Iron Metabolism in Chronic Kidney Disease Patients

Anemia is a common comorbidity in patients with chronic kidney disease (CKD) and occurs due to diminished renal function. The main cause of such anemia is decreased erythropoietin (EPO) production and secretion from the kidney and a lower erythropoietic response to EPO. Treatment therefore involves erythropoiesis-stimulating agents (ESAs). Optimal erythropoietic response to ESA therapy also requires adequate iron management. However, iron metabolism is also dysregulated in CKD patients.

During erythropoiesis, biomarkers of iron metabolism are dramatically altered by ESA therapy. Hepcidin 25 is a key hormone of iron metabolism that regulates iron absorption from the gut and the release of stored iron out of reticuloendothelial system cells. Recently, erythroferrone has been identified as an erythroid suppressor of hepcidin 25 production. Because erythroferrone levels are significantly increased by ESA treatment in CKD patients, it may be a key factor in facilitating the release of stored iron into the circulation during erythropoiesis in these patients. In this review, we discuss the characteristics of the important biomarkers of iron metabolism in CKD patients and the changes in these biomarkers after ESA administration. Key Messages: In CKD patients, the management of anemia with ESA therapy requires comprehensive assessment of the levels of various biomarkers, with consideration of their optimal and physiological levels during erythropoiesis.