Iron Management in Chronic Kidney Disease

Chronic kidney disease (CKD) is frequently complicated by anaemia arising from impaired erythropoietin production, systemic inflammation and disrupted iron homeostasis. Inflammatory signals drive hepatic hepcidin synthesis, which sequesters iron and limits its absorption and release, exacerbating iron-restricted erythropoiesis. Clinicians monitor iron status primarily through serum ferritin, reflecting storage, and transferrin saturation (TSAT), indicating circulating availability. Both iron deficiency and overload carry risks in CKD: insufficient iron worsens anaemia and quality of life, whereas excess iron may promote oxidative stress, vascular calcification and cardiovascular events. Management strategies encompass oral and intravenous iron supplementation, often alongside erythropoiesis-stimulating agents (ESAs), balanced against potential thrombotic and inflammatory complications. Emerging therapies targeting the hypoxia-inducible factor (HIF) pathway offer new avenues to optimise physiological erythropoiesis and iron utilisation. Effective iron management in CKD demands precise assessment, individualised dosing and vigilance for adverse outcomes, underscoring its global public-health importance.

Research from Nature Portfolio

Recent studies have clarified the dual risks of iron biomarkers in CKD progression. A large prospective cohort investigation found that both low and high serum ferritin quartiles were independently associated with accelerated decline in renal function, progression to end-stage kidney disease and death due to kidney failure. This U-shaped relationship emphasises the need for narrowly defined target ranges of ferritin and TSAT to mitigate risk. Experimental research on human aortic vascular smooth muscle cells has revealed that iron loading stimulates calcification through up-regulation of interleukin-24, providing mechanistic insight into how iron overload contributes to vascular complications commonly observed in CKD patients.

Iron Management in Chronic Kidney Disease publication trend

The graph below shows the total number of articles in iron management in chronic kidney disease across all publications each year (not limited to Nature Index journals).

Technical terms

Chronic kidney disease (CKD): A progressive loss of renal function impairing waste excretion and endocrine regulation.

Ferritin: An intracellular protein complex that stores iron; serum concentration indicates total body iron reserves.

Transferrin saturation (TSAT): The percentage of iron-binding sites on transferrin occupied by iron; reflects circulating iron availability.

Hepcidin: A liver-derived peptide hormone that down-regulates iron export by binding ferroportin and causing its internalisation.

Erythropoiesis-stimulating agents (ESAs): Exogenous glycoproteins that mimic erythropoietin to stimulate red-blood-cell production in CKD-associated anaemia.

HIF-PH inhibitors: Small molecules that stabilise hypoxia-inducible factor, promoting endogenous erythropoietin synthesis and improved iron handling.

References

1. Impact of Inflammation on Ferritin, Hepcidin and the Management of Iron Deficiency Anemia in Chronic Kidney Disease. Nutrients (2018).
2. Association between iron status markers and kidney outcome in patients with chronic kidney disease. Scientific Reports (2023).
3. Iron-induced calcification in human aortic vascular smooth muscle cells through interleukin-24 (IL-24), with/without TNF-alpha. Scientific Reports (2018).
4. Treatment of Anemia Associated with Chronic Kidney Disease: Plea for Considering Physiological Erythropoiesis. International Journal of Molecular Sciences (2024).
5. Association of oral iron replacement therapy with kidney failure and mortality in CKD patients. Clinical Kidney Journal (2023).
6. Elevated Ferritin Levels Associated with High Body Fat Mass Affect Mortality in Peritoneal Dialysis Patients. Nutrients (2023).