Considerations for optimal iron use for anemia due to chronic kidney disease

Availability of recombinant human erythropoietin (rHuEPO) has improved the treatment of anemia due to chronic kidney disease (CKD). Iron deficiency is the most common cause of resistance to rHuEPO therapy, contributing to ineffective erythropoiesis and hematocrit/hemoglobin values below the recommended target range (33%-36%/11-12 g/dL). I.v. iron supplementation is necessary to meet increased iron demands from stimulation of erythropoiesis and chronic blood loss; however, questions remain as to the optimal supplementation strategy to maintain appropriate yet safe iron status. Treatment guidelines for anemia management have been developed through the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI).

This review presents the basis of need for the NKF-K/DOQI guidelines and includes detailed information concerning iron physiology, metabolism, iron preparations, and evaluation of iron status.

This review was based on a MEDLINE search and complemented by references from the NKF-K/DOQI guidelines (whose review extended beyond MEDLINE). References focusing on normal iron physiology and metabolism, alterations in iron physiology in patients with CKD, laboratory evaluation methods, and strategies for iron supplementation were obtained from MEDLINE and reviewed for content.

Controversy over appropriate use of iron supplementation has led to disparity in accepted practice procedures. Oral iron (ferrous salts and polysaccharide iron complex) and i.v. iron preparations (iron dextran, sodium ferric gluconate, and iron sucrose) are available. Problems with oral iron supplementation include limited absorption and patient noncompliance. Although most available data on i.v. iron use in the United States are specific to iron dextran preparations, published information based on clinical use of sodium ferric gluconate and iron sucrose products has been promising. The use of chronic i.v. iron administration to sustain iron stores has been more widely accepted to prevent development of absolute and functional iron deficiency.

Although iron therapy is commonly warranted in patients with CKD, questions remain as to the most favorable supplementation strategy to optimize therapy through improvements in hematocrits, efficient use of rHuEPO, and maintenance of appropriate and safe iron levels. Clinicians will need to devise strategies based on the compilation of information from clinical experience and the available literature. Clinical practice guidelines devised by the NKF-K/DOQI have provided a useful tool for the medical community using both these resources.