Yu, Zanzhe (2013) Local and systemic endothelial injury in renal failure treated with peritoneal dialysis. Doctoral thesis, Keele University.

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Abstract

Excess fluid and waste products of metabolism, as well as protein, are removed from the peritoneal cavity in Peritoneal Dialysis (PD). Increased peritoneal protein clearance (Pcl) is associated with a greater risk of mortality. It is not clear whether this association reflects systemic endothelial injury or local peritoneal capillary damage and inflammation, or both. To investigate this problem a series of analyses were undertaken in different incident, prevalent and longitudinal patient cohorts. Transcapillary escape rate of albumin (TERalb) was measured to determine systemic capillary permeability. Luminex assays combined with principle component analysis were applied to measure endothelial biomarker patterns.

It was demonstrated that: (1) Pcl is a function of both local peritoneal inflammation, membrane area (PSTR) and comorbidity (especially cardiovascular) but only its association with the latter predicted survival. (2) There is a progressive uncoupling of the Pcl, (indicative of large pore pathway) and PSTR (effectively the small pore area) with time on PD. (3) Isolated small pore ultrafiltration (due to icodextrin) decreases with prolonged time on PD and is also uncoupled from the increase in peritoneal membrane area. (4) The systemic endothelial barrier function is decreased in PD patients, especially diabetics, but not associated with hypoalbuminaemia which is linked to systemic inflammation. (5) Hydration status is related to plasma albumin concentration but not endothelial dysfunction as measured by soluble biomarkers.

Pcl is a function of both local peritoneal factors, e.g. inflammation and progressive fibrosis, and systemic patient characteristics, e.g. age and comorbidity. The influence of comorbidity is complex depending on type, associated patterns of endothelial injury and causes of associated hypoalbuminaemia. The importance of plasma colloidal pressure in determining fluid status was emphasized. Strategies to improve fluid distribution should focus on reducing peritoneal protein loss and increasing albumin synthesis rather than blocking systemic vascular leak.

Item Type: Thesis (Doctoral)
Subjects: R Medicine > R Medicine (General)
Divisions: Faculty of Medicine and Health Sciences > Institute for Science and Technology in Medicine
Depositing User: Michael Debenham
Date Deposited: 09 Jun 2016 16:35
Last Modified: 09 Jun 2016 16:35
URI: http://eprints.keele.ac.uk/id/eprint/1828

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