Hypoalbuminaemia, systemic albumin leak and endothelial dysfunction in peritoneal dialysis patients
Hypoalbuminaemia, systemic albumin leak and endothelial dysfunction in peritoneal dialysis patients
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DOI：
10.1093/ndt/gfs075
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发表时间：
2012-12-01
影响因子：
6.1
通讯作者：
Davies, Simon J.
中科院分区：
文献类型：
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作者：
Yu, Zanzhe;Tan, Boon Kay;Davies, Simon J.
炎症、低白蛋白血症和腹膜蛋白清除率是腹膜透析（PD）患者生存的重要预测因素。我们假设共同的联系是异常的内皮屏障功能。为了验证这一点，我们探讨了低白蛋白血症，全身白蛋白渗漏和可溶性标志物的全身炎症和内皮损伤之间的关联。内皮屏障功能测定为I-125白蛋白的跨毛细血管逃逸率[白蛋白的跨毛细血管逃逸率（TERalb）]。测定了17种血浆生物标志物，包括促炎细胞因子、内皮生物标志物和金属蛋白酶。用系统聚类分析（HCA）和主成分分析（PCA）对这一假说进行了探讨，结果表明：尿毒症患者的TERAb平均值为13.7 ± 8.9（/h），高于非尿毒症患者的8.22 ± 5.8（/h）。根据HCA的生物标志物模式，定义了三个患者群。聚类1的特征在于炎症、低白蛋白血症、过度水合和中间TERAlb。第2组为非炎症，保留肌肉质量和更正常的TERAlb。聚类3具有最高的TERAlb、血小板活化、保留的血浆白蛋白和中等高敏C反应蛋白水平。从生物标志物基质中鉴定出两个主成分（PC），PC 1，表明血小板活化，PC 2，促炎。TERAb与PC 1呈正相关，与PC 2无相关性。糖尿病和缺血性心脏病分别与PC 1和PC2.This探索性分析表明，内皮屏障功能降低PD患者，并与糖尿病状态和血小板活化标志物比炎症。相比之下，低白蛋白血症与炎症和动脉粥样硬化疾病的相关性更高，表明全身性内皮屏障功能、炎症和低白蛋白血症之间的关系更复杂，需要进一步验证。
Inflammation, hypoalbuminaemia and peritoneal protein clearance are important predictors of survival in patients treated with peritoneal dialysis (PD). We hypothesized that the common link is abnormal endothelial barrier function. To test this, we explored associations between hypoalbuminaemia, systemic albumin leak and soluble markers of systemic inflammation and endothelial injury.This was a cross-sectional study of 41 prevalent PD patients. Endothelial barrier function was measured as transcapillary escape rate of I-125 albumin [transcapillary escape rate of albumin (TERalb)]. Seventeen plasma biomarkers including pro-inflammatory cytokines, endothelial biomarkers and metalloproteinases were measured. Hierarchical clustering analysis (HCA) and principal component analysis (PCA) were used to explore the hypothesis.The mean TERalb was 13.7 8.9 (/h), higher than in non-uraemic subjects 8.22 5.8 (/h). Three patient clusters were defined from HCA according to their biomarker patterns. Cluster 1 was characterized by inflammation, hypoalbuminaemia, overhydration and intermediate TERalb. Cluster 2 was non-inflamed, preserved muscle mass and more normal TERalb. Cluster 3 had highest TERalb, platelet activation, preserved plasma albumin and intermediate high-sensitivity C-reactive protein levels. Two principal components (PCs) were identified from the biomarker matrix, PC1, indicating platelet activation and PC2, pro-inflammatory. TERalb was positively related to PC1 but not PC2. Diabetes and ischaemic heart disease were associated with PC1 and PC2, respectively.This exploratory analysis indicates that endothelial barrier function is decreased in PD patients and is associated with diabetic status and markers of platelet activation more than inflammation. In contrast, hypoalbuminaemia is associated more with inflammation and atherosclerotic disease indicating a more complex relationship between systemic endothelial barrier function, inflammation and hypoalbuminaemia which requires further validation.