Iron deficiency anemia can worsen clinical outcomes, increase disability, and contribute to poor quality of life for patients with chronic kidney disease (CKD). Now a new systematic review published in the European Journal of Internal Medicine confirms foundational advice on evaluating and treating CKD patients for microcytic anemia.

Lucia De Franceschi, MD, of University of Verona in Verona, Italy, and colleagues performed a focused review of recently published (2010 to 2016), high-quality literature on the subject, including randomized clinical trials, meta-analyses, systematic reviews, clinical guidelines, and scientific society recommendations. Based on the evidence, the investigators confirmed that serum ferritin and transferrin saturation are the most valuable blood tests for diagnosis of anemia. During follow-up, the percentage of hypochromic red cells and reticulocyte hemoglobin content may be useful.

The reviewers emphasized the importance of an initial comprehensive patient history and evaluation and assessment of treatment costs relative to benefits. C-reactive protein should be measured to rule out inflammation due to a co-existing disease. Through testing, clinicians can determine when there is an absolute iron deficiency from depleted iron stores or a functional iron deficiency affecting iron mobilization. They also pointed out some interesting, but as yet unproven tests, including soluble transferrin receptor (sTfR) and sTfR-ferritin for identifying iron deficiency anemia in the presence of inflammation that affects serum ferritin levels. In addition, measuring Hamp serum levels may aid diagnosis of iron-refractory iron-deficiency anemia.

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The investigators confirmed that hemoglobin levels should guide treatment. Oral iron supplementation is suggested for non-dialysis CKD patients not receiving erythropoiesis-stimulating agents (ESAs). Intravenous (IV) iron should be strongly considered for patients treated with ESAs or hemodialysis because oral iron is inadequate for ESA-stimulated erythropoiesis. Newer intravenous iron formulations may provide quicker iron repletion.

Whether to use high-dose iron less frequently or low-dose iron remains debatable. For some, it is important to rapidly resolve the iron deficiency. To avoid iron overload, serum ferritin, transferrin saturation, and hemoglobin levels should be routinely checked, especially in CKD patients receiving IV iron long term.

The researchers emphasized that microcytic anemia in patients with end-stage renal disease is complex. It may result from reduced intestinal iron absorption and chronic inflammation. The iron deficiency can hinder endogenous erythropoietin production and response to ESAs.

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De Franceschi L, Iolascon A, Taher A, Cappellini MD. Clinical management of iron deficiency anemia in adults: systemic review on advances in diagnosis and treatment. Eur J Intern Med. May 18, 2017. pii: S0953-6205(17)30165-6. doi: 10.1016/j.ejim.2017.04.018 [Epub ahead of print]