Hypoalbuminaemia, systemic albumin leak and endothelial dysfunction in peritoneal dialysis patients

Abstract

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 ¹²⁵I albumin [transcapillary escape rate of albumin (TER_alb)]. 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 TER_alb 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 TER_alb. Cluster 2 was non-inflamed, preserved muscle mass and more normal TER_alb. Cluster 3 had highest TER_alb, 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. TER_alb 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.