MONOCYTE PHENOTYPES AND MORBIDITY IN UREMIA

在许多体外观察到的白细胞功能异常中 从肾功能衰竭患者中分离出来的单核细胞功能障碍 最大的能力来预测临床上重要的传染病事件 活着。这些单核细胞功能异常中的许多类似于 观察时营养不足。因为有了某些透析 膜导致单核细胞衍生细胞因子的异常释放 它们对中间代谢有分解代谢的作用，它一直是 提示透析本身可能会刺激发展 营养不良。因此，我们认为，细胞的功能表型 单核细胞是感染性和营养性的关键决定因素 透析患者的发病率。我们认为其表型为 与这种过度风险相关的单核细胞在体外可以被定义为 会为处于危险中的病人提供一个发病前的标记。此外， 定义这样的表型将允许体外分析 单核细胞导向的调节性细胞因子纠正高血压的能力 功能异常。根据这些目标，我们提出了一个前瞻性的， 患者在由以下成分组成的膜上进行透析的交叉研究 铜丙烷、醋酸纤维素酯、聚丙烯腈和聚砜。 将在六个月内分离单核细胞进行表型分析。 每个膜上的透析量；单核细胞表型将基于 细胞程序性死亡的动力学及其精细选择的能力 营养相关细胞因子、促炎性脂类与反应性 氧物种，介导细胞毒性，并作为抗原发挥作用 呈现细胞。异常的单核细胞表型将是相关的 患者结局，由感染并发症定义，包括 尿素营养参数动力学模型，精选血浆水平 蛋白质、体内免疫学评估和饮食历史。

Of the numerous in vitro functional abnormalities observed for leukocytes isolated from patients with renal failure, monocyte dysfunction has the greatest capacity to predict a clinically significant infectious event in vivo. Many of these monocyte functional abnormalities resemble those observed with inadequate nutrition. Because dialysis with certain membranes results in the abnormal release of monocyte-derived cytokines which have a catabolic effect on intermediary metabolism, it has been suggested that dialysis per se may be provocative for the development of malnutrition. Therefore, we suggest that the functional phenotype of the monocyte is a critical determinant of infectious and nutritional morbidity in dialysis patients. We propose that the phenotype of monocyte associated with this excessive risk can be defined in vitro and will provide a premorbid marker of the patient at risk. Further, defining such a phenotype will permit an in vitro analysis of the capacity of monocyte-directed regulatory cytokines to correct the abnormal function. Pursuant to these aims, we propose a prospective, cross-over study in which patients are dialyzed on membranes composed of cuprophane, cellulose acetate, polyacrylonitrile, and polysulfone. Monocytes will be isolated for phenotypic analysis during the six months of dialysis on each membrane; monocyte phenotyping will be based upon the kinetics of programmed cell death, and their capacity to elaborate select nutritionally relevant cytokines, proinflammatory lipids and reactive oxygen species, to mediate cytotoxicity, and to function as antigen presenting cells. The abnormal monocyte phenotypes will be correlated with patient outcome, defined by infectious complications and inclusive nutritional parameters of urea kinetic modelling, plasma levels of select proteins, in vivo immunologic assessment, and dietary history.