Year : 2008 | Volume
: 19 | Issue : 6 | Page : 933--936
Effect of intravenous ascorbic acid in hemodialysis patients with anemia and hypeferritinemia
Keyhanian Shahrbanoo1, Omolbanin Taziki2,
1 Department of Oncology, Azad University of Tonekabon, Ramsar, Iran
2 Department of Nephrology, Mazandaran University of Medical Science, Sari, Iran
Department of Nephrology, Mazandaran University of Medical Science, Sari
Hemodialysis (HD) patients with functional iron deficiency (FID) often develop resistance to recombinant human erythropoietin (Epo). The contributory role of chronic inflammation and oxidative stress in its pathogenesis is poorly understood. We assessed the effect of vitamin C, an antioxidant, on Epo-hyporesponsive anemia in hemodialysis patients with unexplained hyperferritinemia levels. Thirty-one of 132 with Hb < 11 g/dL were prospectively followed up after exclusion of reasons for Epo hyporesponsiveness. Patients were randomly divided into two groups: 15 patients received standard care and 300 mg of intravenous vitamin C with each dialysis session (group 1) and 15 patients received standard care (group 2). After 3 months, Hb and transferrin saturation levels significantly increased in group 1 but not in group 2 (p < 0.05%). Hemoglobin content in reticulocyte and serum ferritin decreased significantly in group 1 but not in control group. In conclusion, hemodialysis patients with refractory anemia and adequate iron stores, vitamin C improved responsiveness to Epo by augmenting iron mobilization and possibly via antioxidant effect.
|How to cite this article:|
Shahrbanoo K, Taziki O. Effect of intravenous ascorbic acid in hemodialysis patients with anemia and hypeferritinemia.Saudi J Kidney Dis Transpl 2008;19:933-936
|How to cite this URL:|
Shahrbanoo K, Taziki O. Effect of intravenous ascorbic acid in hemodialysis patients with anemia and hypeferritinemia. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2021 Jan 27 ];19:933-936
Available from: https://www.sjkdt.org/text.asp?2008/19/6/933/43495
Anemia is a common complication of chronic renal failure. It is primarily due to insufficient secretion of Erythropoietin (Epo) from diseased kidneys. Recombinant Epo is useful in correction of anemia in renal failure and adequate response to Epo requires sufficient storage of accessible iron.  Improper response to Epo may be due to incomplete iron metabolism  even in the presence of adequate iron stores. This results in failure of iron utilization, characterized by high serum ferritin concentration and low transferrin saturation. ,,
Intravenous (IV) ascorbic acid (AA) in several studies improved Hb and iron availability in iron over-loaded, Epo-hyporesponsive hemodialysis patients. , Transferrin saturation of less than 25% and zinc protoporphyrin (zpp) of more than 105 Hmol/mol heme defined responders to IV AA, suggesting utility of these tests prior to therapy. ,
The aim of the present study was to compare the efficacy of IV AA in improving anemia and iron availability in hemodialysis patient with hyperferritinemia and hypo responsive to Epo.
Patients and Methods
This single blind clinical trial was performed in 2 medical centers (Ramsar and Tonekabon hospital) in Mazandaran province, Iran.
An open label prospective study of three months duration was conducted in 36 of 132 patients in an hemodialysis center fulfilling the inclusion criteria (administration of IV iron and Epo for > 3 months at least 6000 u/week, average 3 month hemoglobin level 12 and Epo three times a week.
Inter assay coefficient of variation for Hb, serum iron, serum ferritin, TIBC were less than 1.1, 5.4, 7.8 and 2.4, respectively.
The result was expressed as mean ± SE. Statistical analysis was performed using SPSS version 10.0. Independent T-Test was used to compare the results between groups at baseline, paired T-Test was used for within group comparison for pre and post treatment. P value p > 0.05 [Table 2]. After 3 month, Hb levels significantly increased from 8.5 to 9.6 in group 1, but not in (8.5 to 8.4) group 2 (p 12 or folate deficiency. ,
It seems that inadequate iron mobilization and defective iron utilization are important mechanisms of EPO hypo responsiveness. These patients have serum ferritin more than 100 mg, but cannot utilize iron in improving their anemia. 
Recent studies show that antioxidant effect of vitamin C can correct resistant anemia. ,
Tarng prescribed 300 mg i.v. AA to 46 hemodialysis patients with serum ferritin more than 500 mg/L and HCT  Hb increased from 8.8 to 10.7 and EPO dosage decreased by two third. In a cross over study by Keven et al, 63 hemodialysis patients, 500 mg of i.v. vitamin C or placebo three times a week resulted in the Hb increase by 1g/dL. 
Chest pain: (1 event), nausea: (2 events) and fatigue (2 events) compared to the control (no event). 
Similarly, Attallah showed that i.v. AA with each dialysis session increased Hb and TSAT in HD patients with refractory anemia and hyperferritinemia by improving responsiveness to EPO  .
Taji on the other hand did not find any beneficial effect of i.v. AA on anemia rather his patients experienced higher adverse events. 
Even hemodialysis patients with serum ferritin more than 300 mg/dL in hyporesponsive patients to EPO may still be considered as patients with iron deficiency,  it is not clear when to initiate treatment with vitamin C.
Finally, the limitations of our study include the smaller number of cases, treatment time, and EPO dose lower than others.
In conclusion, our study confirms that i.v. AA can improve functional iron deficiency in hemodialysis patients with refractory anemia. Further studies are needed to determine ferritin levels to start treatment with vitamin C for maximum response.
|1||Wingard RL, Parker RA, Ismail N, Hakim RM, Efficacy of oral iron therapy in patients receiving recombinant human rythropoietin. Am J Kidney Dis 1995;25.433-9.|
|2||Sunder-Plassmann G, Horl WH. Erythropoietin and iron. Clin Nephrol 1997;47(3):141-57.|
|3||Tarng DC, Huang TP, Chen TW, Yang WC. Erythropoietin hyporesponsiveness: from iron deficiency to iron overloaded. Kidney Int 1999;69:s107-18.|
|4||Tarng T, Haung T. A parallels, comparative study of intravenous iron versus intravenous Ascorbic Acid Erythropietin-hyporesponsive anemia in hemodialysis patients with iron overloaded. Nephrol Dial Transplant 1998;13: 2867-72|
|5||Tarng DC, Wei, YH, Huang TP, Kuo B, Yang W. Intravenous ascorbic acid as an adjuvant therapy for recombinant erythropoietin in hemodialysis patients with hyperferritinemia. Kidney Int 1999;55:2477-86.|
|6||Keven K, Kutlay S, Nergizoglu G, Erturk S. Randomized, crossover study of the effect of vitamin c on EPO response in hemodialysis patients. Am J Kidney Dis 2003;41:1233-9.|
|7||Adamson JW, Eschbach JW. Management of the anemia of chronic renal failure with recombinant human Erythropoietin. Q J Med New Seris 1989, 73: 1093-101.|
|8||Sezer S, Ozdemir FN, Yakupoglu U, Arat Z, Turan M, Haberal M. Intravenous ascorbic acid administration for erythropoietin hyporesponsive anemia in iron overloaded hemodialysis patients. Artif Organs 2002;26:366-70.|
|9||Lipschitz DA, Bothwell TH, Seftel HC, Wapnick AA, Charlton RW, the role of ascorbic acid in the metabolism of storage iron. Br J Haematol 1971;20:155-63.|
|10||Taji Y, Morimoto T, Okada K, Fukuhara S, Fukui T, Kuwahara T. Effect of intravenous ascorbic acid on erythropoiesis and quality of life in unselected hemodialysis patients. J Nephrology 2004;17(4):537-43.|
|11||Attallah N, Osmen-Malik Y, Frinak S, Besarab A. Effect of intravenous ascorbic acid in hemodialysis and hyperferritinemia. Am J Kidney Dis 2006;47(4):644-54.|
|12||National Kidney Foundation. K/ DOQI clinical practice guidelines for anemia of chronic kidney disease 2000. Am J kidney Dis 2001; 37:S182-38.|