Labile iron in parenteral iron formulations and its potential for generating plasma nontransferrin-bound iron in dialysis patients

Background Labile plasma iron (LPI) associated with iron supplementation has been implicated in complications found in dialysis patients. As LPI can potentially catalyse oxygen radical generation, we determined the presence of labile iron in the parenteral preparations and the frequency of occurrence of LPI in dialysis patients. Design The capacity to donate iron to apotransferrin (apo-) or to the chelator desferrioxamine (DFO) was measured with fluorescein-Tf (Fl-Tf) and Fl-DFO, respectively. Those probes undergo quenching upon binding to iron. Iron-catalysed generation of oxidant species was determined with dihydrorhodamine. Plasma nontransferrin-bound iron (NTBI), here termed LPI, was determined by mobilization of iron from low-affinity binding sites with oxalate, followed by its quantification with Fl-Tf in the presence of Ga(III). Results Normal individuals and most (80%) dialysis patients, analysed at least 1 week after iron supplementation showed no detectable ( 0·2 µm), in some cases weeks after iron administration. LPI levels correlated best (r2 = 0·9) with Tf saturation. The iron preparations contained 2–6% low molecular weight and redox-active iron, most of which is chelated by Tf. Conclusions Parenteral iron formulations contain a small but significant fraction of redox-active iron, most of which is scavenged by apo-Tf within