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Titolo Removal of uraemic plasma factor(s) using different dialysis modalities reduces phosphatidylserine exposure in red blood cells
Autore Bonomini M, Ballone E, Di Stante S. et al. Uni Chieti (I); Sigma Tau, Rome (I); Hoffman-La Roche, Basel (CH)
Referenza Nephrol Dial Transplant 2004; 19: 68-74
Contenuto Introduction: Exposure of aminophospholipid phosphatidylserine (PS) on the outer surface of erythrocyte membranes is a known phenomenon for the physiological clearance of aged erythrocytes from the circulation by the reticulo-endothelial system. This phenomenon is increased in uremia and may be involved in the pathophysiology of anaemia by promoting abnormal erythrocyte interaction Methods: In this prospective, cross-over, patient control, monocenter study, 8 CKD patients were treated with HD or HDF on line (using F70S, FX80 in HD and F70S and FX80 in HDF on line). Each treatment was continued for 1 week and the order of treatment was based on a Latin square model. Samples (blood and ultrafiltrate) were collected for analysis during the third treatment. Sampling times were 5 min after session start, at 120 min and at the end. Patients plasma and ultrafiltrate were incubated (4 hrd, 37 °C) in ABO/Rh-compatible, isolated normal erythrocytes. In some experiments ultrafiltrate was first passed through a sieving filter (cut-off 10 or 20 kD). As control normal erythrocytes were resuspended in autologous plasma (Htc 50%). PS exposure was studied by flow-cytometric assay using fluorescein isothiocyanate-labelled annexin V, a high affinity ligand for PS. Using the same experimental conditions, the authors incubated ultrafiltrate fractions obtained from two separate techniques: gel filtration that allows to separate molecules on the basis of their molecular weight and partition serparation using hydrophilic/hydrophobic solvents to separate molecules on the basis of their molecular weight and partition separation using hydrophilic/hydrophobic solvents to separate molecules according to their polarity. Results and conclusions: HD significantly decreased the exposure of PS in erythrocytes after 4 hr without difference between F70S and FX80. This effect was even more marked after HDF on line: Of interest, there was a statistical significant difference between F70S and FX80. The factors have a molecular weight around 20kD, are highly lipophilic in nature and are sensitive to freeze and thawing. Comments: There was an effect of dialysis dose (see the differebce between HD and HDF on line, whatever the dialyser). The significant effect of Helixone in HDF on line was not dependent on the dose and is therefore of relevance. If confirmed, this would provide a rational basis for an increased half life or erythrocytes in CKD patients treated with on line HDF modalities. Unfortunately, these studies can not be multicentric (due to the lability of the ultrafiltrable compunds). However, if this results are to be confirmed in a larger cohort of patients, it would be the first biological explanation for a superiority of HDF on lin4 on high flux dialysis. Finally, full recognition of the factor(s) and the inproved elimination with Helixone may provide further support to the concept of membrane nanostructuring.
Data 21.04.2004
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