'Oversaturation' of transferrin after intravenous ferric gluconate (Ferrlecit(R)) in haemodialysis patients.

BACKGROUND: Chronic haemodialysis causes blood loss and iron-deficiency. This can be corrected with intravenous preparations, e.g. sodium ferric-gluconate (FeGl). In two patents complaints of hypotension and malaise during FeGl infusion coincided with high levels of serum iron and a calculated transferrin iron saturation above 100%. Iron toxicity could be the cause of these complaints. Free iron is known to aggravate the toxicity of free radicals and other reactive oxygen products that are constantly formed in the body. We compared four rates of FeGl infusion with regard to iron parameters.
METHODS: 20 dialysis patients received a total of 26 infusions of FeGl. A rapid infusion of 135 mg (Protocol A (n=10)) or 62.5 mg (Protocol B (n=7)) of FeGl was given during the last 30 min of dialysis. A slow infusion of 125 mg (Protocol C (n=9)) or 62.5 mg (Protocol D (n=10)) was given during 4 or 4.5 h of dialysis. Blood was taken at regular intervals, before, during, and after dialysis for determination of serum iron, transferrin, ferritin, haematocrit, total protein, albumin, and lactate dehydrogenase (LDH). Transferrin saturation was calculated from transferrin and serum iron.
RESULTS: With rapid infusion A (125 mg) the highest levels of serum iron (median 120 (range 40-159) micromol/l) and transferrin saturation (207 (84-331)%) were seen at the end of the infusion. These were significantly higher than the peak levels with B, C, and D (P</=0.03). With rapid infusion B (62.5 mg), peak levels were intermediately high (serum iron 61 (50-96) micromol/l; transferrin saturation 118 (91-174)%). With slow infusion C (125 mg) similar peak levels were seen (serum iron 83 (43-106) micromol/l; transferrin saturation 141 (88-172)%). With slow infusion D (62.5 mg), the lowest peak levels were seen (serum iron 38 (31-55) micromol/l; transferrin saturation 78 (43-92)%). These levels were significantly lower than those with A, B and C (P<=0.002). Only with D all patients showed a transferrin saturation lower than 100%. Ferritin was increased before the next dialysis in all patients. LDH was not significantly elevated during any infusion.
CONCLUSIONS: The commonly used rapid infusion rate (A) of FeGl causes 'oversaturation' of transferrin. This is compatible with iron toxicity due to free iron which may explain our patients' complaints. Free iron cannot be measured directly. LDH as a crude measure of cell damage was not elevated. Better measurements to prove free iron toxicity, like lipid peroxides, are not yet readily available. Infusion during a longer period at a lower dose (D) is effective and eliminates 'Oversaturation' of transferrin and probably the danger of iron toxicity.