Abstract
Uremic toxins play a pathological role in atherosclerosis and represent an important risk factor in dialysis patients. Online hemodiafiltration (HDF) has been introduced to improve the clearance of middle- and large-molecular-weight solutes (>500 Da) and has been associated with reduced cardiovascular mortality compared to standard hemodialysis. This non-randomized, open-label observational study will explore the efficacy of two dialyzers currently used for online HDF, a polysulfone-based high-flux membrane, and a cellulose triacetate membrane, in hemodialysis patients with signs of middle-molecule intoxication or intradialytic hypotension. In particular, the two filters will be evaluated for their ability in uremic toxin removal and modulation of inflammatory status. Sixteen subjects in standard chronic bicarbonate hemodialysis requiring a switch to online HDF in view of their clinical status will be enrolled and divided into two treatment arms, according to the previous history of hypersensitivity to polysulfone/polyethersulfone dialysis filters and hypersensitivity to drugs or other allergens. Group A will consist of 16 patients without a previous history of hypersensitivity and will be treated with a polysulfone filter (Helixone FX100), and group B, also consisting of 16 patients, with a previous history of hypersensitivity and will be treated with asymmetric triacetate (ATA; SOLACEA 21-H) dialyzer. Each patient will be followed for a period of 24 months, with monthly assessments of circulating middle-weight toxins and protein-bound toxins, markers of inflammation and oxidative stress, lymphocyte subsets, activated lymphocytes, and monocytes, cell apoptosis, the accumulation of advanced glycation end-products (AGEs), variations in arterial stiffens measured by pulse wave velocity (PWV), and mortality rate. The in vitro effect on endothelial cells of uremic serum collected from patients treated with the two different dialyzers will also be investigated to examine the changes in angiogenesis, cell migration, differentiation, apoptosis and proliferative potential, and gene and protein expression profile. The expected results will be a better awareness of the different effects of polysulfone gold-standard membrane for online HDF and the new ATA membrane on the removal of uremic toxins removal and inflammation due to blood–membrane interaction.
Highlights
Patients with end-stage renal disease (ESRD) have a significantly increased cardiovascular mortality rate compared to the general population [1,2]
There is some evidence to indicate that HDF with high convection volumes reduces cardiovascular mortality compared to standard hemodialysis [11,12,13]
Monthly laboratory assays, namely circulating medium-molecular-weight uremic toxins and toxins linked to plasma proteins, inflammation markers and cytokines, analysis of lymphocyte subsets, activated lymphocytes and monocytes, and cell apoptosis rate; monthly assessment of accumulation of advanced glycation end-products (AGEs) as an index of metabolic and oxidative stress; infectious complications; cardiovascular complications; eventual kidney transplantation; possible interruption of online HDF and the switch to another dialysis technique; need for hospitalization; patient survival; in vitro effect on endothelial cells of uremic serum collected from patients treated with the two different dialyzers on angiogenesis, cell migration, differentiation, apoptosis and proliferative potential, and gene and protein expression profile; monthly bioimpedance analysis (BIA); monthly measurement of changes in arterial stiffness by pulse wave velocity (PWV)
Summary
Patients with end-stage renal disease (ESRD) have a significantly increased cardiovascular mortality rate compared to the general population [1,2]. States Renal Data System (USRDS) report, in 2018, the prevalence of cardiovascular disease (CVD) in the United States, adjusted for age, sex, and race, was 37.5% of subjects without chronic kidney disease (CKD) vs 63.4% of patients with stages 1–2 of CKD, 66.6% of patients with stage 3 CKD, and 75.3% of patients with stages 4–5 of CKD [3]. There is some evidence to indicate that HDF with high convection volumes (above 20 L) reduces cardiovascular mortality compared to standard hemodialysis [11,12,13]. Since middle-molecule clearance through HDF is still inferior compared to a native kidney, the search for novel dialysis technologies is under constant development [14,15]
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