Comparison of MCO HD on Markers of Vascular Health Compared With On-Line Haemodiafiltration (MoDal)

A Randomised Study Investigating the Effect of Medium Cut-Off Haemodialysis On Markers of Vascular Health Compared With On-Line HDF

The aim of this study is to evaluate haemodialysis treatment using a medium cut-off dialysis membrane (Theranova) compared with on-line haemodiafiltration treatment with respect to markers of endothelial health (plasma endothelial microvesicle levels, pro-inflammatory and pro-coagulant markers). This study will also compare the 2 treatment modalities with respect to several other outcome measures including patient-reported outcome measures, haemodynamic parameters and advanced glycation end-products.

To date, methods of improving outcomes for haemodialysis patients have focused on improving small molecule clearance (urea); however, the benefits do not appear to be linear and increasing Kt/V above 1.3 shows no benefit. Current dialysis therapies are unable to provide effective clearance of larger "middle molecules" (between 20kDa and 60kDa) and retention of these molecules may be linked to poor outcomes in haemodialysis patients. Medium cut-off (MCO) dialysis membranes have been recently developed to address this area of unmet need and provide an enhanced clearance of some larger middle molecules when compared with high flux haemodialysis (HFHD) and even high volume haemodiafiltration (HDF). The clinical benefit of this therapy is yet to be defined. The aim of this study is to investigate the effect of HDx therapy (expanded haemodialysis therapy through the use of a MCO haemodialysis membrane- Theranova) on vascular endothelial and inflammatory biomarkers compared with high volume HDF therapy. Through the use of endothelial microvesicles (EMV) as a marker of vascular endothelial health, which strongly correlate with cardiovascular outcomes in end-stage real disease (ESRD) patients, this pilot study will take the first steps into exploring whether HDx treatment provides clinical benefits in addition to its simplicity of implementation. Additionally, other important parameters, such as dialysis recovery time, patient-reported outcome measures and volume management will also be explored and compared with high volume HDF.

Hemodialysis, Haemodialysis, Hemodiafiltration, Haemodiafiltration, Dialysis membrane, Endothelial Microvesicles, Pulse Wave Velocity

Participants will receive medium cut-off haemodialysis treatment for 6 months in total (3 times per week treatment).

Participant will remain on their usual on-line haemodiafiltration (HDF) treatment for the 6 month study duration (3 times per week treatment).

Treatment with medium cut-off haemodialysis using the Theranova dialysis membrane 3 times per week for 6 months

Treatment with on-line haemodiafiltration (HDF) 3 times per week for 6 months (Conventional treatment)

Change in endothelial function (composite of endothelial microvesicle levels, pro-inflammatory & pro-coagulant markers)

Change in components of pre-dialysis "middle molecule" panel (this includes beta 2 microglobulin, serum free light chains, leptin, beta trace protein and prolactin)

Change in heart-rate adjusted augmentation index (AI) as measured by non-invasive pulse wave analysis device

Inclusion Criteria: Established on in-centre haemodiafiltration (HDF) for greater than 12 weeks with a minimum of 3 treatment sessions per week Ability to consent Exclusion Criteria: Planned live donor renal transplant within 6 months (with confirmed date) Planned switch in renal replacement modality (ie. to peritoneal dialysis or home haemodialysis) Clinician predicted prognosis < 6 months