Parenteral Iron Regimens In Hemodialysis Patients

Nutrition Research Newsletter, Sept, 1999 by Anatole Besarab, Joseph Kaiser, Stan Frinak

Recombinant human erythropoietin (rHuEPO) has greatly improved the management of anemia in patients with end-stage renal disease (ESRD). However, many patients are still unable to reach their target hemoglobin (Hb) level despite adequate rHuEPO doses. It has been identified that the major cause of this problem is the absence of available iron to support the increased erythropoiesis. Transferrin saturation (TSAT) less than 20% or a ferritin level less than 100 ng/mL are the current threshold values for iron repletion in patients with ESRD. However, recent investigations have uncovered that these markers may not be accurate. The only way to definitively rule out functional iron deficiency is by evaluating the erythroid response to additional iron administration.

Iron has been traditionally administered by an intermittent-administration regimen that is based on individual need. The National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) Anemia Workgroup Guidelines recommend a proactive intravenous iron maintenance regimen, as opposed to the traditional method. A recent study sponsored by the National Kidney Foundation is the first to directly compare a maintenance therapy regimen with the standard intermittent treatment. Researchers also examined the changes with time in serum concentrations of iron, iron binding, and ferritin between the two regimens.

Chronic hemodialysis patients on maintenance rHuEPO therapy for anemia were eligible for this open, prospective, non-randomized, longitudinal efficacy study. Twenty-four patients were enrolled into this trial of intravenous iron dextran therapy comparing an intermittent as-needed regimen to a maintenance iron regimen. The subjects were divided into two groups, matched for age, sex, cardiac disease, and serum parathyroid hormone (PTH) levels. The recombinant epoetin dose was adjusted in all patients every four to eight weeks in an effort to maintain Hb levels between 10-11 g/dL. The 12 patients in the continuous maintenance iron dextran therapy group received an initial intravenous iron dextran pulse of 300-500 mg to achieve a TSAT greater than 30%, followed by 25-100 mg every one to two weeks thereafter to maintain a TSAT level between 30-50%. Blood counts were measured by standard methods. These patients had a statistically significant decrease in the amount of fHuEPO needed to maintain Hb levels within a normal range, compared with the 12 subjects receiving the intermittent need-based dosing. Eleven of the 16 patients met the TSAT criteria for iron therapy, and 12 of the 16 met the ferritin criteria for iron therapy. Only eight patients were able to meet both criteria.

The results of this study clearly indicate that, compared with the standard intermittent need-based dosing strategy, continuous-maintenance intravenous iron reduces the amount of rHuEPO needed to sustain a desired Hb level in anemic chronic hemodialysis patients. This longitudinal study displays a mismatch between the amount of iron needed and the epoetin dose required for optimal erythropoiesis with use of the as-needed intermittent iron therapy. The results also suggest that weekly maintenance regimens can be continued so long as single doses less than 100 mg are administered each week. The safety of continuous-maintenance intravenous iron therapy was equivocal to the safety of intermittent therapy. Researchers were unable to assess infection risks or morbidity/mortality risks from receiving frequent doses of iron dextran, due to the small sample size. It was concluded that it is more effective to administer iron continuously rather than intermittently.

Anatole Besarab, Joseph Kaiser, Start Frinak, A Study of Parenteral Iron Regimens in Hemodialysis Patients, Am J Kidney Diseases, 34(1): 21-28 (July 1999) [Correspondence: Anatole Besarab, MD, Division of Nephrology and Hypertension, CFP-5, Henry Ford Hospital, 2 799 W. Grand Blvd., Detroit, MI 48202. E-mail: abesarab@pol.net.]