Increased erythrocyte phosphatidylserine exposure in chronic renal failure

The appearance of phosphatidylserine, an aminophospholipid normally confine d to the inner monolayer, at the outer leaflet of red cell membrane may hav e several pathophysiologic implications. This study examines erythrocyte ph osphatidylserine exposure in chronic renal failure (CRF) patients on conser vative treatment or on dialysis, to assess possible alterations to phosphol ipid asymmetry in a condition associated with a state of deranged red cell function. A significant increase in phosphatidylserine expressing erythrocy tes was found in undialyzed patients with CRF (2.32%) and patients on hemod ialysis (3.06%) and on peritoneal dialysis (2.14%) compared with control su bjects (0.68%). In undialyzed CRF patients, a strong correlation (r = 0.903 ) was found between the percentage of phosphatidylserine-expressing red cel ls and the serum creatinine concentration. The increased exposure of phosph atidylserine in uremic erythrocytes may be due to inhibition of phosphatidy lserine transport from the outer to The inner leaflet of plasma membrane an d may promote an increased erythrophagocytosis. In reconstitution experimen ts, normal erythrocytes showed an increase in phosphatidylserine-expressing cells when incubated in uremic plasma (3.2% after 2 h versus 1.1% at begin ning of incubation), whereas phosphatidylserine-positive uremic erythrocyte s decreased when resuspended in normal plasma (2.03% after 2 h and 1.65% af ter 8 h versus 2.9% at beginning of incubation). Preliminary characterizati on of the putative uremic compound(s) indicates a molecular weight between 10,000 and 20,000, as well as heat instability. These findings show an impa irment of erythrocyte membrane phospholipid asymmetry in CRF patients, rega rdless of the dialysis treatment. Such abnormality seems related to the ure mic slate and could contribute to the red cell pathology present in CRF.