Hyporesponsiveness to Erythropoiesis Stimulating Agents in Chronic Kidney Disease: The Many Faces of Inflammation

The vast majority of patients with chronic kidney disease (CKD) receive an erythropoietic-stimulating agent (ESA) to partially correct the almost inevitable anemia associated with renal insufficiency. However, a minority of CKD patients will require much higher than usual doses of ESA in order to maintain a reasonable hemoglobin concentration. In many instances, these patients will have either an obvious or a clinically unapparent inflammatory process to account for the hyporesponsiveness to ESA replacement therapy. This review focuses on the mechanisms by which inflammation interferes with erythroid marrow function and particularly the new information about the role of inflammatory cytokines and the small peptide, hepcidin, on altered iron metabolism.