Work

Anemia of Chronic Disease Revisited: Hepcidin Dysregulation, Erythropoietic Failure, and Emerging Roles of SGLT2 Inhibition

Year: 2026

Type: article

Abstract: Anemia of chronic disease (ACD), also referred to as anemia of inflammation, is a prevalent and clinically significant complication of chronic infection, autoimmune disease, malignancy, and chronic kidney disease. It is characterized by inflammation-driven iron sequestration, impaired erythropoietin (EPO) production and signaling, and suppression of effective erythropoiesis. Current therapies (iron supplementation and erythropoiesis-stimulating agents) often address downstream consequences and may be limited by hepcidin-driven functional iron deficiency, cytokine-mediated EPO resistance, and safety concerns in vulnerable populations. This review re-examines ACD through an integrated framework of hepcidin dysregulation, iron sequestration, and inflammatory inhibition of the EPO axis. We then synthesize emerging evidence that sodium-glucose cotransporter 2 (SGLT2) inhibitors produce sustained increases in hemoglobin/hematocrit beyond transient hemoconcentration across cardiovascular and kidney disease trials, including in non-diabetic populations. Mechanistic studies suggest a coordinated biologic response that may include reduced hepcidin, improved iron mobilization, physiologic augmentation of endogenous EPO, and attenuation of systemic inflammation-pathways directly relevant to ACD. We critically re-appraise current ACD paradigms by contrasting downstream "replacement" strategies (iron and ESAs) with pathway-level approaches (HIF-PHIs and SGLT2 inhibition), and we outline biomarker-guided study designs to test whether SGLT2 inhibition may act as an adjunctive physiologic modulator of iron-erythropoietic crosstalk in well-phenotyped inflammatory anemia cohorts, while emphasizing that current evidence remains hypothesis-generating rather than practice-changing.

Source: European Journal Of Haematology

DOI: 10.1111/ejh.70197

Authors: Mohammed Abdulgayoom, Awni Alshurafa, Rasha Kaddoura, Abdulrahman F. Al‐Mashdali, Shehab F. Mohamed, Mohamed A. Yassin

Institutions: National Center for Cancer Care and Research, Hamad Medical Corporation

Language: English

Topic: Erythropoietin and Anemia Treatment

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,650