Exploring the effects of expanded solute removal in haemodialysis

Background: Patients on dialysis treatment have a significantly increased risk of cardiovascular disease. Inflammation and cardiovascular disease, characterised by endothelial dysfunction, are intimately linked in this patient group. Medium Cut-Off (MCO) Haemodialysis (HDx) provides improved clearance of larger middle molecules (up to 45kda) compared with high-flux haemodialysis. Expanded solute removal, through HDx could be biologically significant in modifying endothelial function and cardiovascular risk. This thesis focuses on research investigating the effects of HDx treatment on markers of endothelial health, inflammation and patient-reported outcome measures. Methods: 64 patients on haemodiafiltration (HDF) treatment were recruited and randomised in a prospective open-label randomised controlled trial (RCT) with patients either continuing on HDF or switching to HDx. Outcome measures included changes in a large panel of biomarkers including EMV, inflammatory cytokines and larger middle molecules. Body composition monitoring, patient-reported outcome measures (POS-S-Renal, Chalder Fatigue Score, Dialysis Recovery Time) and pulse wave velocity were also measured. Cell culture experiments were carried out in a subset of patients. Results: There was no difference in plasma EMV concentration between the two groups at 24 weeks. HDx was non-inferior to high volume HDF with respect to most clinical and biological markers and in vitro endothelial cell function. There was a signal that HDx treatment could be associated with a greater preservation of lean tissue index compared with HDF. HDx may be associated with an improvement in self-reported dialysis recovery time. Conclusion: HDx therapy appears to be non-inferior to HDF therapy and may be associated with optimisation of nutritional status and improvements in patientreported outcome measures. Mechanisms behind the study findings require further exploration. In an era where equipoise still exists between diffusive and convective treatment modalities, HDx, where performance is maintained at modest blood flow rates and without the need for infusion of high volumes of substitution fluid, could be an important future direction.