MECHANISMS OF HYPOALBUMINEMIA IN ENDSTAGE RENAL DISEASE

说明(改编自应用程序) 美国国立卫生研究院资助了一项为期多年的多中心研究，以建立 透析量(KT/V)与透析器通透性的关系 在多个中心研究的一组血液透析患者的结果 确定终末期肾病(ESRD)死亡率增加的原因 美国的病人--血液研究。而低蛋白血症是最严重的 ESRD死亡的强大预测因子，这些人低蛋白血症的原因 患者服用补充剂不会增加白蛋白水平和静脉注射氨基 酸只是部分且不一致的有益物质。相比之下，白蛋白 当患者进食时，合成和血清白蛋白迅速增加 在饥饿之后，这表明营养不良可能不是主要的 终末期肾病并发低蛋白血症1例。我们建议测试一种替代方案 假设，低白蛋白血症是由于白蛋白合成受到抑制所致 作为急性期反应的一部分，而不是由于营养不良。白蛋白 浓度与α2-巨球蛋白(α2-M)、C反应 蛋白(CRP)和血清淀粉样蛋白A(SAA)在终末期肾病患者中的变化及其预测意义 死亡比白蛋白浓度更好。白蛋白合成相关 与Alpha2 M呈负相关，而不是营养状况，进一步支持 假设。我们建议确定白蛋白的相对贡献 基线合成、分解代谢、重分布和外部白蛋白丢失 血液学研究患者的白蛋白水平 [125 1]白蛋白的模建。我们将测量白蛋白动态平衡 白蛋白水平处于最低四分位数和 三个参与中心的上三个四分位数。我们将确定 营养因素(饮食史、PCRn、 人体测量学)和急性期反应(SAA、CRP、 α2M、纤维蛋白原、IL-β和肿瘤坏死因子α)和白蛋白丢失 建立基线白蛋白水平和合成速率 回归模型。然后我们将确定营养方面的变化 白蛋白浓度测定变化前的状态或炎症 营养状况和急性期蛋白和细胞因子每月和损失 每两周一次透过透析膜的白蛋白。我们将重复动力学 白蛋白浓度改变为0.3g/dL后的白蛋白建模 或24个月后，如果白蛋白保持不变，以确定 白蛋白动态平衡导致白蛋白浓度的变化。我们 将进一步确定KT/V、透析器透过率和重复使用的效果 白蛋白、营养状况和急性期反应的变化。

DESCRIPTION (Adapted from the application) The NIH has funded a multi-year multi-center study to establish the relationship between dialysis dose delivered (KT/V), dialyzer permeability and outcome in a group of hemodialysis patients studied in several centers to identify causes of increased mortality in end stage renal disease (ESRD) patients in the US - the HEMO study. While hypoalbuminemia is the most powerful predictor of death in ESRD, the cause of hypoalbuminemia in these patients is supplements do not increase albumin levels and intravenous amino acids are only partially and inconsistently beneficial. In contrast albumin synthesis and serum albumin increase promptly when patients are fed following starvation, suggesting that malnutrition may not be the primary case of hypoalbuminemia in ESRD. We propose to test an alternative hypothesis, that hypoalbuminemia results from suppressed albumin synthesis as part of the acute phase response rather than from malnutrition. Albumin concentration correlates with alpha2 macroglobulin (alpha2 M), C reactive protein (CRP) and serum amyloid A (SAA) in ESRD patients, and CRP predicts death better than does albumin concentration. Albumin synthesis correlates negatively with alpha2 M and not nutritional status, further supporting the hypothesis. We propose to determine the relative contributions of albumin synthesis, catabolism, redistribution and external albumin loss on baseline albumin levels in patients participating in the HEMO study using kinetic modeling of [125 1] albumin. We will measure albumin homeostasis in an equal number of patients with albumin levels in the lowest quartile and in the upper 3 quartiles in 3 participating centers. We will determine the relative effect of nutritional factors (dietary history, PCRn, anthropometrics) and the acute phase response (measurement of SAA, CRP, alpha2M, fibrinogen, IL-Beta and TNF theta) and albumin losses in establishing baseline albumin levels and synthesis rate using multiple regression models. We will then establish whether changes in nutritional status or inflammation precede changes in albumin concentration measuring nutritional status and acute phase proteins and cytokines monthly and loss of albumin across dialysis membranes bi-weekly. We will repeat kinetic albumin modeling after either a change in albumin concentration of 0.3 g/dL or after 24 months if albumin remains unchanged to identify changes in albumin homeostasis responsible for changes in albumin concentration. We will further establish the effect of KT/V, dialyzer permeability and reuse on changes in albumin, nutritional status and acute phase response.