Mathematical approach for estimating iron needs in hemodialysis patients on erythropoietin therapy

Functional iron deficiency occurs when recombinant human erythropoietin (rHuEPO) accelerates erythropoiesis to an extent that the iron availability cannot meet the anticipated demand. Such a phenomenon will reduce the optimal response to rHuEPO. To estimate the iron needs of functional iron deficiency in hemodialysis patients on rHuEPO therapy, we utilized a mathematical method. Forty hemodialysis patients were examined in the study, and all had a baseline serum ferritin (SF) level > 100 microg/l. They were stratified into patients with a transferrin saturation (TfS) value > or = 25% (group I) and those below this value (group II). The treatment protocol consisted of rHuEPO therapy in the two groups for 6 months and iron supplement only in group II. The target hemoglobin level was 10.5 g/dl, and iron metabolism indices were analyzed prior to and following therapy. The results showed (1) in group I (n = 20) hemoglobin rose from 7.5 +/- 0.9 to 10.7 +/- 0.7 g/dl (p < 0.01) and the mean SF level declined from 1,583 +/- 997 to 968 +/- 664 mg (p < 0.01); (2) in group II (n = 20) hemoglobin also increased from 7.8 +/- 0.9 to 10.6 +/- 0.8 g/dl (p < 0.01) following iron supplement, while the SF rose from 183 +/- 70 to 326 +/- 125 mg (p < 0.01); (3) TfS was significantly elevated in group II following iron therapy (18.9 +/- 4.8 vs. 34.5 +/- 9.1%, p < 0.01), and (4) the nomogram showed a sensitivity of 80%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 83% in estimating the iron status before rHuEPO therapy. We conclude that SF levels reflect iron stores and that TfS < 25% is an index of functional iron deficiency. Iron supplementation is not necessary in patients with SF > 100 microg/l and TfS > or = 25%. It seems rational to provide intravenous iron in EPO-resistant patients with functional iron deficiency (SF > 100 microg/l, TfS < 25%). This paper illustrates the importance that accurate assessment of iron needs by a mathematical method would enhance treatment efficacy and avoid iron overload in hemodialysis patients on rHuEPO therapy.