Low-dose continuous iron therapy leads to a positive iron balance and decreased serum transferrin levels in chronic haemodialysis patients.

Background: Iron balance is critical for adequate erythropoiesis, but its optimal therapeutic regimen remains to be defined. Continuous maintenance therapy with iron has been proposed for dialysis patients on recombinant human erythropoietin (rHuEpo) in the hope that the regimen is adequate and safe.

Methods: We determined serum ferritin, transferrin, transferrin saturation (TSAT), serum transferrin receptors, albumin and C-reactive protein (CRP) in a 3-year prospective study in 30 chronic haemodialysis patients on dialysis treatment for 132+/-111 months (18 males, 12 females; mean age 56+/-14 years). Beginning in the year 2000, they regularly received low-dose maintenance iron supplementation (i.v. iron gluconate 31.25 mg/week) for 12 months (Period 1 or first treatment phase), followed by a 6-month withdrawal (Period 2 or stop phase) and then by continuous maintenance iron therapy (i.v. iron gluconate 31.25 mg/week) for another 9 months (Period 3 or re-challenge phase).

Results: A significant increase in serum ferritin and TSAT was observed, with values exceeding 500 ng/ml and 50% in 10/30 (33%) and 7/30 (23%) of subjects, respectively, in Period 1, and in 11 and 5% in Period 3. A significant decrease in serum transferrin was documented during Period 1, followed by an increase in Period 2 and a decrease in Period 3. Serum albumin remained stable. Serum transferrin was always negatively correlated with ferritin (r = -0.41, P<0.001) and weakly correlated with serum transferrin receptors (r = 0.178, P<0.05), but was not correlated with serum albumin or CRP. Regression equations based on pre-treatment serum ferritin values were developed for predicting the value of serum ferritin at any time following the beginning of continuous iron supplementation. They fitted a linear relationship for males (y = 81 + 21.5 x time) and for females (y = 65 + 22 x time). Percentile charts for quantitative tracking of serum ferritin increases and decreases in patients have also been developed from values measured at different times. These charts show box-plot distributions of expected ferritin against time.

Conclusions: Even continuous low-dose maintenance iron therapy, with only 31.25 mg weekly over 1 year, cannot prevent the risk of iron overload in patients with moderate anaemia. Furthermore, this treatment is responsible for decreases in serum transferrin, unrelated to changes in serum albumin, possibly of concern for hypo-transferrinaemia as an independent risk factor for iron toxicity.