Microcirculatory dysfunction and glucose homeostasis in peritoneal dialysis

Abstract

Abstract Compared with hospital based therapies, peritoneal dialysis (PD) offers many advantages to patients with end stage renal disease in terms of greater autonomy and independence in addition to its health economic benefits. Cardiovascular morbidity and mortality in dialysis cohorts remains well in excess of the general population. The majority of this excess risk is attributable to a high prevalence of traditional cardiovascular risk factors and the consequences of chronic uraemia. However dialysis patients are at significant risk for systemic microvascular dysfunction which may represent an important non-traditional risk factor for cardiovascular disease in this group. In this thesis I present evidence of impairment in multiple aspects of cutaneous microvascular reactivity in PD patients compared with healthy controls and patients with similar metabolic and cardiovascular risk profiles. This impairment appears to be the result of deficiencies in multiple vasodilatory pathways and is attributable to uraemia or an aspect of PD therapy and not to co-morbidities. During peritoneal dialysis the rate of peritoneal small solute transport is governed primarily by the peritoneal microcirculation. However in this study there was no relationship between rate of small solute transport and the degree of systemic microvascular dysfunction. Data from this study adds to the increasingly compelling evidence for intraperitoneal inflammation as the major determinant of small solute transport. It has been suggested that the process of PD itself may also contribute to the increased cardiovascular risk, specifically the systemic effects of peritoneally absorbed glucose. In this thesis continuous glucose monitors provide novel insight into the 72 glycaemic profiles of PD patients and patients with stage 5 chronic kidney disease who are not on dialysis. In this cohort there was no significant increase in average interstitial glucose levels or the degree of glycaemic variability in PD patients compared with their non-dialysis controls. Neither was there any strong relationship between dialysate glucose exposure and interstitial glucose levels. However distinctly different patterns of glycaemia were noted in patients receiving automated peritoneal dialysis compared with those receiving continuous ambulatory peritoneal dialysis which require further investigation.