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

BACKGROUND: 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. METHODS: This was a cross-sectional study of 41 prevalent PD patients. Endothelial barrier function was measured as transcapillary escape rate of (125)I 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. RESULTS: 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. CONCLUSIONS: 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.

Achieving euvolemia in peritoneal dialysis patients: a surprisingly difficult proposition.

Preservation of residual renal function and reduced early mortality rates are likely to reflect the relative ease with which euvolemia can be achieved in peritoneal dialysis (PD) patients. Yet, there is concern that these patients are frequently fluid loaded, fuelled by the problems of ultrafiltration failure and worse survival observed in anuric patients with low fluid removal. In reality, the proportion of PD patients that are overhydrated is not dissimilar to hemodialysis but the challenges in achieving euvolemia might be different. These include (i) the undesirability of driving down the dry weight, in part to avoid excess glucose exposure, in part because there is a trade off in preserving residual renal function, (ii) limitations in our knowledge of how best to measure and apply measurements of fluid status in clinical practice, (iii) limitations imposed by the therapy itself (e.g., membrane function, sodium sieving), and (iv) the influence of hypoalbuminemia on fluid distribution. Treatment options that enable improved fluid management are available (e.g., automated peritoneal dialysis and icodextrin for rapid transporters, dietary salt restriction) or on the horizon (e.g., low sodium dialysates). We now need studies that aid clinicians in their decision making to enable best fluid management in their patients.