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Effect of intravenous ascorbic acid in hemodialysis patients with EPO-hyporesponsive anemia and hyperferritinemia.
Am J Kidney Dis. 2006 Apr; 47(4):644-54.AJ

Abstract

BACKGROUND

Although erythropoietin (EPO)-hyporesponsive anemia in hemodialysis patients most commonly results from iron deficiency, the contributory role of chronic inflammation and oxidative stress in its pathogenesis is poorly understood. We conducted an open-label prospective study to assess the effect of vitamin C, an antioxidant, on EPO-hyporesponsive anemia in hemodialysis patients with unexplained hyperferritinemia.

METHODS

Forty-six of 262 patients in an inner-city hemodialysis center met the inclusion criteria (administration of intravenous iron and EPO for > or = 6 months at a dose > or = 450 U/kg/wk, average 3-month hemoglobin [Hb] level < or = 11.0 g/dL [< or = 110 g/L], ferritin level > or = 500 ng/mL (microg/L), and transferrin saturation [TSAT] < or = 50%). Patients were excluded if they had a clear explanation for the EPO hyporesponsiveness. Four patients refused to participate. The remaining patients were randomly assigned; 20 patients to receive standard care and 300 mg of intravenous vitamin C with each dialysis session (group 1) and 22 patients to receive standard care only (group 2). Study duration was 6 months. During the study, 1 patient from group 1 was removed (upper gastrointestinal bleeding) from final analysis. Monthly assessment included Hb level, mean corpuscular volume, iron level, iron-binding capacity, ferritin level, TSAT, and Hb content in reticulocytes. In addition, biointact parathyroid hormone, aluminum, C-reactive protein (CRP), and liver enzymes were measured every 3 months.

RESULTS

Age, sex, race, and time on dialysis therapy were similar in both groups. At 6 months, Hb levels significantly increased from 9.3 to 10.5 g/dL (93.0 to 105.0 g/L) in group 1, but not group 2 (9.3 to 9.6 g/dL [93.0 to 96.0 g/L]; P = 0.0001). Similarly, TSAT increased from 28.9% to 37.3% in group 1, but not group 2 (28.7% to 29.3%; P = 0.0001). EPO dose (477 to 429 versus 474 to 447 U/kg/wk), iron-binding capacity (216 to 194 versus 218 to 257 microg/dL [38.7 to 34.7 versus 39 to 46 micromol/L]), and CRP level (2.8 to 0.9 versus 2.8 to 2.2 mg/dL) decreased significantly in group 1, but not in controls. Changes in Hb content in reticulocytes and ferritin level also were statistically significant in group 1. There was no change in biointact parathyroid hormone levels. Although serum iron levels and intravenous iron doses changed within each group, changes were equal between the 2 groups.

CONCLUSION

In hemodialysis patients with refractory anemia and hyperferritinemia, vitamin C improved responsiveness to EPO, either by augmenting iron mobilization from its tissue stores or through antioxidant effects.

Authors+Show Affiliations

Division of Nephrology and Hypertension, Henry Ford Hospital, Detroit, MI 48202, USA. nattall1@hfhs.orgNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

16564942

Citation

Attallah, Nizar, et al. "Effect of Intravenous Ascorbic Acid in Hemodialysis Patients With EPO-hyporesponsive Anemia and Hyperferritinemia." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 47, no. 4, 2006, pp. 644-54.
Attallah N, Osman-Malik Y, Frinak S, et al. Effect of intravenous ascorbic acid in hemodialysis patients with EPO-hyporesponsive anemia and hyperferritinemia. Am J Kidney Dis. 2006;47(4):644-54.
Attallah, N., Osman-Malik, Y., Frinak, S., & Besarab, A. (2006). Effect of intravenous ascorbic acid in hemodialysis patients with EPO-hyporesponsive anemia and hyperferritinemia. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 47(4), 644-54.
Attallah N, et al. Effect of Intravenous Ascorbic Acid in Hemodialysis Patients With EPO-hyporesponsive Anemia and Hyperferritinemia. Am J Kidney Dis. 2006;47(4):644-54. PubMed PMID: 16564942.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of intravenous ascorbic acid in hemodialysis patients with EPO-hyporesponsive anemia and hyperferritinemia. AU - Attallah,Nizar, AU - Osman-Malik,Yahya, AU - Frinak,Stan, AU - Besarab,Anatole, PY - 2005/09/02/received PY - 2005/12/09/accepted PY - 2006/3/28/pubmed PY - 2006/5/24/medline PY - 2006/3/28/entrez SP - 644 EP - 54 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am J Kidney Dis VL - 47 IS - 4 N2 - BACKGROUND: Although erythropoietin (EPO)-hyporesponsive anemia in hemodialysis patients most commonly results from iron deficiency, the contributory role of chronic inflammation and oxidative stress in its pathogenesis is poorly understood. We conducted an open-label prospective study to assess the effect of vitamin C, an antioxidant, on EPO-hyporesponsive anemia in hemodialysis patients with unexplained hyperferritinemia. METHODS: Forty-six of 262 patients in an inner-city hemodialysis center met the inclusion criteria (administration of intravenous iron and EPO for > or = 6 months at a dose > or = 450 U/kg/wk, average 3-month hemoglobin [Hb] level < or = 11.0 g/dL [< or = 110 g/L], ferritin level > or = 500 ng/mL (microg/L), and transferrin saturation [TSAT] < or = 50%). Patients were excluded if they had a clear explanation for the EPO hyporesponsiveness. Four patients refused to participate. The remaining patients were randomly assigned; 20 patients to receive standard care and 300 mg of intravenous vitamin C with each dialysis session (group 1) and 22 patients to receive standard care only (group 2). Study duration was 6 months. During the study, 1 patient from group 1 was removed (upper gastrointestinal bleeding) from final analysis. Monthly assessment included Hb level, mean corpuscular volume, iron level, iron-binding capacity, ferritin level, TSAT, and Hb content in reticulocytes. In addition, biointact parathyroid hormone, aluminum, C-reactive protein (CRP), and liver enzymes were measured every 3 months. RESULTS: Age, sex, race, and time on dialysis therapy were similar in both groups. At 6 months, Hb levels significantly increased from 9.3 to 10.5 g/dL (93.0 to 105.0 g/L) in group 1, but not group 2 (9.3 to 9.6 g/dL [93.0 to 96.0 g/L]; P = 0.0001). Similarly, TSAT increased from 28.9% to 37.3% in group 1, but not group 2 (28.7% to 29.3%; P = 0.0001). EPO dose (477 to 429 versus 474 to 447 U/kg/wk), iron-binding capacity (216 to 194 versus 218 to 257 microg/dL [38.7 to 34.7 versus 39 to 46 micromol/L]), and CRP level (2.8 to 0.9 versus 2.8 to 2.2 mg/dL) decreased significantly in group 1, but not in controls. Changes in Hb content in reticulocytes and ferritin level also were statistically significant in group 1. There was no change in biointact parathyroid hormone levels. Although serum iron levels and intravenous iron doses changed within each group, changes were equal between the 2 groups. CONCLUSION: In hemodialysis patients with refractory anemia and hyperferritinemia, vitamin C improved responsiveness to EPO, either by augmenting iron mobilization from its tissue stores or through antioxidant effects. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/16564942/Effect_of_intravenous_ascorbic_acid_in_hemodialysis_patients_with_EPO_hyporesponsive_anemia_and_hyperferritinemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(05)01943-8 DB - PRIME DP - Unbound Medicine ER -