Intravenous ascorbic acid as an adjuvant therapy for recombinant erythropoietin in hemodialysis patients with hyperferritinemia

Der Cherng Tarng, Wei Yau-Huei, Tung Po Huang, Benjamin I.T. Kuo, Wu Chang Yang

Research output: Contribution to journalJournal Article peer-review

110 Scopus citations

Abstract

Background. Inadequate iron mobilization and defective iron utilization may cause recombinant erythropoietin (rEPO) hyporesponsiveness in hemodialysis (HD) patients with iron overload. We have demonstrated that intravenous ascorbic acid (IVAA), but not intravenous iron medication, can effectively circumvent the functional iron-deficient erythropoiesis associated with iron overload in HD patients. However, it is uncertain whether all HD patients with hyperferritinemia will consistently respond to IVAA and which index may indicate functional iron deficiency in the special entity. Therefore, a prospective study was conducted to establish the guidelines for IVAA adjuvant therapy. Methods. Sixty-five HD patients with serum ferritin levels of more than 500 μg/liter were recruited and divided into the control (N = 19) and IVAA (N = 46) groups. IVAA patients with a hematocrit (Hct) of less than 30% received 300 mg of ascorbic acid three times per week for eight weeks. Controls had a Hct of more than 30% and did not receive the adjuvant therapy. Red blood cell and reticulocyte counts, iron metabolism indices, erythrocyte zinc protoporphyrin (E-ZPP), and the concentrations of plasma ascorbate and oxalate were examined before and following the therapy. Results. Thirteen patients (four controls and nine IVAA patients) withdrew by the end of the study. Eighteen patients had a dramatic response to IVAA with a significant increase in their hemoglobin and reticulocyte index and a concominant 24% reduction in rEPO dose after eight weeks. This paralleled a significant rise in serum iron and transferrin saturation (TS) and a fall in E-ZPP and serum ferritin (baselines vs. 8 weeks, serum iron 68 ± 37 vs. 124 ± 64 μg/dl, TS 27 ± 10 vs. 48 ± 19%, E-ZPP 123 ± 44 vs. 70 ± 13 μmol/mol heme, and serum ferritin 816 ± 435 vs. 587 ± 323 μg/liter, P < 0.05). Compared with responders, mean values of hemoglobin, rEPO dose, iron metabolism parameters, and E-ZPP showed no significant changes in controls (N = 15) and in non-responders (N = 19). Thirty-seven patients (18 responders and 19 non-responders) were further analyzed by receiver operating characteristic curves to seek the critical for prediction of a response to IVAA treatment. The results showed that E-ZPP at a cut-off level of more than 105 μmol/mol heme and TS at a level of less than 25% were more specific to confirm the status of functional iron deficiency in iron-overloaded patients. The two criterion values had the highest accuracy to predict a response to treatment. Conclusions. Functional iron-deficient erythropoiesis plays a role in rEPO-hyporesponsive anemia in HD patients with hyperferritinemia. IVAA may be an adjuvant therapy for rEPO in these patients, and E-ZPP of more than 105 μmol/mol heme and TS of less than 25% should be used to guide the IVAA treatment.

Original languageEnglish
Pages (from-to)2477-2486
Number of pages10
JournalKidney International
Volume55
Issue number6
DOIs
StatePublished - 1999
Externally publishedYes

Keywords

  • Anemia
  • Dialysis
  • Erythropoiesis
  • Iron overload
  • Transferrin saturation
  • Zinc protoporphyrin

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