Nephrol Dial Transplant (2004) 19: 68-74
© ERA–EDTA 2003; all rights reserved
Original Article
Removal of uraemic plasma factor(s) using different dialysis modalities reduces phosphatidylserine exposure in red blood cells
1Institute of Nephrology and 2Biostatistical Laboratory, Department of Medicine, 3Department of Biomedical Sciences and 4Centro Studi sull’Invecchiamento, Department of Biomedical Sciences, G. d’Annunzio University, Chieti, 5Department of Metabolism and Endocrinology, Sigma Tau Pharmaceuticals, Pomezia, Rome, Italy and 6Department of Metabolic Diseases, F. Hoffmann-La Roche, Pharmaceutical Division, Basel, Switzerland
Correspondence and offprint requests to: Mario Bonomini, MD, Institute of Nephrology, SS Annunziata University Hospital, Via dei Vestini, 66013 Chieti, Italy. Email: m.bonomini{at}nephro.unich.it
Background. Solute(s) retained during uraemia cause increased exposure of aminophospholipid phosphatidylserine (PS) on the outer surface of erythrocyte membranes, and this phenomenon may be involved in the pathophysiology of uraemia by promoting abnormal erythrocyte interactions.
Methods. We examined in a prospective randomized cross-over fashion the ability of various dialysis modalities to remove the circulating uraemic factor(s) causing increased PS externalization in red cells. Each patient was treated with haemodialysis (HD) and with on-line haemodiafiltration (HDF) using standard high-flux polysulphone membranes or with the new polisulphone-based Helixone membrane to compare the effects of dialysis technique and membrane type on PS exposure. Removal of PS was assessed indirectly by measuring PS-expressing normal erythrocytes exposed to uraemic plasma or to ultrafiltrate obtained at various time points during the extracorporeal session.
Results. Removal of the uraemic plasma factor(s) causing PS exposure was demonstrated by the reduced ability of uraemic plasma at the end of dialysis to induce PS exposure in normal erythrocytes, and by the capacity of ultrafiltrate from the dialysate side of the dialyzer membrane to markedly increase PS-positive red cells. However, the degree of removal varied according to the dialyzer type and to dialysis technique. Removal was greater for on-line HDF using the Helixone membrane, intermediate and comparable with HD with Helixone and with on-line HDF using standard polysulphone, and lower for HD using polysulphone membrane. The putative uraemic compound causing PS exposure seems to be highly lipophilic, somehow associated with plasma proteins, and apparently having a molecular weight between 10 and 10.8 kDa.
Conclusions. Uraemia is associated with retention of compound(s) that are lipophilic, possibly protein-bound and which cause an abnormal exposure of PS in erythrocytes. Our findings, that such compound(s) can be removed during dialysis and at higher rates with convection techniques, indicate a potential benefit for uraemic patients. The present results also seem to confirm the marked ability of high-flux Helixone membranes to eliminate high molecular weight solutes.
Keywords: erythrocyte; haemodialysis; helixone; high molecular weight solutes; on-line haemodiafiltration; phosphatidylserine