Intravenous iron-gluconate during haemodialysis modifies plasma β₂-microglobulin properties and levels

Background. Intravenous iron replacement therapy is routinely used for correction of anaemia in patients with end-stage renal failure. Free or labile iron, present both in parenteral iron formulations and in blood of haemodialysis (HD) patients, has the potential to induce severe oxidative processes. This study evaluated the acute in vivo effect of intravenous iron administration on the oxidation of plasma β₂-microglobulin (β₂m) and on its plasma levels after HD. Methods. Iron-gluconate was administered intravenously to 14 patients receiving HD with low-flux cellulose-triacetate membranes during the first hour of the 4 h HD treatment. Each patient underwent three different dialysis treatments, during which an infusion of 62.5, 125 or 0 mg (control) of iron-gluconate was administered in random order. Plasma β₂m levels and iron parameters were monitored immediately before and after each HD treatment. The molecular isoforms of β₂m were studied by two-dimensional gel electrophoresis and western analysis. Levels of oxidized β₂m were evaluated by reaction with 2,4-dinitrophenylhydrazine and western analysis. Results. Both doses of iron-gluconate caused remarkable changes in the molecular properties of β₂m, including shift in isoelectric point, molecular mass and degree of oxidation. Iron administration also limited the decline in plasma β₂m levels to <7.5%, compared with 27.9±2.7% during HD without iron. Conclusions. Intravenous iron-gluconate led to a characteristic increase in molecular weight and in negative charge of β₂ m, both of which can be assumed to be consistent with reduced membrane sieving coefficients and membrane adsorption, and thus with reduced clearance of β₂m.