NDT Advance Access originally published online on June 14, 2005
Nephrology Dialysis Transplantation 2005 20(9):1963-1969; doi:10.1093/ndt/gfh907
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Intravenous iron-gluconate during haemodialysis modifies plasma ß2-microglobulin properties and levels
1 Eliachar Research Laboratory and 2 Nephrology Department, Western Galilee Hospital, Nahariya and 3 Bruce Rappaport School of Medicine, Technion, Haifa, Israel
Correspondence and offprint requests to: Professor Batya Kristal, Head of Nephrology and Hypertension Department, Western Galilee Hospital, Nahariya, 22100, Israel. Email: Batya.Kristal{at}naharia.health.gov.il
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 ß2-microglobulin (ß2m) 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 ß2m levels and iron parameters were monitored immediately before and after each HD treatment. The molecular isoforms of ß2m were studied by two-dimensional gel electrophoresis and western analysis. Levels of oxidized ß2m 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 ß2m, including shift in isoelectric point, molecular mass and degree of oxidation. Iron administration also limited the decline in plasma ß2m 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 ß2m, both of which can be assumed to be consistent with reduced membrane sieving coefficients and membrane adsorption, and thus with reduced clearance of ß2m.
Keywords: advanced glycation end-products; carbonyl; iron-gluconate; low flux; protein oxidation
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