Intravenous Versus Oral Iron for Treatment of Iron Deficiency in Non-hemodialysis-dependent Patients With Chronic Kidney Disease

Anne Marie Liles


Am J Health Syst Pharm. 2012;69(14):1206-1211. 

In This Article


Interpretation of the results of these studies is limited by several factors, the most significant of which is short study duration, ranging from 21 days to six months. ND-CKD patients, especially those receiving ESAs, will likely require long-term treatment with oral iron or periodic i.v. iron infusions throughout the course of the disease. Increases in hemoglobin values after oral iron intake are typically seen in four to eight weeks; however, repletion of iron stores generally requires an additional three to six months or longer.[22] Despite three studies that found no significant difference in hemoglobin values with i.v. and oral iron therapy, all found a significantly greater increase in ferritin or TSAT with i.v. iron.[11,17,21] It is unknown whether this difference would persist if patients were treated with oral iron for a longer duration. Two studies that found i.v. iron to be superior did report significant increases in hemoglobin values from baseline with oral iron;[16,18] however, it is unknown if long-term treatment would eventually result in a negative iron balance and thus a decrease in hemoglobin concentration.

While adverse effects were reported, the short duration of the studies limited the ability to evaluate long-term effects. Studies showing increased oxidative stress with the use of i.v. iron have suggested that repeated treatment with i.v. iron may lead to atherosclerosis, endothelial dysfunction, and renal injury.[23,24] These studies have identified bio-markers of oxidative stress but have not evaluated clinical outcomes. Long-term effects of i.v. versus oral iron cannot be evaluated from the studies reviewed.

Most of the trials included patients receiving treatment with an ESA. While some investigators tried to control for this by including only patients on stable dosages, this confounder makes it difficult to see the true effect of iron on hemoglobin and iron laboratory values. It is possible that in studies finding increases in hemoglobin values but either no change or decreases in iron stores with oral iron, the effect may have been due to the ESA. However, the inclusion of patients treated with ESAs is more reflective of actual clinical practice with the ND-CKD population. In the only trial comparing ESA dosage requirements in ND-CKD patients treated with oral or i.v. iron, Stoves et al.[11] found no difference in hemoglobin values between the groups, supporting the two additional trials that found no significant difference in hemoglobin concentrations between oral and i.v. iron groups;[17,21] however, there are no trials confirming or refuting these data.

The argument could be made that because i.v. iron has consistently been associated with improvements in serum iron markers, it is superior to oral iron. However, a recently published study by Ferrari et al.[25] questioned the utility of serum iron markers in guiding iron repletion in ND-CKD patients. When comparing serum iron laboratory values (TSAT and ferritin) to liver iron concentration in ND-CKD patients after the administration of a single high dose of i.v. iron, only liver iron concentration had a consistent dose-dependent response. The results suggest that increases in iron in the body may not be reflected in traditional serum iron laboratory values. Therefore, when reviewing the data comparing oral and i.v. iron, it appears that the serum hemoglobin value is a better indicator of treatment efficacy deficiency.

Small study populations also make it difficult to rule out a possible Type II error. In 2008, Rozen-Zvi et al.[26] conducted a meta-analysis that included six studies reviewed herein. The authors found a significantly greater increase in hemoglobin concentration with i.v. iron versus oral iron (weighted mean difference, 0.31 g/dL; 95% confidence interval, 0.09–0.53), but this small difference could be viewed as clinically insignificant.


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