title: Optimization of epoetin therapy with intravenous iron therapy in hemodialysis patients.
abstract: Iron deficiency limits the efficacy of recombinant human erythropoietin (rhEPO) therapy in end-stage renal disease (ESRD) patients. Functional iron deficiency occurs with serum ferritin >500 ng/ml and/or transferrin saturation (TSAT) of 20 to 30%. This study examines the effects of a maintenance intravenous iron dextran (ivID) protocol that increased TSAT in ESRD hemodialysis patients from conventional levels of 20 to 30% (control group) to those of 30 to 50% (study group) for a period of 6 mo. Forty-two patients receiving chronic hemodialysis completed a 16- to 20-wk run-in period, during which maintenance ivID and rhEPO were administered in amounts to achieve average TSAT of 20 to 30% and baseline levels of hemoglobin of 9.5 to 12.0 g/dl. After the run-in period, 19 patients randomized to the control group received ivID doses of 25 to 150 mg/wk for 6 mo. Twenty-three patients randomized to the study group received four to six loading doses of ivID, 100 mg each, over a 2-wk period to achieve a TSAT >30% followed by 25 to 150 mg weekly to maintain TSAT between 30 and 50% for 6 mo. Both regimens were effective in maintaining targeted hemoglobin levels. Fifteen patients in the control group and 17 patients in the study group finished the study in which the primary outcome parameter by intention to treat analysis was the rhEPO dose needed to maintain prestudy hemoglobin levels. Maintenance ivID requirements in the study group increased from 176 to 501 mg/mo and were associated with a progressive increase in serum ferritin to 658 ng/ml. Epoetin dose requirements for the study group decreased by the third month and remained 40% lower than for the control group, resulting in an overall cost savings in managing the anemia. Secondary indicators of iron-deficient erythropoiesis were also assessed. Zinc protoporphyrin did not change in either group. Reticulocyte hemoglobin content increased only in the study group from 28.5 to 30.1 pg. It is concluded that maintenance of TSAT between 30 and 50% reduces rhEPO requirements significantly over a 6-mo period.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Anatole
authors.initials: A
authors.lastname: Besarab
authors.affiliation: Department of Pharmacy, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Neeta
authors.initials: N
authors.lastname: Amin
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ahsan
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Vogel
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Gary
authors.initials: G
authors.lastname: Zazuwa
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Stanley
authors.initials: S
authors.lastname: Frinak
authors.affiliation: Life-Chem Labs, Rockleigh, New Jersey.
authors.forename: James J
authors.initials: JJ
authors.lastname: Zazra
authors.affiliation: Department of Pharmacy, Henry Ford Hospital, Detroit, Michigan.
authors.forename: J V
authors.initials: JV
authors.lastname: Anandan
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, Henry Ford Hospital, Detroit, Michigan.
authors.forename: Ajay
authors.initials: A
authors.lastname: Gupta
mesh_terms: D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004921:Erythropoietin / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007275:Injections, Intravenous; D007501:Iron / Q000008:administration & dosage / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011524:Protoporphyrins / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D006435:Renal Dialysis; D012156:Reticulocytes / Q000378:metabolism; D014168:Transferrin / Q000032:analysis
chemical_list: D006454:Hemoglobins; D011524:Protoporphyrins; D011994:Recombinant Proteins; D014168:Transferrin; D004921:Erythropoietin; C017803:zinc protoporphyrin; D007501:Iron