BACKGROUND: Middle molecular weight uraemic toxins are considered to play an important role in vascular dysfunction and cardiovascular outcomes in end-stage renal disease (ESRD) patients. Recent dialysis techniques based on convection, specifically high-efficiency on-line haemodiafiltration (HDF), enhance the removal of middle molecular weight toxins and reduce all-cause mortality in haemodialysis (HD) patients. However, the mechanisms of these improved outcomes remain to be established. METHODS: This prospective study randomly assigned 42 ESRD patients to switch from high-flux HD to high-efficiency on-line HDF (n=22) or to continue HD (n=20). Brachial artery endothelium-dependent flow-mediated dilatation, central pulse pressure, carotid artery intima-media thickness (IMT), internal diastolic diameter and distensibility and circulating markers of uraemia, inflammation and oxidative stress were blindly assessed before and after a 4-month follow-up. RESULTS:Brachial flow-mediated dilatation and carotid artery distensibility increased significantly in the HDF group compared with HD, while carotid IMT and diameter remained similar. HDF decreased predialysis levels of the uraemic toxins β2-microglobulin, phosphate and blood TNFα mRNA expression. Oxidative stress markers were not different between the HD and HDF groups. Blood mRNA expression of protein kinase C β2, an endothelial NO-synthase (eNOS) inhibitor, decreased significantly with HDF. CONCLUSIONS: High-efficiency on-line HDF prevents the endothelial dysfunction and stiffening of the conduit arteries in ESRD patients compared with high-flux HD. HDF decreases uraemic toxins, vascular inflammation, and is associated with subsequent improvement in eNOS functionality. These results suggest that reduced endothelial dysfunction may be an intermediate mechanism explaining the beneficial outcomes associated with HDF.
RCT Entities:
BACKGROUND: Middle molecular weight uraemic toxins are considered to play an important role in vascular dysfunction and cardiovascular outcomes in end-stage renal disease (ESRD) patients. Recent dialysis techniques based on convection, specifically high-efficiency on-line haemodiafiltration (HDF), enhance the removal of middle molecular weight toxins and reduce all-cause mortality in haemodialysis (HD) patients. However, the mechanisms of these improved outcomes remain to be established. METHODS: This prospective study randomly assigned 42 ESRDpatients to switch from high-flux HD to high-efficiency on-line HDF (n=22) or to continue HD (n=20). Brachial artery endothelium-dependent flow-mediated dilatation, central pulse pressure, carotid artery intima-media thickness (IMT), internal diastolic diameter and distensibility and circulating markers of uraemia, inflammation and oxidative stress were blindly assessed before and after a 4-month follow-up. RESULTS: Brachial flow-mediated dilatation and carotid artery distensibility increased significantly in the HDF group compared with HD, while carotid IMT and diameter remained similar. HDF decreased predialysis levels of the uraemic toxins β2-microglobulin, phosphate and blood TNFα mRNA expression. Oxidative stress markers were not different between the HD and HDF groups. Blood mRNA expression of protein kinase C β2, an endothelial NO-synthase (eNOS) inhibitor, decreased significantly with HDF. CONCLUSIONS: High-efficiency on-line HDF prevents the endothelial dysfunction and stiffening of the conduit arteries in ESRDpatients compared with high-flux HD. HDF decreases uraemic toxins, vascular inflammation, and is associated with subsequent improvement in eNOS functionality. These results suggest that reduced endothelial dysfunction may be an intermediate mechanism explaining the beneficial outcomes associated with HDF.
Authors: Luca Zanoli; Paolo Lentini; Marie Briet; Pietro Castellino; Andrew A House; Gerard M London; Lorenzo Malatino; Peter A McCullough; Dimitri P Mikhailidis; Pierre Boutouyrie Journal: J Am Soc Nephrol Date: 2019-04-30 Impact factor: 10.121
Authors: Ayşe Ağbaş; Nur Canpolat; Salim Çalışkan; Alev Yılmaz; Hakan Ekmekçi; Mark Mayes; Helen Aitkenhead; Franz Schaefer; Lale Sever; Rukshana Shroff Journal: PLoS One Date: 2018-06-18 Impact factor: 3.240
Authors: Robin W M Vernooij; Way Law; Sanne A E Peters; Bernard Canaud; Andrew Davenport; Muriel P C Grooteman; Fatih Kircelli; Francesco Locatelli; Francisco Maduell; Marion Morena; Menso J Nubé; Ercan Ok; Ferran Torres; Mark Woodward; Peter J Blankestijn; Michiel L Bots Journal: BMC Nephrol Date: 2021-02-25 Impact factor: 2.388