BACKGROUND: The percentage of hypochromic red blood cells (RBC), defined as those with a cellular haemoglobin < 28 g/dl has been suggested to be a sensitive marker of functional iron deficiency in maintenance haemodialysis (HD) patients. Thus, during rHuEpo therapy an increase in hypochromic RBC to > 10% would indicate that more intensive iron supplementation may be required. METHODS: We investigated 70 HD patients 57.1 +/- 15.3 years old and on maintenance HD for 66.3 +/- 47.9 months without blood loss from gastrointestinal bleeding or from the vascular access, without surgery and without infectious disease or malignancy. During the study period of 12 weeks, each patient received in i.v. dose of 800 mg ferrogluconate. Haemoglobin, haematocrit, and the percentage of hypochromic RBC were measured before and every 4 weeks after the start of the study; serum ferritin, zinc protoporphyrin (ZPP) and C-reactive protein (CRP) were measured at the beginning (baseline) and end of the study. RESULTS: At baseline the percentage of hypochromic RBC was < or = 5.0% in 28 patients, > 5.0 and < or = 10.0% in 25 patients and > 10.0% in 17 patients, suggesting functional iron deficiency in at least 42 patients. Nine patients had serum ferritin values < 100 micrograms/1; nonetheless in these patients the median percentage of hypochromic RBC was 5.9% (range 0.9-14.3%), indicating that an absolute iron deficiency can occur in the presence of normal amounts of hypochromic RBC. There was a significant correlation between serum ferritin levels and hypochromic RBC at the end, but not at the beginning, of the study. However, there was no correlation between ZPP and hypochromic RBC at any time during the study. During i.v. iron supplementation the rHuEpo dose could be reduced by 8.5% in patients with hypochromic RBC < or = 5.0%, by 11.3% in patients with hypochromic RBC > 5.0 and < or = 10.0% and by 23.4% in patients with hypochromic RBC > 10.0%, demonstrating the benefit of i.v. iron in patients with functional iron deficiency. In HD patients in whom serum ferritin levels remained below 290 micrograms/l until the end of the study, a significant reduction of the rHuEpo dosage could be obtained during i.v. iron therapy. This was not the case in patients with serum ferritin > 290 micrograms/l after iron supplementation. We found that the percentage of hypochromic RBC is the most sensitive parameter for predicting hyporesponsiveness in CRP-positive patients. HD patients with hypochromic RBC > 6% and low to moderate increases in serum ferritin levels after i.v. iron supplementation significantly benefit from i.v. iron therapy compared to HD patients with hypochromic RBC < 6%. CONCLUSIONS: Two different aspects should be taken into consideration in HD patients treated with rHuEpo and concomitant i.v. iron therapy: (1) response of the erythropoietic system to rHuEpo, and (2) adequate delivery of the supplemented iron to the erythropoietic system. The patient's percentage of hypochromic RBC and increase in serum ferritin after i.v. iron supplementation should be used to decide whether or not i.v. iron should be given and to monitor this type of therapy in HD patients.
BACKGROUND: The percentage of hypochromic red blood cells (RBC), defined as those with a cellular haemoglobin < 28 g/dl has been suggested to be a sensitive marker of functional iron deficiency in maintenance haemodialysis (HD) patients. Thus, during rHuEpo therapy an increase in hypochromic RBC to > 10% would indicate that more intensive iron supplementation may be required. METHODS: We investigated 70 HDpatients 57.1 +/- 15.3 years old and on maintenance HD for 66.3 +/- 47.9 months without blood loss from gastrointestinal bleeding or from the vascular access, without surgery and without infectious disease or malignancy. During the study period of 12 weeks, each patient received in i.v. dose of 800 mg ferrogluconate. Haemoglobin, haematocrit, and the percentage of hypochromic RBC were measured before and every 4 weeks after the start of the study; serum ferritin, zinc protoporphyrin (ZPP) and C-reactive protein (CRP) were measured at the beginning (baseline) and end of the study. RESULTS: At baseline the percentage of hypochromic RBC was < or = 5.0% in 28 patients, > 5.0 and < or = 10.0% in 25 patients and > 10.0% in 17 patients, suggesting functional iron deficiency in at least 42 patients. Nine patients had serum ferritin values < 100 micrograms/1; nonetheless in these patients the median percentage of hypochromic RBC was 5.9% (range 0.9-14.3%), indicating that an absolute iron deficiency can occur in the presence of normal amounts of hypochromic RBC. There was a significant correlation between serum ferritin levels and hypochromic RBC at the end, but not at the beginning, of the study. However, there was no correlation between ZPP and hypochromic RBC at any time during the study. During i.v. iron supplementation the rHuEpo dose could be reduced by 8.5% in patients with hypochromic RBC < or = 5.0%, by 11.3% in patients with hypochromic RBC > 5.0 and < or = 10.0% and by 23.4% in patients with hypochromic RBC > 10.0%, demonstrating the benefit of i.v. iron in patients with functional iron deficiency. In HDpatients in whom serum ferritin levels remained below 290 micrograms/l until the end of the study, a significant reduction of the rHuEpo dosage could be obtained during i.v. iron therapy. This was not the case in patients with serum ferritin > 290 micrograms/l after iron supplementation. We found that the percentage of hypochromic RBC is the most sensitive parameter for predicting hyporesponsiveness in CRP-positive patients. HDpatients with hypochromic RBC > 6% and low to moderate increases in serum ferritin levels after i.v. iron supplementation significantly benefit from i.v. iron therapy compared to HDpatients with hypochromic RBC < 6%. CONCLUSIONS: Two different aspects should be taken into consideration in HDpatients treated with rHuEpo and concomitant i.v. iron therapy: (1) response of the erythropoietic system to rHuEpo, and (2) adequate delivery of the supplemented iron to the erythropoietic system. The patient's percentage of hypochromic RBC and increase in serum ferritin after i.v. iron supplementation should be used to decide whether or not i.v. iron should be given and to monitor this type of therapy in HDpatients.