成升高，吞噬能力降低，（b）调节性 T 细胞耗竭和功能障碍，（c）循环多形核白细胞自发激活、脱颗粒、基础 ROS 产生增加、吞噬能力降低和凋亡增加，（d）各组织细胞成分中 ROS 产生机制和趋化因子表达上调，突出非免疫细胞参与流行的炎症状态，（e）抗原呈递树突状细胞耗竭，（f）CD4/CD8 T 细胞比值降低和幼稚及中央记忆 T 细胞耗竭，（g）弥漫性 B 细胞淋巴细胞减少导致体液免疫受损，以及（h）低密度脂蛋白的促炎活性增加和高密度脂蛋白的抗炎能力降低。因此，ESRD 相关的炎症是由于先天免疫系统的激活，由单核细胞、巨噬细胞、粒细胞和其他器官/组织的细胞成分协调。这与树突状细胞、幼稚和中央记忆 T 细胞和 B 细胞耗竭以及多形核白细胞和单核细胞吞噬功能受损导致的免疫缺陷有关。
