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    The effects of a novel medium-cut-off haemodialysis membrane on biomarkers of vascular health in dialysis patients

    Herring, Annie Elizabeth (2023) The effects of a novel medium-cut-off haemodialysis membrane on biomarkers of vascular health in dialysis patients. Doctoral thesis (PhD), Manchester Metropolitan University.

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    Abstract

    Introduction: Healthy kidneys filter metabolic waste molecules of up to 60kDa from the blood into the urine, whereas conventional haemodialysis membranes are only able to clear molecules of up to 20kDa. Retention of larger molecules in patients on dialysis is linked to endothelial dysfunction and inflammation leading to increased cardiovascular disease (CVD) risk. Novel medium cut-off dialysis membranes (MCO) have been developed that can more effectively clear middle-sized molecules (≤45kDa). Methods: This pilot clinical trial includes 50 patients randomised into two groups; dialysis using the novel MCO versus Heamodiafiltration Blood samples were taken at 0 and 6 months and the levels of endothelial microvesicles (EMVs) were measured as a marker of endothelial dysfunction using flow cytometry. Cytokines, including TNF-α, VEGF, Interleukins 6 and 10, VCAM and I-CAM were measured in serum using Magnetic multiplex assays. Sera isolated from 8 patients from both treatment groups were used to determine their effect on Human Umbilical Vein Endothelial cell (HUVEC) function using in vitro assays of angiogenesis, migration and cell viability. Calcification-related serum markers were measured in sera from patients in the HDF and MCO groups at 0 and 6 months. The markers included BMPs 2, 4 and 9, SOST/Sclerostin (n=10/group); osteopontin, osteoprotegerin and FGF-23 (n=25/group) and were measured using magnetic multiplex assays (Bio-Techne, UK). Results and conclusions: EMV levels decreased significantly over 6 months in the MCO treatment group compared to the patients that underwent 6 months of HDF treatment (p<0.05). Levels of cytokines and calcification related markers over 6 months remained comparable between the two membranes. Cell viability, angiogenesis and cell migration were similar in HUVECs following exposure to sera from patients on standard HDF or MCO dialysis. These results show that the MCO membrane provides a non-inferior performance when assessing vascular health using biomarker and cell-culture data.

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