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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2008  |  Volume : 19  |  Issue : 6  |  Page : 933-936
Effect of intravenous ascorbic acid in hemodialysis patients with anemia and hypeferritinemia

1 Department of Oncology, Azad University of Tonekabon, Ramsar, Iran
2 Department of Nephrology, Mazandaran University of Medical Science, Sari, Iran

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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.

Keywords: Erythropoietin, Anemia, Hyperferritinemia, Vitamin C

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;19:933-6

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 Dec 2];19:933-6. Available from: https://www.sjkdt.org/text.asp?2008/19/6/933/43495

   Introduction Top

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. [1] Improper response to Epo may be due to incomplete iron metabolism [2] 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. [3],[4],[5]

Intravenous (IV) ascorbic acid (AA) in seve­ral studies improved Hb and iron availability in iron over-loaded, Epo-hyporesponsive hemo­dialysis patients. [4],[6] 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. [2],[4]

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 Top

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 < 11 g/dL, ferritin level ≥ 300 ng/mL and T saturation (TSAT) < 30%. The patients were excluded if they had a clear explanation for the Epo-hypo­responsiveness such as acute infection, active liver disease, bleeding, acute ischemia and symp­tomatic heart failure.

Blood samples for measurement of Hb, HCT, and MCV, serum iron, ferritin and TIBC. TSAT (Fe/TIBC × 100) were obtained after baseline and at the end of study after three months. Patients were randomly divided into two groups.

15 patients received standard care and 300 mg of IV AA with each dialysis session (group 1) and 16 patients received standard care only (group 2). During the study all patients' re­ceived, folic acid, vitaminB 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.

   Statistical analysis Top

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 < 0.05 was considered significant.

   Result Top

31 of the 36 randomized patients completed the study, 15 patients in group 1 and 16 pa­tients in group 2. The remaining 5 patients could not complete the study due to death (n=2) and blood transfusion after randomiza­tion (n=3).

Both groups were similar in clinical characte­ristics [Table 1]. All women had amenorrhea. All of patients dialyzed 4 hours, 3 times a week with similar kt/V.

Hb, serum iron, serum ferritin and TSAT was similar in the two groups at baseline, 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 < 0.05). Similarly, TSAT increased in group 1.

Iron binding capacity (and Ferritin [Table 2] and CRP level (data not shown) decreased significantly in group 1 only.

   Discussion Top

In this study Hb increased in group 1 but not in the control group. After 3 months of treat­ment with i.v. AA, T sat increased and serum ferritin significantly decreased in i.v. AA group.

Hemodialysis patients with anemia may res­pond inadequately to EPO due to iron defi­ciency, inflammation, vitamin B 12 or folate deficiency. [7],[8]

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. [9]

Recent studies show that antioxidant effect of vitamin C can correct resistant anemia. [4],[6]

Tarng prescribed 300 mg i.v. AA to 46 hemo­dialysis patients with serum ferritin more than 500 mg/L and HCT < 30%, three times a week for two months. [5] 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. [6]

Chest pain: (1 event), nausea: (2 events) and fatigue (2 events) compared to the control (no event). [10]

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 [10] .

Taji on the other hand did not find any bene­ficial effect of i.v. AA on anemia rather his patients experienced higher adverse events. [11]

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, [12] 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.

   References Top

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.  Back to cited text no. 1    
2.Sunder-Plassmann G, Horl WH. Erythropoietin and iron. Clin Nephrol 1997;47(3):141-57.  Back to cited text no. 2    
3.Tarng DC, Huang TP, Chen TW, Yang WC. Erythropoietin hyporesponsiveness: from iron deficiency to iron overloaded. Kidney Int 1999;69:s107-18.  Back to cited text no. 3    
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  Back to cited text no. 4    
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.  Back to cited text no. 5    
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.  Back to cited text no. 6    
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.  Back to cited text no. 7    
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.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
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.  Back to cited text no. 9    
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.  Back to cited text no. 10    
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.  Back to cited text no. 11    
12.National Kidney Foundation. K/ DOQI clinical practice guidelines for anemia of chronic kidney disease 2000. Am J kidney Dis 2001; 37:S182-38.  Back to cited text no. 12    

Correspondence Address:
Omolbanin Taziki
Department of Nephrology, Mazandaran University of Medical Science, Sari
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PMID: 18974579

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