Iron Deficiency in CKD Without Concomitant Anemia

The physiological role of iron extends well beyond hematopoiesis. Likewise, the pathophysiological effects of iron deficiency (ID) extend beyond anemia. Although inextricably interrelated, ID and anemia of chronic kidney disease (CKD) are distinct clinical entities. For more than 3 decades, however, nephrologists have focused primarily on the correction of anemia. The achievement of target hemoglobin (Hgb) concentrations is prioritized over repletion of iron stores, and iron status is generally a secondary consideration only assessed in those patients with anemia. Historically, the correction of ID independent of anemia has not been a primary focus in the management of CKD. In contrast, ID is a key therapeutic target in the setting of heart failure (HF) with reduced ejection fraction (HFrEF); correction of ID in this population improves functional status and quality of life and may improve cardiovascular (CV) outcomes. Given the strong interrelationships between HF and CKD, it is reasonable to consider whether iron therapy alone may benefit those with CKD and evidence of ID irrespective of Hgb concentration. In this review, we differentiate anemia from ID by considering both epidemiologic and pathophysiological perspectives and by reviewing the evidence linking correction of ID to outcomes in patients with HF and/or CKD. Furthermore, we discuss existing gaps in evidence and provide proposals for future research and practical considerations for clinicians.