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Vol. 30. Issue. 3.May 2010
Pages 271-380
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Treatment with intravenous iron and ferritin level
Juan Fernández-Gallegoa, María Adoración Martína, Seema Sujana, Encarnacion Vegaa
a Servicio de Nefrología, Hospital Carlos Haya, Málaga, Málaga, España,
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 Dear Editor,  

 The 2006 K/DOQI guidelines on anaemia in patients on chronic haemodialysis (HD) indicate that treatment should be done with IV Fe in order to maintain a ferritin (FER) value of more than 200- 500μg/l to achieve adequate erythropoiesis.1 Other studies2,3 state that FER should be kept in a higher range, but there are no controlled studies comparing the efficacy as measured by the Hb, EPO dose, and iatrogenic sequelae4,5 in groups of patients with FER values above and below 500, with maximum values greater than 500 indicating high doses of IV Fe. Recent research shows that administration of low dose IV Fe on a continual basis causes increased protein oxidation, something that does not happen often with intermittent treatment.6  

 The purpose of this prospective observational case-control study is to evaluate, in 10 patients on HD, if the Hb and EPO dose changed with IV Fe administration in two different treatment protocols, lasting six months each. Patients were included after ruling out factors affecting erythropoiesis for six months before and during the study (transfusion, infection, inflammation, malnutrition, surgery, hospitalisation, severe hyperparathyroidism, etc.).  

 FER1 Protocol. Treated with 50mg Fe sucrose IV/1 HD session, 8 HD in a row (400mg) to achieve and maintain a maximum FER value greater than and close to 300μg/l; data collection six months before the start of the FER2 protocol.  

 FER2 Protocol. Treated with 25 mg Fe sucrose IV/1 weekly HD session for 16 weeks in a row (400mg) to achieve and maintain a maximum FER value greater than and close to 300μg/l; data collection from the fourth month of starting. FER was assessed, then 2 months to assess continued treatment in the two protocols, and we did not treat with IV Fe if there was an acute infection.  

 In each protocol we assessed: intact PTH/3 months, balanced KTV (Daugirdas)/month, albumin g/l/3 months, subjective global assessment of nutrition, PCR/3 months, Hb/month, EPO dose in units/kg/week, ferritin/2 months, total dose of IV Fe in mg/patient/6 months (Fe 6), total dose of IV Fe in mg/patient/1 month (Fe 1), range in mg/patient of Fe 6 (range Fe 6). Age (75 ± 12 years), female sex (40%), HD time in months and with vascular access, and high-flow membranes were similar. There was no statistically significant difference in PTH (268 ± 249, FER1 vs. 297 ± 198, FER2), eKTV (1.37 ± 0.1, FER1 vs. 1.34 ± 0.1, FER2), albumin (36.3 ± 3, FER1 versus 35.4 ± 3, FER2), mild malnutrition in both groups, CRP (11.4 ± 9, FER1 vs. 13 ± 11, FER2), or in the main variables: Hb (12.4 ± 0.4, FER1 versus 12.3 ± 0.3, FER2), EPO (99 ± 51, FER1 vs. 85 ± 46, FER2), Fe 6 (854 ± 204mg, FER1 vs. 598 ± 126, FER2), Fe 1 (142 ± 34mg, FER1 vs. 99 ± 21, FER2) and Fe 6 range (500- 1100mg, FER1 vs. 400 to 800mg, FER2), but there was a difference with p < 0.05 in FER (332 ± 24, FER1 vs. 225 ± 37, FER2).  

 This prospective observational casecontrol study of patients on HD shows that Hb, EPO dose, and dose of IV Fe administered with the two protocols (FER maximum range greater than and close to 300μg/l vs FER maximum value of less than and close to 300) do not change. Prior scientific evidence1,4 and data from this research suggest achieving adequate erythropoiesis when treating with IV Fe, reducing iatrogenic sequelae,4,5 and keeping the maximum FER greater than or less than and close to 300μg/l. Based on current evidence,6 it would be advisable to treat intermittently with low dose Fe.  

K/DOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease in adults: CPG and CPR 3.2: Using iron agents. Am J Kidney Dis. 2006.  47 (Suppl 3): S 58-S 70.
Coyne DW, Kapoian T, Suki W, Singh AK, Moran JE, Dahl NW, Rizkala AR, and the DRIVE STUDY GROUP: Ferric gluconate is highly efficacious in anemic hemodialysis patients with high serum ferritin and low transferrin saturation: Results of the dialysis patients response to IV iron with elevated ferritin (DRIVE) study. J Am Soc Nephrol. 2007.  18: 975-984. [Pubmed]
Singh AK, Coyne DW, Shapiro W, Rizkala AR, the DRIVE Study Group: Predictors of the response to treatment in anemic hemodialysis patients with high serum ferritin and low transferrin saturation. Kidney Int. 2007.  71: 1163-1171. [Pubmed]
Canavese C, Bergamo D, Ciccone G, Longo F, Fop F, Thea A, Martina G, Piga A: Validation of serum ferritin values by magnetic susceptometry in predicting iron overload in dialysis patients. Kidney Int. 2004. 65: 1091-1098. [Pubmed]
Bishu K, Agarwal R: Iron deficiency in the 2006 K/DOQI era: Acute injury with intravenous iron and concerns regarding long-term safety. Clin J Am Soc Nephrol. 2006. 1: (Suppl 1): S 19- S 23.
6.Anraku M, Kitamura K, Shintomo  R, Takeuchi K,Ikeda H, Nagano J, Ko T, Mera K, Tomita K, Otagiri M. Effect of intravenous iron administration frequency on AOPP and inflammatory biomarkers in chronic hemodialysis patients: A pilot study. Clin Biochem.2008.41: 1168-1174. [Pubmed]
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