Iron from dietary sources is inadequate to address functional iron deficiency associated with ESA use.

Anemia management in CKD patients remains an ongoing challenge for renal health professionals, especially regarding iron supplementation. “The goal of iron therapy in a patient with anemia and CKD is to achieve and maintain a target-range Hb [hemoglobin] level,” according to the National Kidney Foundation Kidney (NKF) Disease Outcomes Quality Initiative (KDOQI) clinical practice guidelines for anemia of CKD (Am J Kidney Dis. 2006;47[5 Suppl 3]:S11-S145).

Although iron stores measured as serum ferritin may indicate adequacy, functional iron deficiency is common with use of erythropoietin-stimulating agents (ESAs). Since iron from dietary sources (i.e., meat, poultry, certain vegetables, fortified bread and cereals) is insufficient to address functional iron deficiency, the KDOQI anemia guidelines recommend the use of iron supplements “as adjuvant therapy for those also undergoing treatment with an ESA.”

Oral vs. IV iron

Addressing the best method of iron administration for treating CKD anemia is a recent systematic review and meta-analysis by Rozen-Zvi et al (Am J Kidney Dis. 2008;52:897-906). The authors compared use of oral iron supplements vs. IV iron in 13 studies involving a total of 1,097 patients who had CKD stages 3-4 and stage 5 (mainly hemodialysis) with respect to improvement in hemoglobin level as well as all-cause mortality and adverse events.

Results indicated that, compared with oral iron, IV iron was associated with significantly better hemoglobin levels in dialysis patients and with a small though statistically significant benefit in stages 3 and 4 CKD. There was no difference in reported adverse events or mortality between IV and the author stresses that “it is important to bear in mind that IV iron should be withheld in case of active infection.” The author concludes that “the overall risk-benefit ratio favors the use of IV iron alone or with an ESA in the management of renal anemia” and that “clinical judgment is necessary in each individual to diagnose iron deficiency and effectively use IV iron.”

Oral iron supplements, while useful in earlier stages of CKD, have qualities that may limit their efficacy. A review of the clinical aspects of iron use in CKD (Hörl WH. J Am Soc Nephrol. 2007;18:382-393) details some drawbacks of oral supplementation, including GI complaints (constipation, diarrhea, abdominal discomfort), which can impact patient compliance; a newer iron compound, heme iron polypeptide (HIP), may be better tolerated.

Factors common to CKD patients that may interfere with the absorption of oral iron supplements include concomitant use of oral iron supplementation, though the authors note that follow-up data were limited to two to three months in the trials examined. Results of this meta-analysis support KDOQI recommendations that in hemodialysis patients, “the preferred route of administration is IV” and the opinion that in non-dialysis-dependent CKD (or peritoneal dialysis), “the route of iron administration can be either IV or oral.”