In dialysis patients, consider other markers such as hemoglobin and transferrin saturation


INFLAMMATION profoundly influences serum ferritin, making it unreliable as a marker of iron status in hemodialysis patients, a nephrologist-researcher said.

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“So many [hemodialysis] patients have inflammation that ferritin values tend to be so high that they have little to do with iron status,” said Steven Fishbane, MD, chief of nephrology at Winthrop-UniversityHospital in Mineola, N.Y., and professor of medicine at the State University of New York at Stony Brook School of Medicine.


The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines for CKD anemia management state that when serum ferritin values climb above 500 ng/mL, decisions about iron treatment should depend on hemoglobin and transferrin saturation values, responsiveness to erythropoietin-stimulating agents, and how patients feel. Dr. Fishbane said this guidance has been misinterpreted to mean that a serum ferritin level over 500 ng/mL should be the upper limit.


DRIVE study


In the Dialysis patients’ Response to IV iron with Elevated ferritin (DRIVE) study, findings suggest that IV iron can benefit some patients with serum ferritin values above 500 ng/mL, Dr. Fishbane said. The six-week randomized trial compared IV sodium ferric gluconate complex (SFGC) and placebo in 129 epoetin (EPO)-resistant anemic hemodialysis patients with serum ferritin values above 500 ng/mL. The patients had a baseline epoetin dose of least 225 IU/kg/wk or 22,500 IU/wk. At baseline, the SFGC and control groups had mean hemoglobin levels of 10.2 and 10.4 g/dL, respective. At six weeks, the mean hemoglobin levels rose to 11.9 g/dL in the SFGC group and 11.3 g/dL in the control arm, a significant difference between groups. (Investigators presented the findings at the Renal Week conference.)


IV iron superior to oral


Oral iron is insufficient to replenish iron stores, partly because GI absorption of iron is inadequate and adverse effects may lead to non-compliance, Dr. Fishbane explained. A double-blind study of 49 hemodialysis patients randomized to receive iron polysaccharide 150 mg twice daily by mouth or placebo found no difference between in efficacy between the two groups, ac-cording to a report in Clinical Nephrology (1997;48:34-40).


Dr. Fishbane presented data showing that IV iron is more effective than oral iron. For example, in an Israeli study of 39 iron-deficient hemodialysis patients who were not receiving EPO treatment, 20 patients were treated with IV iron gluconate, 10 were treated with oral ferrous iron, and nine had no iron supplementation (controls). All patients were anemic at baseline (hemoglobin level less than 7.8 g/dL) and had severe iron deficiency as indicated by depleted bone marrow iron stores, reduced hemoglobin iron, and a transferrin saturation less than 21%. Follow-up periods were 12 months for controls and 26 months for the oral and IV iron groups.


At the end of the two periods, hemoglobin levels in the control and oral iron groups did not differ significantly from baseline, whereas hemoglobin levels at 26 months in the IV iron recipients reached a mean of 12.6 g/dL. According to the researchers, this evidence “supports both the concept that iron absorption is compromised in chronic uremics and that the parenteral way is the more effective route for iron replacement in this specific group of patients.”


Another study showing the superiority of IV iron enrolled 37 iron-replete renal failure patients starting on EPO. These patients had a hemoglobin concentration less than 8.5 g/dL and initial serum ferritin level of 100-800 µg/L. Subjects were divided into three groups, with 12 patients receiving IV iron dextran 5 mL every two weeks, 13 patients receiving oral ferrous sulphate 200 mg tds, 12 patients not receiving iron. All patients were treated with 25 U/kg of EPO thrice weekly subcutaneously. The mean hemoglobin level in the IV iron group increased from 7.2 g/dL at baseline to 11.9 g/dL at 16 weeks, an increase significantly greater than that experienced by the other two groups, researchers reported in Kidney International (1996;50:1694-1699). In the oral iron and no-iron groups, the hemoglobin level rose from 7.2 and 7.3 g/dL, respectively, at baseline to 10.2 and 9.9 g/dL at 16 weeks.


Although IV iron is superior to oral iron supplementation, Dr. Fishbane noted that oral heme polypeptide may be useful. He cited a study that enrolled 37 patients who had been on maintenance IV iron therapy. The IV iron was discontinued and replaced with oral heme, which patients took for six months. The oral heme polypeptide is absorbed through a different receptor than nonheme (ionic) iron. Over six months, the investigators observed no significant changes in average transferrin saturation or hematocrit, according to a report in the American Journal of Kidney Diseases (2003;42:325-330).


EPO dose reductions


Dr. Fishbane also presented evidence that maintenance IV iron reduces EPO requirements in patients with iron-deficiency anemia related to renal disease. His study, in which patients received iron dextran IV 200 mg once a week for four months, resulted in a 46% decrease in EPO dose. He also cited a study published in Nephrology Dialysis Transplantation (1995;10:2070-2076) showing that hemodialysis patients receiving IV iron saccharate for 12 months had a 70% decrease in EPO dose.